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European Commission approves first CAR T-cell therapies
The , two chimeric antigen receptor (CAR) T-cell therapies.
Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.
The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).
The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
The , two chimeric antigen receptor (CAR) T-cell therapies.
Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.
The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).
The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
The , two chimeric antigen receptor (CAR) T-cell therapies.
Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.
The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).
The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
EC approves CAR T-cell therapy for ALL, DLBCL
The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy targeting CD19.
Tisagenlecleucel (formerly CTL019) is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
The EC’s approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
JULIET trial
Updated results from JULIET were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).
The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so due to disease progression or clinical deterioration. The patients’ median age at baseline was 56 (range, 22-76).
Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached.
At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
For all infused patients (n=111), the 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Fifteen percent of patients received tocilizumab for CRS, including 3% of patients with grade 2 CRS and 50% of patients with grade 3 CRS.
Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).
ELIANA trial
Updated results from ELIANA were published in NEJM in February.
The trial included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).
All 75 patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.
The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to transplant while in remission. At last follow-up, 4 were still in remission, and 4 had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
All patients experienced at least one AE, and 95% had AEs thought to be related to tisagenlecleucel. The rate of grade 3/4 AEs was 88%, and the rate of related grade 3/4 AEs was 73%.
AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).
The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy targeting CD19.
Tisagenlecleucel (formerly CTL019) is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
The EC’s approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
JULIET trial
Updated results from JULIET were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).
The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so due to disease progression or clinical deterioration. The patients’ median age at baseline was 56 (range, 22-76).
Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached.
At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
For all infused patients (n=111), the 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Fifteen percent of patients received tocilizumab for CRS, including 3% of patients with grade 2 CRS and 50% of patients with grade 3 CRS.
Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).
ELIANA trial
Updated results from ELIANA were published in NEJM in February.
The trial included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).
All 75 patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.
The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to transplant while in remission. At last follow-up, 4 were still in remission, and 4 had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
All patients experienced at least one AE, and 95% had AEs thought to be related to tisagenlecleucel. The rate of grade 3/4 AEs was 88%, and the rate of related grade 3/4 AEs was 73%.
AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).
The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah®), a chimeric antigen receptor (CAR) T-cell therapy targeting CD19.
Tisagenlecleucel (formerly CTL019) is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
The EC’s approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
JULIET trial
Updated results from JULIET were presented at the 23rd Annual Congress of the European Hematology Association in June (abstract S799).
The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so due to disease progression or clinical deterioration. The patients’ median age at baseline was 56 (range, 22-76).
Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. The median duration of response was not reached.
At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
For all infused patients (n=111), the 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Fifteen percent of patients received tocilizumab for CRS, including 3% of patients with grade 2 CRS and 50% of patients with grade 3 CRS.
Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).
ELIANA trial
Updated results from ELIANA were published in NEJM in February.
The trial included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).
All 75 patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.
The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to transplant while in remission. At last follow-up, 4 were still in remission, and 4 had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
All patients experienced at least one AE, and 95% had AEs thought to be related to tisagenlecleucel. The rate of grade 3/4 AEs was 88%, and the rate of related grade 3/4 AEs was 73%.
AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).
Could An Antibiotic Be the Next Great Oncologic Drug?
An antibiotic drug used to treat acne, among other things, may turn out to have potential well beyond that. Researchers from University of Antioquiain Medellin, Colombia, suggest that minocycline could be a promising antileukemic drug.
Minocycline is a well-established tetracycline derivative, used clinically since 1971, with a safe track record. But it also has nonantibiotic properties, exerting both antioxidant and antiapoptotic effects. There is even “compelling” preclinical evidence, the researchers say, that minocycline induces apoptosis in an acute myeloid leukemia cell line and a chronic myeloid leukemia cell line. Would the same be true of acute lymphoblastic leukemia (ALL) cells? To test their hypothesis, the researchers examined minocycline’s mechanism of action in the Jurkat cell line, an ALL tumor line established in the 1970s from the peripheral blood of a 14-year-old boy.
The researchers found that minocycline did in fact induce apoptosis in Jurkat cells through a hydrogen peroxide (H2O2)-mediated signaling pathway. Indeed, they add, H2O2 triggers a whole cascade of adverse effects, including up-regulation of pro-apoptotic proteins. The researchers suggest that minocycline might even be capable of generating H2O2, which could explain the cytotoxic effects not only of minocycline, but of other tetracycline analogues. “Interestingly,” the researchers say, minocycline did all that without inducing oxidative stress or apoptosis makers in human peripheral blood lymphocyte cells.
The significance of their study is twofold, the researchers say: First, that minocycline is a safe and specific apoptosis-inducing drug against Jurkat cells in vitro; second, that it is pharmacologically well characterized and widely available.
The researchers note that no information is available on whether minocycline might efficiently kill ALL cells in vivo. However, they also note that minocycline has been found to be safe and well tolerated in doses up to 10 mg/kg in stroke patients—a dose that could be a sufficient concentration to reduce the viability of leukemia cell lines.
Source:
Ruiz-Moreno C, Velez-Pardo C, Jimenez-Del-Rio M. Toxicol In Vitro. 2018;50:336-346.
doi: 10.1016/j.tiv.2018.03.012
An antibiotic drug used to treat acne, among other things, may turn out to have potential well beyond that. Researchers from University of Antioquiain Medellin, Colombia, suggest that minocycline could be a promising antileukemic drug.
Minocycline is a well-established tetracycline derivative, used clinically since 1971, with a safe track record. But it also has nonantibiotic properties, exerting both antioxidant and antiapoptotic effects. There is even “compelling” preclinical evidence, the researchers say, that minocycline induces apoptosis in an acute myeloid leukemia cell line and a chronic myeloid leukemia cell line. Would the same be true of acute lymphoblastic leukemia (ALL) cells? To test their hypothesis, the researchers examined minocycline’s mechanism of action in the Jurkat cell line, an ALL tumor line established in the 1970s from the peripheral blood of a 14-year-old boy.
The researchers found that minocycline did in fact induce apoptosis in Jurkat cells through a hydrogen peroxide (H2O2)-mediated signaling pathway. Indeed, they add, H2O2 triggers a whole cascade of adverse effects, including up-regulation of pro-apoptotic proteins. The researchers suggest that minocycline might even be capable of generating H2O2, which could explain the cytotoxic effects not only of minocycline, but of other tetracycline analogues. “Interestingly,” the researchers say, minocycline did all that without inducing oxidative stress or apoptosis makers in human peripheral blood lymphocyte cells.
The significance of their study is twofold, the researchers say: First, that minocycline is a safe and specific apoptosis-inducing drug against Jurkat cells in vitro; second, that it is pharmacologically well characterized and widely available.
The researchers note that no information is available on whether minocycline might efficiently kill ALL cells in vivo. However, they also note that minocycline has been found to be safe and well tolerated in doses up to 10 mg/kg in stroke patients—a dose that could be a sufficient concentration to reduce the viability of leukemia cell lines.
Source:
Ruiz-Moreno C, Velez-Pardo C, Jimenez-Del-Rio M. Toxicol In Vitro. 2018;50:336-346.
doi: 10.1016/j.tiv.2018.03.012
An antibiotic drug used to treat acne, among other things, may turn out to have potential well beyond that. Researchers from University of Antioquiain Medellin, Colombia, suggest that minocycline could be a promising antileukemic drug.
Minocycline is a well-established tetracycline derivative, used clinically since 1971, with a safe track record. But it also has nonantibiotic properties, exerting both antioxidant and antiapoptotic effects. There is even “compelling” preclinical evidence, the researchers say, that minocycline induces apoptosis in an acute myeloid leukemia cell line and a chronic myeloid leukemia cell line. Would the same be true of acute lymphoblastic leukemia (ALL) cells? To test their hypothesis, the researchers examined minocycline’s mechanism of action in the Jurkat cell line, an ALL tumor line established in the 1970s from the peripheral blood of a 14-year-old boy.
The researchers found that minocycline did in fact induce apoptosis in Jurkat cells through a hydrogen peroxide (H2O2)-mediated signaling pathway. Indeed, they add, H2O2 triggers a whole cascade of adverse effects, including up-regulation of pro-apoptotic proteins. The researchers suggest that minocycline might even be capable of generating H2O2, which could explain the cytotoxic effects not only of minocycline, but of other tetracycline analogues. “Interestingly,” the researchers say, minocycline did all that without inducing oxidative stress or apoptosis makers in human peripheral blood lymphocyte cells.
The significance of their study is twofold, the researchers say: First, that minocycline is a safe and specific apoptosis-inducing drug against Jurkat cells in vitro; second, that it is pharmacologically well characterized and widely available.
The researchers note that no information is available on whether minocycline might efficiently kill ALL cells in vivo. However, they also note that minocycline has been found to be safe and well tolerated in doses up to 10 mg/kg in stroke patients—a dose that could be a sufficient concentration to reduce the viability of leukemia cell lines.
Source:
Ruiz-Moreno C, Velez-Pardo C, Jimenez-Del-Rio M. Toxicol In Vitro. 2018;50:336-346.
doi: 10.1016/j.tiv.2018.03.012
Role of SES in childhood cancer survival disparities
Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.
The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.
SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).
Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.
The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.
The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.
Survival differences by race/ethnicity
The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.
| Survival—black vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.43 | 1.15-1.77 | <0.01 |
| AML | 1.68 | 1.36-2.07 | <0.001 |
| Neuroblastoma | 1.38 | 1.08-1.75 | 0.01 |
| NHL | 1.53 | 1.14-2.07 | 0.01 |
| Hodgkin lymphoma | 1.66 | 1.06-2.60 | 0.03 |
| Astrocytoma | 1.95 | 1.57-2.43 | <0.001 |
| Non-astrocytoma CNS tumor | 1.53 | 1.25-1.88 | <0.001 |
| Non-rhabdomyosarcoma STS | 1.40 | 1.06-1.84 | 0.02 |
| Rhabdomyosarcoma | 1.44 | 1.10-1.88 | 0.01 |
In addition, whites had a significant survival advantage over Hispanics for the following cancers.
| Survival—Hispanic vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.63 | 1.43-1.86 | <0.001 |
| Neuroblastoma | 1.31 | 1.04-1.65 | 0.02 |
| NHL | 1.65 | 1.29-2.12 | <0.001 |
| Astrocytoma | 1.34 | 1.10-1.64 | <0.01 |
| Wilms tumor | 1.60 | 1.04-2.45 | 0.03 |
| Germ cell tumor | 1.63 | 1.19-2.24 | <0.01 |
Impact of SES
SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.
For black versus white patients, SES reduced the original association between race/ethnicity and survival by:
- 44% for ALL
- 28% for AML
- 49% for neuroblastoma
- 34% for NHL.
For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:
- 31% for ALL
- 73% for AML
- 48% for neuroblastoma
- 28% for NHL.
“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.
“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”
This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.
Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.
The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.
SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).
Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.
The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.
The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.
Survival differences by race/ethnicity
The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.
| Survival—black vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.43 | 1.15-1.77 | <0.01 |
| AML | 1.68 | 1.36-2.07 | <0.001 |
| Neuroblastoma | 1.38 | 1.08-1.75 | 0.01 |
| NHL | 1.53 | 1.14-2.07 | 0.01 |
| Hodgkin lymphoma | 1.66 | 1.06-2.60 | 0.03 |
| Astrocytoma | 1.95 | 1.57-2.43 | <0.001 |
| Non-astrocytoma CNS tumor | 1.53 | 1.25-1.88 | <0.001 |
| Non-rhabdomyosarcoma STS | 1.40 | 1.06-1.84 | 0.02 |
| Rhabdomyosarcoma | 1.44 | 1.10-1.88 | 0.01 |
In addition, whites had a significant survival advantage over Hispanics for the following cancers.
| Survival—Hispanic vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.63 | 1.43-1.86 | <0.001 |
| Neuroblastoma | 1.31 | 1.04-1.65 | 0.02 |
| NHL | 1.65 | 1.29-2.12 | <0.001 |
| Astrocytoma | 1.34 | 1.10-1.64 | <0.01 |
| Wilms tumor | 1.60 | 1.04-2.45 | 0.03 |
| Germ cell tumor | 1.63 | 1.19-2.24 | <0.01 |
Impact of SES
SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.
For black versus white patients, SES reduced the original association between race/ethnicity and survival by:
- 44% for ALL
- 28% for AML
- 49% for neuroblastoma
- 34% for NHL.
For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:
- 31% for ALL
- 73% for AML
- 48% for neuroblastoma
- 28% for NHL.
“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.
“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”
This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.
Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.
The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.
SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).
Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.
The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.
The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.
Survival differences by race/ethnicity
The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.
| Survival—black vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.43 | 1.15-1.77 | <0.01 |
| AML | 1.68 | 1.36-2.07 | <0.001 |
| Neuroblastoma | 1.38 | 1.08-1.75 | 0.01 |
| NHL | 1.53 | 1.14-2.07 | 0.01 |
| Hodgkin lymphoma | 1.66 | 1.06-2.60 | 0.03 |
| Astrocytoma | 1.95 | 1.57-2.43 | <0.001 |
| Non-astrocytoma CNS tumor | 1.53 | 1.25-1.88 | <0.001 |
| Non-rhabdomyosarcoma STS | 1.40 | 1.06-1.84 | 0.02 |
| Rhabdomyosarcoma | 1.44 | 1.10-1.88 | 0.01 |
In addition, whites had a significant survival advantage over Hispanics for the following cancers.
| Survival—Hispanic vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.63 | 1.43-1.86 | <0.001 |
| Neuroblastoma | 1.31 | 1.04-1.65 | 0.02 |
| NHL | 1.65 | 1.29-2.12 | <0.001 |
| Astrocytoma | 1.34 | 1.10-1.64 | <0.01 |
| Wilms tumor | 1.60 | 1.04-2.45 | 0.03 |
| Germ cell tumor | 1.63 | 1.19-2.24 | <0.01 |
Impact of SES
SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.
For black versus white patients, SES reduced the original association between race/ethnicity and survival by:
- 44% for ALL
- 28% for AML
- 49% for neuroblastoma
- 34% for NHL.
For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:
- 31% for ALL
- 73% for AML
- 48% for neuroblastoma
- 28% for NHL.
“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.
“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”
This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.
Groups release guidelines for CAR T treatment in children
emphasize the need for a flexible approach to detect early signs of serious complications for younger patients treated with this emerging class of medicines.
Researchers at the University of Texas MD Anderson Cancer Center, Houston, and the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) developed the guidelines, which were published in Nature Reviews Clinical Oncology. The recommendations build on the guidelines for more general use of these medicines from MD Anderson’s CARTOX Program, which Nature Reviews Clinical Oncology published in 2017.
Among the chief concerns with this new class of medicines are cytokine-release syndrome (CRS) and CAR T cell-related encephalopathy syndrome (CRES), according to Kris Michael Mahadeo, MD MPH, of the MD Anderson Cancer Center and his coauthors of the new paper.
Some of the tools used for older patients in screening for complications with CAR T drugs don’t work as well with younger ones, Dr. Mahadeo said in an interview. For instance, at MD Anderson, a handwriting sample is used to monitor patients for CAR T cell-related encephalopathy syndrome, which has symptoms of confusion and delirium. Patients provide a baseline handwriting sample of a single sentence that’s scanned into the medical record, and then they are asked to write this again during their time in the hospital, he said. But this tool may not work for children too young to write well.
The new guidelines suggest using the Cornell Assessment of Pediatric Delirium (CAPD) or to evaluate a child’s mental state, asking questions about eye contact, and level of awareness and mood, Dr. Mahadeo said. An alternative for patients aged 12 years and older with greater cognitive ability is the CARTOX-10 grading system.
“The nurses who spent most of the day with these patients will observe them over their shift and kind of get an idea of what was normal and answer a series of questions” through the CAPD tool, which is already used in ICUs, Dr. Mahadeo said. “It takes into consideration both the nurses’ perception and the parents, or whoever is at the bedside with the child. So that if they have a concern, it gives them a point that actually escalates things upward.”
The newly published recommendations also remind physicians and others caring for young patients to pay attention to these reports.
“Parent and/or caregiver concerns should be addressed because early signs or symptoms of CRS can be subtle and best recognized by those who know the child best,” Dr. Mahadeo and his colleagues wrote in a summary of key recommendations in the paper.
The recommendations also noted a need for close monitoring for complications such as hypotension, hypocalcemia, and catheter-related pain in young patients who require a leukapheresis catheter for cell collection. Infant and younger children “might not verbalize these symptoms,” according to the researchers.
Other recommendations include:
- Obtaining the child’s assent when appropriate, with psychological services often aiding in this goal. Dr. Mahadeo and his colleagues recommend considering “age-appropriate advance directives.”
- Maintaining high vigilance for sinus tachycardia as an early sign of CRS, using age-specific normal range or baseline values.
- Giving pediatric dosing of tocilizumab, with patients weighing less than 30 kg receiving 12 mg/kg, and those weighing 30 kg or greater receiving 8 mg/kg.
- Considering participation with a prospective collaboration with intensive-care registries that could allow accurate data entry of cell-therapy variables into the Center for International Blood and Marrow Transplant Research registry by cell-therapy programs.
The Food and Drug Administration approved the first two CAR T-cell therapies in the United States in 2017: Novartis’ tisagenlecleucel (Kymriah) for children and young adults with B-cell precursor acute lymphoblastic leukemia and later for adults with large B-cell lymphoma; and axicabtagene ciloleucel (Yescarta), sold by Gilead, for adults with large B-cell lymphoma. The therapies involve reengineering a patient’s T cells such that they recognize the threat of cancer, and then introducing them back into the body. The European Medicines Agency’s Committee for Medicinal Products for Human Use in June recommended granting marketing authorization to these drugs.
In the new pediatric guidelines, Dr. Mahadeo and his colleagues noted the use of CAR T-cell therapies for treatment of solid tumors and other malignancies in children already “is being explored.” “Moreover, consideration of earlier or upfront use of CAR T-cell therapy might spare patients the acute and long-term toxicities associated with traditional chemotherapy and/or radiation regimens,” they wrote.
There’s been great interest in learning how to most safely use the CAR T cell therapies, said Helen Heslop, MD, of Baylor College of Medicine.
She pointed to a 2014 publication in the journal Blood from Daniel W. Lee and his colleagues as an earlier example of this research. By now, cancer centers will have worked out their own procedures for pediatric use of CAR T therapies, hewing to standards set by the Foundation for the Accreditation of Cellular Therapy (FACT), Dr. Heslop said.
Dr. Heslop also stressed the role of the FDA in requiring risk evaluation and management strategy programs for these drugs. All of this, including the new guidelines from Dr. Mahadeo and his colleagues, is part of a growing body of research into safe use of CAR T therapies, Dr. Heslop said.
“It’s an active area of research,” she said. “Most centers will look at all of it and then develop what works best in their own individual center for providing the best care for the patients.”
The newly published guidelines could prove an “important contribution” to managing the risk of CAR T therapies, Phyllis I. Warkentin, MD, chief medical officer for FACT, said in an interview, while stressing that they were not more or less important than other similar efforts. Physicians learning how to use the CAR T therapies may welcome new input, as most of what’s been published has been about adults, she said.
“You don’t have the luxury of a lot of time to be learning on the job, so to speak,” with CAR T therapies, she said. “Many of the toxicities are fairly severe and fairly sudden.”
Dr. Heslop has been on advisory board for Gilead and Novartis. Dr. Warkentin and Dr. Mahadeo each reported having no financial disclosures. Other authors of the guidelines paper reported a patent with applications in the field of gene-modified T cell therapy for cancer, as well as financial ties to Cellectis, NexImmune, Torque Pharma, Kite Pharma (a Gilead company), Poseida Therapeutics, Celgene, Novartis, and Unum Therapeutics.
SOURCE: Mahadeo KM et al. Nat Rev Clin Oncol. 2018 Aug 6. doi: 10.1038/s41571-018-0075-2.
emphasize the need for a flexible approach to detect early signs of serious complications for younger patients treated with this emerging class of medicines.
Researchers at the University of Texas MD Anderson Cancer Center, Houston, and the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) developed the guidelines, which were published in Nature Reviews Clinical Oncology. The recommendations build on the guidelines for more general use of these medicines from MD Anderson’s CARTOX Program, which Nature Reviews Clinical Oncology published in 2017.
Among the chief concerns with this new class of medicines are cytokine-release syndrome (CRS) and CAR T cell-related encephalopathy syndrome (CRES), according to Kris Michael Mahadeo, MD MPH, of the MD Anderson Cancer Center and his coauthors of the new paper.
Some of the tools used for older patients in screening for complications with CAR T drugs don’t work as well with younger ones, Dr. Mahadeo said in an interview. For instance, at MD Anderson, a handwriting sample is used to monitor patients for CAR T cell-related encephalopathy syndrome, which has symptoms of confusion and delirium. Patients provide a baseline handwriting sample of a single sentence that’s scanned into the medical record, and then they are asked to write this again during their time in the hospital, he said. But this tool may not work for children too young to write well.
The new guidelines suggest using the Cornell Assessment of Pediatric Delirium (CAPD) or to evaluate a child’s mental state, asking questions about eye contact, and level of awareness and mood, Dr. Mahadeo said. An alternative for patients aged 12 years and older with greater cognitive ability is the CARTOX-10 grading system.
“The nurses who spent most of the day with these patients will observe them over their shift and kind of get an idea of what was normal and answer a series of questions” through the CAPD tool, which is already used in ICUs, Dr. Mahadeo said. “It takes into consideration both the nurses’ perception and the parents, or whoever is at the bedside with the child. So that if they have a concern, it gives them a point that actually escalates things upward.”
The newly published recommendations also remind physicians and others caring for young patients to pay attention to these reports.
“Parent and/or caregiver concerns should be addressed because early signs or symptoms of CRS can be subtle and best recognized by those who know the child best,” Dr. Mahadeo and his colleagues wrote in a summary of key recommendations in the paper.
The recommendations also noted a need for close monitoring for complications such as hypotension, hypocalcemia, and catheter-related pain in young patients who require a leukapheresis catheter for cell collection. Infant and younger children “might not verbalize these symptoms,” according to the researchers.
Other recommendations include:
- Obtaining the child’s assent when appropriate, with psychological services often aiding in this goal. Dr. Mahadeo and his colleagues recommend considering “age-appropriate advance directives.”
- Maintaining high vigilance for sinus tachycardia as an early sign of CRS, using age-specific normal range or baseline values.
- Giving pediatric dosing of tocilizumab, with patients weighing less than 30 kg receiving 12 mg/kg, and those weighing 30 kg or greater receiving 8 mg/kg.
- Considering participation with a prospective collaboration with intensive-care registries that could allow accurate data entry of cell-therapy variables into the Center for International Blood and Marrow Transplant Research registry by cell-therapy programs.
The Food and Drug Administration approved the first two CAR T-cell therapies in the United States in 2017: Novartis’ tisagenlecleucel (Kymriah) for children and young adults with B-cell precursor acute lymphoblastic leukemia and later for adults with large B-cell lymphoma; and axicabtagene ciloleucel (Yescarta), sold by Gilead, for adults with large B-cell lymphoma. The therapies involve reengineering a patient’s T cells such that they recognize the threat of cancer, and then introducing them back into the body. The European Medicines Agency’s Committee for Medicinal Products for Human Use in June recommended granting marketing authorization to these drugs.
In the new pediatric guidelines, Dr. Mahadeo and his colleagues noted the use of CAR T-cell therapies for treatment of solid tumors and other malignancies in children already “is being explored.” “Moreover, consideration of earlier or upfront use of CAR T-cell therapy might spare patients the acute and long-term toxicities associated with traditional chemotherapy and/or radiation regimens,” they wrote.
There’s been great interest in learning how to most safely use the CAR T cell therapies, said Helen Heslop, MD, of Baylor College of Medicine.
She pointed to a 2014 publication in the journal Blood from Daniel W. Lee and his colleagues as an earlier example of this research. By now, cancer centers will have worked out their own procedures for pediatric use of CAR T therapies, hewing to standards set by the Foundation for the Accreditation of Cellular Therapy (FACT), Dr. Heslop said.
Dr. Heslop also stressed the role of the FDA in requiring risk evaluation and management strategy programs for these drugs. All of this, including the new guidelines from Dr. Mahadeo and his colleagues, is part of a growing body of research into safe use of CAR T therapies, Dr. Heslop said.
“It’s an active area of research,” she said. “Most centers will look at all of it and then develop what works best in their own individual center for providing the best care for the patients.”
The newly published guidelines could prove an “important contribution” to managing the risk of CAR T therapies, Phyllis I. Warkentin, MD, chief medical officer for FACT, said in an interview, while stressing that they were not more or less important than other similar efforts. Physicians learning how to use the CAR T therapies may welcome new input, as most of what’s been published has been about adults, she said.
“You don’t have the luxury of a lot of time to be learning on the job, so to speak,” with CAR T therapies, she said. “Many of the toxicities are fairly severe and fairly sudden.”
Dr. Heslop has been on advisory board for Gilead and Novartis. Dr. Warkentin and Dr. Mahadeo each reported having no financial disclosures. Other authors of the guidelines paper reported a patent with applications in the field of gene-modified T cell therapy for cancer, as well as financial ties to Cellectis, NexImmune, Torque Pharma, Kite Pharma (a Gilead company), Poseida Therapeutics, Celgene, Novartis, and Unum Therapeutics.
SOURCE: Mahadeo KM et al. Nat Rev Clin Oncol. 2018 Aug 6. doi: 10.1038/s41571-018-0075-2.
emphasize the need for a flexible approach to detect early signs of serious complications for younger patients treated with this emerging class of medicines.
Researchers at the University of Texas MD Anderson Cancer Center, Houston, and the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) developed the guidelines, which were published in Nature Reviews Clinical Oncology. The recommendations build on the guidelines for more general use of these medicines from MD Anderson’s CARTOX Program, which Nature Reviews Clinical Oncology published in 2017.
Among the chief concerns with this new class of medicines are cytokine-release syndrome (CRS) and CAR T cell-related encephalopathy syndrome (CRES), according to Kris Michael Mahadeo, MD MPH, of the MD Anderson Cancer Center and his coauthors of the new paper.
Some of the tools used for older patients in screening for complications with CAR T drugs don’t work as well with younger ones, Dr. Mahadeo said in an interview. For instance, at MD Anderson, a handwriting sample is used to monitor patients for CAR T cell-related encephalopathy syndrome, which has symptoms of confusion and delirium. Patients provide a baseline handwriting sample of a single sentence that’s scanned into the medical record, and then they are asked to write this again during their time in the hospital, he said. But this tool may not work for children too young to write well.
The new guidelines suggest using the Cornell Assessment of Pediatric Delirium (CAPD) or to evaluate a child’s mental state, asking questions about eye contact, and level of awareness and mood, Dr. Mahadeo said. An alternative for patients aged 12 years and older with greater cognitive ability is the CARTOX-10 grading system.
“The nurses who spent most of the day with these patients will observe them over their shift and kind of get an idea of what was normal and answer a series of questions” through the CAPD tool, which is already used in ICUs, Dr. Mahadeo said. “It takes into consideration both the nurses’ perception and the parents, or whoever is at the bedside with the child. So that if they have a concern, it gives them a point that actually escalates things upward.”
The newly published recommendations also remind physicians and others caring for young patients to pay attention to these reports.
“Parent and/or caregiver concerns should be addressed because early signs or symptoms of CRS can be subtle and best recognized by those who know the child best,” Dr. Mahadeo and his colleagues wrote in a summary of key recommendations in the paper.
The recommendations also noted a need for close monitoring for complications such as hypotension, hypocalcemia, and catheter-related pain in young patients who require a leukapheresis catheter for cell collection. Infant and younger children “might not verbalize these symptoms,” according to the researchers.
Other recommendations include:
- Obtaining the child’s assent when appropriate, with psychological services often aiding in this goal. Dr. Mahadeo and his colleagues recommend considering “age-appropriate advance directives.”
- Maintaining high vigilance for sinus tachycardia as an early sign of CRS, using age-specific normal range or baseline values.
- Giving pediatric dosing of tocilizumab, with patients weighing less than 30 kg receiving 12 mg/kg, and those weighing 30 kg or greater receiving 8 mg/kg.
- Considering participation with a prospective collaboration with intensive-care registries that could allow accurate data entry of cell-therapy variables into the Center for International Blood and Marrow Transplant Research registry by cell-therapy programs.
The Food and Drug Administration approved the first two CAR T-cell therapies in the United States in 2017: Novartis’ tisagenlecleucel (Kymriah) for children and young adults with B-cell precursor acute lymphoblastic leukemia and later for adults with large B-cell lymphoma; and axicabtagene ciloleucel (Yescarta), sold by Gilead, for adults with large B-cell lymphoma. The therapies involve reengineering a patient’s T cells such that they recognize the threat of cancer, and then introducing them back into the body. The European Medicines Agency’s Committee for Medicinal Products for Human Use in June recommended granting marketing authorization to these drugs.
In the new pediatric guidelines, Dr. Mahadeo and his colleagues noted the use of CAR T-cell therapies for treatment of solid tumors and other malignancies in children already “is being explored.” “Moreover, consideration of earlier or upfront use of CAR T-cell therapy might spare patients the acute and long-term toxicities associated with traditional chemotherapy and/or radiation regimens,” they wrote.
There’s been great interest in learning how to most safely use the CAR T cell therapies, said Helen Heslop, MD, of Baylor College of Medicine.
She pointed to a 2014 publication in the journal Blood from Daniel W. Lee and his colleagues as an earlier example of this research. By now, cancer centers will have worked out their own procedures for pediatric use of CAR T therapies, hewing to standards set by the Foundation for the Accreditation of Cellular Therapy (FACT), Dr. Heslop said.
Dr. Heslop also stressed the role of the FDA in requiring risk evaluation and management strategy programs for these drugs. All of this, including the new guidelines from Dr. Mahadeo and his colleagues, is part of a growing body of research into safe use of CAR T therapies, Dr. Heslop said.
“It’s an active area of research,” she said. “Most centers will look at all of it and then develop what works best in their own individual center for providing the best care for the patients.”
The newly published guidelines could prove an “important contribution” to managing the risk of CAR T therapies, Phyllis I. Warkentin, MD, chief medical officer for FACT, said in an interview, while stressing that they were not more or less important than other similar efforts. Physicians learning how to use the CAR T therapies may welcome new input, as most of what’s been published has been about adults, she said.
“You don’t have the luxury of a lot of time to be learning on the job, so to speak,” with CAR T therapies, she said. “Many of the toxicities are fairly severe and fairly sudden.”
Dr. Heslop has been on advisory board for Gilead and Novartis. Dr. Warkentin and Dr. Mahadeo each reported having no financial disclosures. Other authors of the guidelines paper reported a patent with applications in the field of gene-modified T cell therapy for cancer, as well as financial ties to Cellectis, NexImmune, Torque Pharma, Kite Pharma (a Gilead company), Poseida Therapeutics, Celgene, Novartis, and Unum Therapeutics.
SOURCE: Mahadeo KM et al. Nat Rev Clin Oncol. 2018 Aug 6. doi: 10.1038/s41571-018-0075-2.
FROM NATURE REVIEWS CLINICAL ONCOLOGY
Key clinical point: Multidisciplinary approach aids in managing CAR T-cell therapy’s severe potential toxicities in children.
Major finding: The guideline calls for pediatric dosing of tocilizumab, with patients weighing less than 30 kg receiving 12 mg/kg, and those weighing 30 kg or greater receiving 8 mg/kg.
Study details: Consensus guidelines on the care of children receiving CAR T-cell therapy from the Pediatric Acute Lung Injury and Sepsis Investigators and the MD Anderson Cancer Center CARTOX program.
Disclosures: Dr. Mahadeo reported having no financial disclosures. Other coauthors reported a patent with applications in the field of gene-modified T cell therapy for cancer, as well as financial ties to Cellectis, NexImmune, Torque Pharma, Kite Pharma (a Gilead company), Poseida Therapeutics, Celgene, Novartis, and Unum Therapeutics.
Source: Mahadeo KM et al. Nat Rev Clin Oncol. 2018 Aug 6. doi: 10.1038/s41571-018-0075-2.
Drug could be repurposed for T-ALL
Venetoclax might improve the treatment of certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to preclinical research published in Leukemia.
Researchers found that a ribosomal defect—the R98S mutation in ribosomal protein L10 (RPL10 R98S)—causes overexpression of BCL-2 in T-ALL.
The BCL-2 inhibitor venetoclax induced apoptosis of RPL10 R98S T-ALL cells and inhibited leukemia progression in mouse models of RPL10 R98S T-ALL.
The researchers therefore believe venetoclax could be used, in combination with other drugs, to treat T-ALL patients with RPL10 R98S.
“In the past couple of years, it has become clear that ribosome defects play a role in different types of cancer,” said study author Kim De Keersmaecker, PhD, of KU Leuven in Leuven, Belgium.
“In the case of a ribosome defect, the cells still produce proteins, but the balance between their quantities is slightly off, which leads to cancer.”
Dr De Keersmaecker and her colleagues noted that RPL10 R98S affects 8% of pediatric patients with T-ALL.
With this study, the researchers found that RPL10 R98S mutant cells were more resilient than wild-type (WT) cells. In overgrowth condition, Ba/F3 RPL10 R98S mutant cells “displayed a clear survival benefit” over RPL10 WT cells.
Likewise, RPL10 R98S Jurkat cells exhibited a survival benefit over WT Jurkat cells in overgrowth condition. And RPL10 R98S Jurkat cells were more resistant to treatment with doxorubicin.
Dr De Keersmaecker and her colleagues said the increased survival they observed in RPL10 R98S mutant cells is associated with enhanced BCL-2 expression. So the team decided to test a BCL-2 inhibitor in RPL10 R98S leukemic cells.
In vitro, venetoclax induced slightly more apoptosis in Jurkat RPL10 R98S cells than WT Jurkat cells. In vivo, venetoclax induced apoptosis in RPL10 R98S T-ALL cells but not WT T-ALL cells.
The researchers also found that venetoclax could re-sensitize RPL10 R98S cells to doxorubicin.
Finally, the team injected RPL10 WT and R98S samples from pediatric T-ALL patients into mice and treated the animals with DMSO or venetoclax (50 mg/kg) once a week.
Venetoclax had very little effect on the RPL10 WT mice. Percentages of human CD45 T-ALL cells in the peripheral blood were similar whether mice received DMSO or venetoclax.
However, in the RPL10 R98S mice, those that received DMSO experienced disease progression, while there were no signs of leukemia progression in the peripheral blood of mice that received venetoclax.
The splenomegaly observed in DMSO-treated mice was “almost completely suppressed” in mice that received venetoclax, according to the researchers.
The team also said they observed a 30% to 50% suppression of human CD45 leukemia cell engraftment in the bone marrow and the presence of 30% to 40% mouse CD45 cells in mice treated with venetoclax.
On the other hand, mice treated with DMSO had more than 95% human leukemia infiltration in the bone marrow and no mouse CD45-expressing cells.
Dr De Keersmaecker and her colleagues said these results suggest RPL10 R98S pediatric T-ALL is sensitive to BCL-2 targeted therapies such as venetoclax. However, venetoclax alone would not be sufficient to treat this type of T-ALL.
“Patients with leukemia often get a drug cocktail, while our study only tested the BCL-2 inhibitor,” Dr De Keersmaecker said. “That’s why our follow-up study will focus on a cocktail of this BCL-2 inhibitor and other drugs. For patients with the ribosome defect analyzed in our study, this avenue is definitely worth examining in greater detail.”
Venetoclax might improve the treatment of certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to preclinical research published in Leukemia.
Researchers found that a ribosomal defect—the R98S mutation in ribosomal protein L10 (RPL10 R98S)—causes overexpression of BCL-2 in T-ALL.
The BCL-2 inhibitor venetoclax induced apoptosis of RPL10 R98S T-ALL cells and inhibited leukemia progression in mouse models of RPL10 R98S T-ALL.
The researchers therefore believe venetoclax could be used, in combination with other drugs, to treat T-ALL patients with RPL10 R98S.
“In the past couple of years, it has become clear that ribosome defects play a role in different types of cancer,” said study author Kim De Keersmaecker, PhD, of KU Leuven in Leuven, Belgium.
“In the case of a ribosome defect, the cells still produce proteins, but the balance between their quantities is slightly off, which leads to cancer.”
Dr De Keersmaecker and her colleagues noted that RPL10 R98S affects 8% of pediatric patients with T-ALL.
With this study, the researchers found that RPL10 R98S mutant cells were more resilient than wild-type (WT) cells. In overgrowth condition, Ba/F3 RPL10 R98S mutant cells “displayed a clear survival benefit” over RPL10 WT cells.
Likewise, RPL10 R98S Jurkat cells exhibited a survival benefit over WT Jurkat cells in overgrowth condition. And RPL10 R98S Jurkat cells were more resistant to treatment with doxorubicin.
Dr De Keersmaecker and her colleagues said the increased survival they observed in RPL10 R98S mutant cells is associated with enhanced BCL-2 expression. So the team decided to test a BCL-2 inhibitor in RPL10 R98S leukemic cells.
In vitro, venetoclax induced slightly more apoptosis in Jurkat RPL10 R98S cells than WT Jurkat cells. In vivo, venetoclax induced apoptosis in RPL10 R98S T-ALL cells but not WT T-ALL cells.
The researchers also found that venetoclax could re-sensitize RPL10 R98S cells to doxorubicin.
Finally, the team injected RPL10 WT and R98S samples from pediatric T-ALL patients into mice and treated the animals with DMSO or venetoclax (50 mg/kg) once a week.
Venetoclax had very little effect on the RPL10 WT mice. Percentages of human CD45 T-ALL cells in the peripheral blood were similar whether mice received DMSO or venetoclax.
However, in the RPL10 R98S mice, those that received DMSO experienced disease progression, while there were no signs of leukemia progression in the peripheral blood of mice that received venetoclax.
The splenomegaly observed in DMSO-treated mice was “almost completely suppressed” in mice that received venetoclax, according to the researchers.
The team also said they observed a 30% to 50% suppression of human CD45 leukemia cell engraftment in the bone marrow and the presence of 30% to 40% mouse CD45 cells in mice treated with venetoclax.
On the other hand, mice treated with DMSO had more than 95% human leukemia infiltration in the bone marrow and no mouse CD45-expressing cells.
Dr De Keersmaecker and her colleagues said these results suggest RPL10 R98S pediatric T-ALL is sensitive to BCL-2 targeted therapies such as venetoclax. However, venetoclax alone would not be sufficient to treat this type of T-ALL.
“Patients with leukemia often get a drug cocktail, while our study only tested the BCL-2 inhibitor,” Dr De Keersmaecker said. “That’s why our follow-up study will focus on a cocktail of this BCL-2 inhibitor and other drugs. For patients with the ribosome defect analyzed in our study, this avenue is definitely worth examining in greater detail.”
Venetoclax might improve the treatment of certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to preclinical research published in Leukemia.
Researchers found that a ribosomal defect—the R98S mutation in ribosomal protein L10 (RPL10 R98S)—causes overexpression of BCL-2 in T-ALL.
The BCL-2 inhibitor venetoclax induced apoptosis of RPL10 R98S T-ALL cells and inhibited leukemia progression in mouse models of RPL10 R98S T-ALL.
The researchers therefore believe venetoclax could be used, in combination with other drugs, to treat T-ALL patients with RPL10 R98S.
“In the past couple of years, it has become clear that ribosome defects play a role in different types of cancer,” said study author Kim De Keersmaecker, PhD, of KU Leuven in Leuven, Belgium.
“In the case of a ribosome defect, the cells still produce proteins, but the balance between their quantities is slightly off, which leads to cancer.”
Dr De Keersmaecker and her colleagues noted that RPL10 R98S affects 8% of pediatric patients with T-ALL.
With this study, the researchers found that RPL10 R98S mutant cells were more resilient than wild-type (WT) cells. In overgrowth condition, Ba/F3 RPL10 R98S mutant cells “displayed a clear survival benefit” over RPL10 WT cells.
Likewise, RPL10 R98S Jurkat cells exhibited a survival benefit over WT Jurkat cells in overgrowth condition. And RPL10 R98S Jurkat cells were more resistant to treatment with doxorubicin.
Dr De Keersmaecker and her colleagues said the increased survival they observed in RPL10 R98S mutant cells is associated with enhanced BCL-2 expression. So the team decided to test a BCL-2 inhibitor in RPL10 R98S leukemic cells.
In vitro, venetoclax induced slightly more apoptosis in Jurkat RPL10 R98S cells than WT Jurkat cells. In vivo, venetoclax induced apoptosis in RPL10 R98S T-ALL cells but not WT T-ALL cells.
The researchers also found that venetoclax could re-sensitize RPL10 R98S cells to doxorubicin.
Finally, the team injected RPL10 WT and R98S samples from pediatric T-ALL patients into mice and treated the animals with DMSO or venetoclax (50 mg/kg) once a week.
Venetoclax had very little effect on the RPL10 WT mice. Percentages of human CD45 T-ALL cells in the peripheral blood were similar whether mice received DMSO or venetoclax.
However, in the RPL10 R98S mice, those that received DMSO experienced disease progression, while there were no signs of leukemia progression in the peripheral blood of mice that received venetoclax.
The splenomegaly observed in DMSO-treated mice was “almost completely suppressed” in mice that received venetoclax, according to the researchers.
The team also said they observed a 30% to 50% suppression of human CD45 leukemia cell engraftment in the bone marrow and the presence of 30% to 40% mouse CD45 cells in mice treated with venetoclax.
On the other hand, mice treated with DMSO had more than 95% human leukemia infiltration in the bone marrow and no mouse CD45-expressing cells.
Dr De Keersmaecker and her colleagues said these results suggest RPL10 R98S pediatric T-ALL is sensitive to BCL-2 targeted therapies such as venetoclax. However, venetoclax alone would not be sufficient to treat this type of T-ALL.
“Patients with leukemia often get a drug cocktail, while our study only tested the BCL-2 inhibitor,” Dr De Keersmaecker said. “That’s why our follow-up study will focus on a cocktail of this BCL-2 inhibitor and other drugs. For patients with the ribosome defect analyzed in our study, this avenue is definitely worth examining in greater detail.”
Treatment guidelines for CAR T-cell therapy
Researchers have developed treatment guidelines for pediatric patients receiving chimeric antigen receptor (CAR) T-cell therapy.
The guidelines include recommendations for patient selection and consent, treatment details, and advice on managing cytokine release syndrome (CRS) and other adverse events associated with CAR T-cell therapy.
The guidelines were published in Nature Reviews Clinical Oncology.
“CAR T-cell therapy has been associated with remarkable response rates for children and young adults with ALL [acute lymphoblastic leukemia], yet this innovative form of cellular immunotherapy has resulted in unique and severe toxicities which can lead to rapid cardiorespiratory and/or neurological deterioration,” said guidelines author Kris Mahadeo, MD, of The University of Texas MD Anderson Cancer Center in Houston.
“This novel therapy requires the medical vigilance of a diverse multi-disciplinary team and associated clinical infrastructure to ensure optimal patient outcomes.”
Pediatric patient selection and consent
The guidelines state that providers of CAR T-cell therapies should adhere to product information labels and guidance from risk evaluation and mitigation strategy programs (level of evidence: IV, grade: D).
In addition, patient selection should be based on the indications approved by the US Food and Drug Administration and criteria used in pivotal studies. However, this can change as new information becomes available (level of evidence: IV, grade: D).
Informed consent should include descriptions of the risks and benefits associated with leukapheresis, lymphodepletion, CRS, CAR T-cell-related encephalopathy syndrome (CRES), bridging chemotherapy, intensive care support, and anti-IL-6 therapy (level of evidence: IIA, grade: B).
Providers should obtain child assent when appropriate and may benefit from incorporating child life and psychological services in assent discussions (level of evidence: IV, grade: D).
Treatment specifics
The guidelines recommend cyclophosphamide–fludarabine regimens for lymphodepletion, although exceptions can be considered in cases of hemorrhagic cystitis and/or resistance to a prior cyclophosphamide-based regimen (level of evidence: IIA, grade: B).
Providers should consider inpatient admission for a minimum of 3 to 7 days after receipt of tisagenlecleucel. This was based on the experience in pediatric and young adult patients with CD19+ relapsed and/or refractory B-cell acute lymphoblastic leukemia (level of evidence: IIA, grade: B).
Patients should be closely monitored for hypotension, hypocalcemia, and catheter-related pain during leukapheresis (level of evidence: IIA, grade: B).
For patients receiving tocilizumab, those weighing <30 kg should receive 12 mg/kg, and those weighing ≥30 kg should receive 8 mg/kg (level of evidence: IIA, grade: B).
Adverse events
The guidelines say parent and/or caregiver concerns should be addressed as these individuals may be best equipped to recognize early signs or symptoms of CRS (level of evidence: III, grade: C).
When CAR T-cell therapy is administered in an outpatient setting, there should be a low threshold for patient admission upon the development of signs or symptoms suggestive of CRS and/or CRES (level of evidence: IIA, grade: B).
CRS grading should be performed at least once every 12 hours (level of evidence: IIA, grade: B). Detailed information on grading is provided in the guidelines.
Providers should suspect CRS if any of the following signs/symptoms are present within the first 2 weeks of CAR T-cell infusion:
- Fever ≥38 °C
- Hypotension
- Hypoxia with an arterial oxygen saturation of <90% on room air
- Evidence of organ toxicity as determined by the most recent CTCAE grading system and considerations detailed in the guidelines (level of evidence: IIA, grade: C).
The guidelines also recommend “high vigilance” for sinus tachycardia as an early sign of CRS (level of evidence: IIA, grade: B) as well as application of the PALICC (Pediatric Acute Lung Injury Consensus Conference) at-risk P-ARDS (pediatric acute respiratory distress syndrome) criteria for the CRS grading of hypoxia (level of evidence: IIA, grade: B).
Hemophagocytic lymphohistiocytosis and/or macrophage-activation syndrome can be treated with anti-IL-6 therapy and corticosteroids. However, refractory cases may require systemic and/or intrathecal therapy or use of the IL-1 receptor antagonist anakinra (level of evidence: IIA, grade: C).
The guidelines recommend that delirium screening be performed at least twice per 24-hour period among admitted patients and at least daily among outpatients during the high-risk periods for CRES (level of evidence: IIA, grade: C). Delirium screening should be performed with the CAPD (Cornell Assessment of Pediatric Delirium) tool or CARTOX-10 (CAR T-Cell Therapy-Associated Toxicity 10-point assessment scale) for patients age 12 and older who have sufficient cognitive abilities.
Acute kidney injury in children can be graded according to the CTCAE (Common Terminology Criteria for Adverse Events) using pRIFLE (Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease) and KDIGO (Kidney Disease: Improving Global Outcomes) definitions of oliguria (level of evidence: IIA, grade: B).
Other considerations
The guidelines “strongly encourage” consideration of quality-adjusted life-years gained for pediatric patients who might achieve long-term remission from CAR T-cell therapy and encourage efforts to reduce the cost of care (level of evidence: IV, grade: D).
The guidelines also recommend that CAR T-cell programs seek FACT IEC (Foundation for the Accreditation of Cellular Therapy for Immune Effector Cells) accreditation to ensure adherence to quality standards (level of evidence: IV, grade: D).
Finally, the guidelines suggest the possibility of a prospective collaboration with intensive-care registries, which could allow accurate data entry of cell therapy variables into the CIBMTR registry with concurrent entry of intensive-care variables into an appropriate registry by pediatric critical care teams (level of evidence: IV, grade: D).
Researchers have developed treatment guidelines for pediatric patients receiving chimeric antigen receptor (CAR) T-cell therapy.
The guidelines include recommendations for patient selection and consent, treatment details, and advice on managing cytokine release syndrome (CRS) and other adverse events associated with CAR T-cell therapy.
The guidelines were published in Nature Reviews Clinical Oncology.
“CAR T-cell therapy has been associated with remarkable response rates for children and young adults with ALL [acute lymphoblastic leukemia], yet this innovative form of cellular immunotherapy has resulted in unique and severe toxicities which can lead to rapid cardiorespiratory and/or neurological deterioration,” said guidelines author Kris Mahadeo, MD, of The University of Texas MD Anderson Cancer Center in Houston.
“This novel therapy requires the medical vigilance of a diverse multi-disciplinary team and associated clinical infrastructure to ensure optimal patient outcomes.”
Pediatric patient selection and consent
The guidelines state that providers of CAR T-cell therapies should adhere to product information labels and guidance from risk evaluation and mitigation strategy programs (level of evidence: IV, grade: D).
In addition, patient selection should be based on the indications approved by the US Food and Drug Administration and criteria used in pivotal studies. However, this can change as new information becomes available (level of evidence: IV, grade: D).
Informed consent should include descriptions of the risks and benefits associated with leukapheresis, lymphodepletion, CRS, CAR T-cell-related encephalopathy syndrome (CRES), bridging chemotherapy, intensive care support, and anti-IL-6 therapy (level of evidence: IIA, grade: B).
Providers should obtain child assent when appropriate and may benefit from incorporating child life and psychological services in assent discussions (level of evidence: IV, grade: D).
Treatment specifics
The guidelines recommend cyclophosphamide–fludarabine regimens for lymphodepletion, although exceptions can be considered in cases of hemorrhagic cystitis and/or resistance to a prior cyclophosphamide-based regimen (level of evidence: IIA, grade: B).
Providers should consider inpatient admission for a minimum of 3 to 7 days after receipt of tisagenlecleucel. This was based on the experience in pediatric and young adult patients with CD19+ relapsed and/or refractory B-cell acute lymphoblastic leukemia (level of evidence: IIA, grade: B).
Patients should be closely monitored for hypotension, hypocalcemia, and catheter-related pain during leukapheresis (level of evidence: IIA, grade: B).
For patients receiving tocilizumab, those weighing <30 kg should receive 12 mg/kg, and those weighing ≥30 kg should receive 8 mg/kg (level of evidence: IIA, grade: B).
Adverse events
The guidelines say parent and/or caregiver concerns should be addressed as these individuals may be best equipped to recognize early signs or symptoms of CRS (level of evidence: III, grade: C).
When CAR T-cell therapy is administered in an outpatient setting, there should be a low threshold for patient admission upon the development of signs or symptoms suggestive of CRS and/or CRES (level of evidence: IIA, grade: B).
CRS grading should be performed at least once every 12 hours (level of evidence: IIA, grade: B). Detailed information on grading is provided in the guidelines.
Providers should suspect CRS if any of the following signs/symptoms are present within the first 2 weeks of CAR T-cell infusion:
- Fever ≥38 °C
- Hypotension
- Hypoxia with an arterial oxygen saturation of <90% on room air
- Evidence of organ toxicity as determined by the most recent CTCAE grading system and considerations detailed in the guidelines (level of evidence: IIA, grade: C).
The guidelines also recommend “high vigilance” for sinus tachycardia as an early sign of CRS (level of evidence: IIA, grade: B) as well as application of the PALICC (Pediatric Acute Lung Injury Consensus Conference) at-risk P-ARDS (pediatric acute respiratory distress syndrome) criteria for the CRS grading of hypoxia (level of evidence: IIA, grade: B).
Hemophagocytic lymphohistiocytosis and/or macrophage-activation syndrome can be treated with anti-IL-6 therapy and corticosteroids. However, refractory cases may require systemic and/or intrathecal therapy or use of the IL-1 receptor antagonist anakinra (level of evidence: IIA, grade: C).
The guidelines recommend that delirium screening be performed at least twice per 24-hour period among admitted patients and at least daily among outpatients during the high-risk periods for CRES (level of evidence: IIA, grade: C). Delirium screening should be performed with the CAPD (Cornell Assessment of Pediatric Delirium) tool or CARTOX-10 (CAR T-Cell Therapy-Associated Toxicity 10-point assessment scale) for patients age 12 and older who have sufficient cognitive abilities.
Acute kidney injury in children can be graded according to the CTCAE (Common Terminology Criteria for Adverse Events) using pRIFLE (Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease) and KDIGO (Kidney Disease: Improving Global Outcomes) definitions of oliguria (level of evidence: IIA, grade: B).
Other considerations
The guidelines “strongly encourage” consideration of quality-adjusted life-years gained for pediatric patients who might achieve long-term remission from CAR T-cell therapy and encourage efforts to reduce the cost of care (level of evidence: IV, grade: D).
The guidelines also recommend that CAR T-cell programs seek FACT IEC (Foundation for the Accreditation of Cellular Therapy for Immune Effector Cells) accreditation to ensure adherence to quality standards (level of evidence: IV, grade: D).
Finally, the guidelines suggest the possibility of a prospective collaboration with intensive-care registries, which could allow accurate data entry of cell therapy variables into the CIBMTR registry with concurrent entry of intensive-care variables into an appropriate registry by pediatric critical care teams (level of evidence: IV, grade: D).
Researchers have developed treatment guidelines for pediatric patients receiving chimeric antigen receptor (CAR) T-cell therapy.
The guidelines include recommendations for patient selection and consent, treatment details, and advice on managing cytokine release syndrome (CRS) and other adverse events associated with CAR T-cell therapy.
The guidelines were published in Nature Reviews Clinical Oncology.
“CAR T-cell therapy has been associated with remarkable response rates for children and young adults with ALL [acute lymphoblastic leukemia], yet this innovative form of cellular immunotherapy has resulted in unique and severe toxicities which can lead to rapid cardiorespiratory and/or neurological deterioration,” said guidelines author Kris Mahadeo, MD, of The University of Texas MD Anderson Cancer Center in Houston.
“This novel therapy requires the medical vigilance of a diverse multi-disciplinary team and associated clinical infrastructure to ensure optimal patient outcomes.”
Pediatric patient selection and consent
The guidelines state that providers of CAR T-cell therapies should adhere to product information labels and guidance from risk evaluation and mitigation strategy programs (level of evidence: IV, grade: D).
In addition, patient selection should be based on the indications approved by the US Food and Drug Administration and criteria used in pivotal studies. However, this can change as new information becomes available (level of evidence: IV, grade: D).
Informed consent should include descriptions of the risks and benefits associated with leukapheresis, lymphodepletion, CRS, CAR T-cell-related encephalopathy syndrome (CRES), bridging chemotherapy, intensive care support, and anti-IL-6 therapy (level of evidence: IIA, grade: B).
Providers should obtain child assent when appropriate and may benefit from incorporating child life and psychological services in assent discussions (level of evidence: IV, grade: D).
Treatment specifics
The guidelines recommend cyclophosphamide–fludarabine regimens for lymphodepletion, although exceptions can be considered in cases of hemorrhagic cystitis and/or resistance to a prior cyclophosphamide-based regimen (level of evidence: IIA, grade: B).
Providers should consider inpatient admission for a minimum of 3 to 7 days after receipt of tisagenlecleucel. This was based on the experience in pediatric and young adult patients with CD19+ relapsed and/or refractory B-cell acute lymphoblastic leukemia (level of evidence: IIA, grade: B).
Patients should be closely monitored for hypotension, hypocalcemia, and catheter-related pain during leukapheresis (level of evidence: IIA, grade: B).
For patients receiving tocilizumab, those weighing <30 kg should receive 12 mg/kg, and those weighing ≥30 kg should receive 8 mg/kg (level of evidence: IIA, grade: B).
Adverse events
The guidelines say parent and/or caregiver concerns should be addressed as these individuals may be best equipped to recognize early signs or symptoms of CRS (level of evidence: III, grade: C).
When CAR T-cell therapy is administered in an outpatient setting, there should be a low threshold for patient admission upon the development of signs or symptoms suggestive of CRS and/or CRES (level of evidence: IIA, grade: B).
CRS grading should be performed at least once every 12 hours (level of evidence: IIA, grade: B). Detailed information on grading is provided in the guidelines.
Providers should suspect CRS if any of the following signs/symptoms are present within the first 2 weeks of CAR T-cell infusion:
- Fever ≥38 °C
- Hypotension
- Hypoxia with an arterial oxygen saturation of <90% on room air
- Evidence of organ toxicity as determined by the most recent CTCAE grading system and considerations detailed in the guidelines (level of evidence: IIA, grade: C).
The guidelines also recommend “high vigilance” for sinus tachycardia as an early sign of CRS (level of evidence: IIA, grade: B) as well as application of the PALICC (Pediatric Acute Lung Injury Consensus Conference) at-risk P-ARDS (pediatric acute respiratory distress syndrome) criteria for the CRS grading of hypoxia (level of evidence: IIA, grade: B).
Hemophagocytic lymphohistiocytosis and/or macrophage-activation syndrome can be treated with anti-IL-6 therapy and corticosteroids. However, refractory cases may require systemic and/or intrathecal therapy or use of the IL-1 receptor antagonist anakinra (level of evidence: IIA, grade: C).
The guidelines recommend that delirium screening be performed at least twice per 24-hour period among admitted patients and at least daily among outpatients during the high-risk periods for CRES (level of evidence: IIA, grade: C). Delirium screening should be performed with the CAPD (Cornell Assessment of Pediatric Delirium) tool or CARTOX-10 (CAR T-Cell Therapy-Associated Toxicity 10-point assessment scale) for patients age 12 and older who have sufficient cognitive abilities.
Acute kidney injury in children can be graded according to the CTCAE (Common Terminology Criteria for Adverse Events) using pRIFLE (Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease) and KDIGO (Kidney Disease: Improving Global Outcomes) definitions of oliguria (level of evidence: IIA, grade: B).
Other considerations
The guidelines “strongly encourage” consideration of quality-adjusted life-years gained for pediatric patients who might achieve long-term remission from CAR T-cell therapy and encourage efforts to reduce the cost of care (level of evidence: IV, grade: D).
The guidelines also recommend that CAR T-cell programs seek FACT IEC (Foundation for the Accreditation of Cellular Therapy for Immune Effector Cells) accreditation to ensure adherence to quality standards (level of evidence: IV, grade: D).
Finally, the guidelines suggest the possibility of a prospective collaboration with intensive-care registries, which could allow accurate data entry of cell therapy variables into the CIBMTR registry with concurrent entry of intensive-care variables into an appropriate registry by pediatric critical care teams (level of evidence: IV, grade: D).
Adult CCSs report financial hardships
Health-related financial hardship is common among adult survivors of childhood cancer, according to a study published in the Journal of the National Cancer Institute.
Researchers analyzed more than 2800 long-term childhood cancer survivors (CCSs) and found that 65% had financial challenges related to their cancer diagnosis.
“These findings suggest primary care doctors and oncologists should routinely screen childhood cancer survivors for possible financial hardship,” said I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Specifically, Dr Huang recommends that healthcare providers routinely ask CCSs if they are unable to purchase medications, ever skip appointments for economic reasons, or worry about how to pay their medical bills.
For this study, Dr Huang and his colleagues analyzed data from 2811 CCSs. The subjects had a mean age of 31.8 (range, 18 to 65) and were a mean of 23.6 years from cancer diagnosis. Most (57.8%) had been diagnosed with hematologic malignancies, 32.0% with solid tumors, and 10.1% with central nervous system malignancies.
All subjects had been treated at St. Jude and enrolled in the St. Jude LIFE study. Participants return to St. Jude periodically for several days of clinical and functional assessments. Data for this study were collected during the CCSs’ first St. Jude LIFE evaluations.
Assessing hardship
The researchers measured 3 types of financial hardship—material, psychological, and coping/behavioral.
About 1 in 5 CCSs (22.4%) reported material financial hardship. In other words, their cancer had an impact on their financial situation.
More than half of CCSs (51.1%) reported psychological hardship—concern about their ability to pay for medical expenses.
And 33% of CCSs reported coping/behavioral hardship—an inability to see a doctor or go to the hospital due to finances.
Roughly 65% of CCSs reported at least 1 type of financial hardship.
All 3 types of hardship were significantly associated with somatization (all P<0.001), anxiety (all P<0.001), depression (all P<0.001), suicidal thoughts (all P<0.05), and difficulty in retirement planning (all P<0.001).
Furthermore, CCSs who reported financial hardship had significantly lower health-related quality of life (P<0.001 for all 3 domains), sensation abnormality (all P<0.001), pulmonary symptoms (all P<0.05), and cardiac symptoms (all P<0.05).
Predicting hardship
Intensive cancer treatment, chronic health conditions, second cancers, age at the time of study evaluation, education level, and annual household income were all significantly associated with a greater risk of financial hardship.
CCSs age 40 and older had an increased risk of psychological and coping/behavioral hardship (P<0.001 for both domains).
CCSs with an annual household income of less than $40,000 had an increased risk of material, psychological, and coping/behavioral hardship, compared to CCSs with an income of $80,000 or more (P<0.001 for all domains).
CCSs who did not obtain a high school diploma had an increased risk of material (P<0.001), psychological (P<0.01), and coping/behavioral hardship (P<0.001) compared to college graduates.
CCSs who received cancer treatments associated with a high-risk disease burden (vs low-risk) had an increased risk of material (P=0.01) and psychological (P=0.004) hardship.
Health conditions associated with material financial hardship included grade 2-4 myocardial infarction (P<0.001), peripheral neuropathy (P<0.001), subsequent neoplasm (P<0.001), seizure (P=0.007), reproductive disorders (P=0.01), stroke (P=0.02), amputation (P=0.02), upper gastrointestinal disease (P=0.04), and hearing loss (P=0.05).
Grade 2-4 myocardial infarction and reproductive disorders were significantly associated with psychological financial hardship (P=0.02 for both).
“Severe late effects that emerge early in life and disrupt education and training opportunities are a double hit for survivors,” Dr Huang said. “These health problems decrease the survivors’ earning mobility and financial security later in life. The phenomenon leaves them at risk for poor health and psychological outcomes compared to healthier survivors.”
Health-related financial hardship is common among adult survivors of childhood cancer, according to a study published in the Journal of the National Cancer Institute.
Researchers analyzed more than 2800 long-term childhood cancer survivors (CCSs) and found that 65% had financial challenges related to their cancer diagnosis.
“These findings suggest primary care doctors and oncologists should routinely screen childhood cancer survivors for possible financial hardship,” said I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Specifically, Dr Huang recommends that healthcare providers routinely ask CCSs if they are unable to purchase medications, ever skip appointments for economic reasons, or worry about how to pay their medical bills.
For this study, Dr Huang and his colleagues analyzed data from 2811 CCSs. The subjects had a mean age of 31.8 (range, 18 to 65) and were a mean of 23.6 years from cancer diagnosis. Most (57.8%) had been diagnosed with hematologic malignancies, 32.0% with solid tumors, and 10.1% with central nervous system malignancies.
All subjects had been treated at St. Jude and enrolled in the St. Jude LIFE study. Participants return to St. Jude periodically for several days of clinical and functional assessments. Data for this study were collected during the CCSs’ first St. Jude LIFE evaluations.
Assessing hardship
The researchers measured 3 types of financial hardship—material, psychological, and coping/behavioral.
About 1 in 5 CCSs (22.4%) reported material financial hardship. In other words, their cancer had an impact on their financial situation.
More than half of CCSs (51.1%) reported psychological hardship—concern about their ability to pay for medical expenses.
And 33% of CCSs reported coping/behavioral hardship—an inability to see a doctor or go to the hospital due to finances.
Roughly 65% of CCSs reported at least 1 type of financial hardship.
All 3 types of hardship were significantly associated with somatization (all P<0.001), anxiety (all P<0.001), depression (all P<0.001), suicidal thoughts (all P<0.05), and difficulty in retirement planning (all P<0.001).
Furthermore, CCSs who reported financial hardship had significantly lower health-related quality of life (P<0.001 for all 3 domains), sensation abnormality (all P<0.001), pulmonary symptoms (all P<0.05), and cardiac symptoms (all P<0.05).
Predicting hardship
Intensive cancer treatment, chronic health conditions, second cancers, age at the time of study evaluation, education level, and annual household income were all significantly associated with a greater risk of financial hardship.
CCSs age 40 and older had an increased risk of psychological and coping/behavioral hardship (P<0.001 for both domains).
CCSs with an annual household income of less than $40,000 had an increased risk of material, psychological, and coping/behavioral hardship, compared to CCSs with an income of $80,000 or more (P<0.001 for all domains).
CCSs who did not obtain a high school diploma had an increased risk of material (P<0.001), psychological (P<0.01), and coping/behavioral hardship (P<0.001) compared to college graduates.
CCSs who received cancer treatments associated with a high-risk disease burden (vs low-risk) had an increased risk of material (P=0.01) and psychological (P=0.004) hardship.
Health conditions associated with material financial hardship included grade 2-4 myocardial infarction (P<0.001), peripheral neuropathy (P<0.001), subsequent neoplasm (P<0.001), seizure (P=0.007), reproductive disorders (P=0.01), stroke (P=0.02), amputation (P=0.02), upper gastrointestinal disease (P=0.04), and hearing loss (P=0.05).
Grade 2-4 myocardial infarction and reproductive disorders were significantly associated with psychological financial hardship (P=0.02 for both).
“Severe late effects that emerge early in life and disrupt education and training opportunities are a double hit for survivors,” Dr Huang said. “These health problems decrease the survivors’ earning mobility and financial security later in life. The phenomenon leaves them at risk for poor health and psychological outcomes compared to healthier survivors.”
Health-related financial hardship is common among adult survivors of childhood cancer, according to a study published in the Journal of the National Cancer Institute.
Researchers analyzed more than 2800 long-term childhood cancer survivors (CCSs) and found that 65% had financial challenges related to their cancer diagnosis.
“These findings suggest primary care doctors and oncologists should routinely screen childhood cancer survivors for possible financial hardship,” said I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Specifically, Dr Huang recommends that healthcare providers routinely ask CCSs if they are unable to purchase medications, ever skip appointments for economic reasons, or worry about how to pay their medical bills.
For this study, Dr Huang and his colleagues analyzed data from 2811 CCSs. The subjects had a mean age of 31.8 (range, 18 to 65) and were a mean of 23.6 years from cancer diagnosis. Most (57.8%) had been diagnosed with hematologic malignancies, 32.0% with solid tumors, and 10.1% with central nervous system malignancies.
All subjects had been treated at St. Jude and enrolled in the St. Jude LIFE study. Participants return to St. Jude periodically for several days of clinical and functional assessments. Data for this study were collected during the CCSs’ first St. Jude LIFE evaluations.
Assessing hardship
The researchers measured 3 types of financial hardship—material, psychological, and coping/behavioral.
About 1 in 5 CCSs (22.4%) reported material financial hardship. In other words, their cancer had an impact on their financial situation.
More than half of CCSs (51.1%) reported psychological hardship—concern about their ability to pay for medical expenses.
And 33% of CCSs reported coping/behavioral hardship—an inability to see a doctor or go to the hospital due to finances.
Roughly 65% of CCSs reported at least 1 type of financial hardship.
All 3 types of hardship were significantly associated with somatization (all P<0.001), anxiety (all P<0.001), depression (all P<0.001), suicidal thoughts (all P<0.05), and difficulty in retirement planning (all P<0.001).
Furthermore, CCSs who reported financial hardship had significantly lower health-related quality of life (P<0.001 for all 3 domains), sensation abnormality (all P<0.001), pulmonary symptoms (all P<0.05), and cardiac symptoms (all P<0.05).
Predicting hardship
Intensive cancer treatment, chronic health conditions, second cancers, age at the time of study evaluation, education level, and annual household income were all significantly associated with a greater risk of financial hardship.
CCSs age 40 and older had an increased risk of psychological and coping/behavioral hardship (P<0.001 for both domains).
CCSs with an annual household income of less than $40,000 had an increased risk of material, psychological, and coping/behavioral hardship, compared to CCSs with an income of $80,000 or more (P<0.001 for all domains).
CCSs who did not obtain a high school diploma had an increased risk of material (P<0.001), psychological (P<0.01), and coping/behavioral hardship (P<0.001) compared to college graduates.
CCSs who received cancer treatments associated with a high-risk disease burden (vs low-risk) had an increased risk of material (P=0.01) and psychological (P=0.004) hardship.
Health conditions associated with material financial hardship included grade 2-4 myocardial infarction (P<0.001), peripheral neuropathy (P<0.001), subsequent neoplasm (P<0.001), seizure (P=0.007), reproductive disorders (P=0.01), stroke (P=0.02), amputation (P=0.02), upper gastrointestinal disease (P=0.04), and hearing loss (P=0.05).
Grade 2-4 myocardial infarction and reproductive disorders were significantly associated with psychological financial hardship (P=0.02 for both).
“Severe late effects that emerge early in life and disrupt education and training opportunities are a double hit for survivors,” Dr Huang said. “These health problems decrease the survivors’ earning mobility and financial security later in life. The phenomenon leaves them at risk for poor health and psychological outcomes compared to healthier survivors.”
CHMP announces 2 opinions on blinatumomab
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has released 2 new opinions regarding blinatumomab (Blincyto).
The CHMP recommended expanding the approved use of blinatumomab to include pediatric patients, but the committee also recommended against approving blinatumomab to treat patients with minimal residual disease (MRD).
Blinatumomab is already approved by the European Commission (EC) as monotherapy for adults with Philadelphia chromosome-negative (Ph-), CD19-positive, relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Now, the CHMP has recommended expanding this use to include blinatumomab as monotherapy for patients age 1 and older with Ph-, CD19-positive, relapsed/refractory BCP-ALL. These patients must have at least 2 prior therapies or have relapsed after allogeneic hematopoietic stem cell transplant.
This recommendation was supported by data from Study ‘205. Results from this phase 1/2 study were published in the Journal of Clinical Oncology in 2016.
The CHMP has also recommended against approving blinatumomab to treat BCP-ALL patients with MRD.
This decision was influenced by data from the BLAST study. Results from this phase 2 study were published in Blood earlier this year.
The CHMP noted that, although blinatumomab helped clear away residual cells in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.
Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.
Amgen, the company developing and marketing blinatumomab, can request a re-examination of the CHMP’s opinion within 15 days of receiving it.
The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of CHMP recommendations.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has released 2 new opinions regarding blinatumomab (Blincyto).
The CHMP recommended expanding the approved use of blinatumomab to include pediatric patients, but the committee also recommended against approving blinatumomab to treat patients with minimal residual disease (MRD).
Blinatumomab is already approved by the European Commission (EC) as monotherapy for adults with Philadelphia chromosome-negative (Ph-), CD19-positive, relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Now, the CHMP has recommended expanding this use to include blinatumomab as monotherapy for patients age 1 and older with Ph-, CD19-positive, relapsed/refractory BCP-ALL. These patients must have at least 2 prior therapies or have relapsed after allogeneic hematopoietic stem cell transplant.
This recommendation was supported by data from Study ‘205. Results from this phase 1/2 study were published in the Journal of Clinical Oncology in 2016.
The CHMP has also recommended against approving blinatumomab to treat BCP-ALL patients with MRD.
This decision was influenced by data from the BLAST study. Results from this phase 2 study were published in Blood earlier this year.
The CHMP noted that, although blinatumomab helped clear away residual cells in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.
Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.
Amgen, the company developing and marketing blinatumomab, can request a re-examination of the CHMP’s opinion within 15 days of receiving it.
The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of CHMP recommendations.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has released 2 new opinions regarding blinatumomab (Blincyto).
The CHMP recommended expanding the approved use of blinatumomab to include pediatric patients, but the committee also recommended against approving blinatumomab to treat patients with minimal residual disease (MRD).
Blinatumomab is already approved by the European Commission (EC) as monotherapy for adults with Philadelphia chromosome-negative (Ph-), CD19-positive, relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Now, the CHMP has recommended expanding this use to include blinatumomab as monotherapy for patients age 1 and older with Ph-, CD19-positive, relapsed/refractory BCP-ALL. These patients must have at least 2 prior therapies or have relapsed after allogeneic hematopoietic stem cell transplant.
This recommendation was supported by data from Study ‘205. Results from this phase 1/2 study were published in the Journal of Clinical Oncology in 2016.
The CHMP has also recommended against approving blinatumomab to treat BCP-ALL patients with MRD.
This decision was influenced by data from the BLAST study. Results from this phase 2 study were published in Blood earlier this year.
The CHMP noted that, although blinatumomab helped clear away residual cells in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.
Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.
Amgen, the company developing and marketing blinatumomab, can request a re-examination of the CHMP’s opinion within 15 days of receiving it.
The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of CHMP recommendations.
Global burden of hematologic malignancies
Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.
The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.
These increases were largely due to population growth and aging.
Results from the GDB study were published in JAMA Oncology.
The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.
One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).
The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.
| Cancer type | Cases, thousands | Deaths, thousands |
| All cancers | 17,228 | 8927 |
| Leukemias | 467 | 310 |
| Acute lymphoid leukemia | 76 | 51 |
| Chronic lymphoid leukemia | 105 | 35 |
| Acute myeloid leukemia | 103 | 85 |
| Chronic myeloid leukemia | 32 | 22 |
| Other leukemias | 150 | 117 |
| Hodgkin lymphoma | 73 | 29 |
| NHL | 461 | 240 |
| Multiple myeloma | 139 | 98 |
Leukemia
In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.
Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.
The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).
NHL
In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.
Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.
The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).
“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.
The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.
Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.
The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.
These increases were largely due to population growth and aging.
Results from the GDB study were published in JAMA Oncology.
The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.
One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).
The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.
| Cancer type | Cases, thousands | Deaths, thousands |
| All cancers | 17,228 | 8927 |
| Leukemias | 467 | 310 |
| Acute lymphoid leukemia | 76 | 51 |
| Chronic lymphoid leukemia | 105 | 35 |
| Acute myeloid leukemia | 103 | 85 |
| Chronic myeloid leukemia | 32 | 22 |
| Other leukemias | 150 | 117 |
| Hodgkin lymphoma | 73 | 29 |
| NHL | 461 | 240 |
| Multiple myeloma | 139 | 98 |
Leukemia
In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.
Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.
The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).
NHL
In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.
Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.
The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).
“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.
The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.
Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.
The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.
These increases were largely due to population growth and aging.
Results from the GDB study were published in JAMA Oncology.
The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.
One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).
The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.
| Cancer type | Cases, thousands | Deaths, thousands |
| All cancers | 17,228 | 8927 |
| Leukemias | 467 | 310 |
| Acute lymphoid leukemia | 76 | 51 |
| Chronic lymphoid leukemia | 105 | 35 |
| Acute myeloid leukemia | 103 | 85 |
| Chronic myeloid leukemia | 32 | 22 |
| Other leukemias | 150 | 117 |
| Hodgkin lymphoma | 73 | 29 |
| NHL | 461 | 240 |
| Multiple myeloma | 139 | 98 |
Leukemia
In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.
Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.
The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).
NHL
In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.
Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.
The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).
“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.
The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.