Lymphoma & Plasma Cell Disorders

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

With the help of gene expression signatures, a simulated treatment learning model identified which patients with multiple myeloma would benefit most from treatment with bortezomib or lenalidomide, researchers reported in Nature Communications.

The study included 910 participants across three phase 3 trials. In all, 20% would have a 100% greater-than-average progression-free survival (PFS) benefit from bortezomib, while 31% would have a 200% greater-than-average PFS benefit from lenalidomide, wrote Joske Ubels of University Center Utrecht, the Netherlands, and her colleagues.

The genetic heterogeneity of cancer and risk of treatment necessitate tools that “predict – at the moment of diagnosis – which patients will benefit most from a certain treatment,” the researchers wrote. While gene expression signatures can predict a favorable or adverse prognosis, they do not account for the effect of treatment on survival.

“The key idea of simulated treatment learning is that a patient’s treatment benefit can be estimated by comparing [his or her] survival to a set of genetically similar patients [who] received the comparator treatment,” they noted.

To do so, the researchers applied an algorithm called GESTURE to combined data from the TT2 (Total Therapy 2 for Multiple Myeloma), TT3, and HOVON-65/GMMG-HD4 trials. These trials compared bortezomib or lenalidomide with conventional therapies for multiple myeloma. The model identified 180 patients (20%) for whom bortezomib would produce a 100% greater PFS benefit than in the study population as a whole. Conversely, lenalidomide would produce a 200% greater PFS benefit in 31% of patients.

The simulated treatment learning model “can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment,” the researchers concluded. The method requires a large dataset but could be useful for trials that have missed their primary endpoint, such as the CheckMate-026 trial of nivolumab. The next step is to see if the model makes useful treatment predictions for other cancers. The code needed to train and validate the model is available at github.com/jubels/GESTURE.

The Van Herk Fellowship provided support. The lenalidomide dataset was created as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiative. Dr. Ubels and one coinvestigator are employees of SkylineDx; another coinvestigator served on its advisory board. The others reported having no relevant conflicts of interest.

SOURCE: Ubels J et al. Nat Commun. 2018 Jul 27. doi: 10.1038/s41467-018-05348-5.

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 pegfilgrastim biosimilar candidates—Udenyca and Pelgraz.

Both products have been deemed highly similar to the reference product, Neulasta, a growth-colony-stimulating factor intended to reduce the duration of neutropenia and the incidence of febrile neutropenia due to chemotherapy.

The CHMP’s recommendations for Pelgraz and Udenyca will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Udenyca and Pelgraz will be available as 6 mg solutions for injection.

The full indication for both products will be to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies, except chronic myeloid leukemia and myelodysplastic syndromes.

The CHMP said data have shown that Pelgraz and Udenyca both have comparable quality, safety, and efficacy to Neulasta.

Pelgraz’s marketing authorization application is supported by data from a phase 1 pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy volunteers and a phase 3 study of breast cancer patients receiving docetaxel, doxorubicin, and cyclophosphamide.

Results from the phase 1 study were published in Clinical Pharmacology in Drug Development in 2016.

Udenyca’s marketing authorization application is supported by data from an immunogenicity study as well as a PK/PD study comparing Udenyca (formerly CHS-1701) and Neulasta in healthy subjects.

Results from the PK/PD trial were presented at the 2017 ASCO Annual Meeting.

The applicant for Udenyca is ERA Consulting GmbH. The applicant for Pelgraz is Accord Healthcare Limited (the international arm of Intas Pharmaceuticals Ltd).

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 pegfilgrastim biosimilar candidates—Udenyca and Pelgraz.

Both products have been deemed highly similar to the reference product, Neulasta, a growth-colony-stimulating factor intended to reduce the duration of neutropenia and the incidence of febrile neutropenia due to chemotherapy.

The CHMP’s recommendations for Pelgraz and Udenyca will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Udenyca and Pelgraz will be available as 6 mg solutions for injection.

The full indication for both products will be to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies, except chronic myeloid leukemia and myelodysplastic syndromes.

The CHMP said data have shown that Pelgraz and Udenyca both have comparable quality, safety, and efficacy to Neulasta.

Pelgraz’s marketing authorization application is supported by data from a phase 1 pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy volunteers and a phase 3 study of breast cancer patients receiving docetaxel, doxorubicin, and cyclophosphamide.

Results from the phase 1 study were published in Clinical Pharmacology in Drug Development in 2016.

Udenyca’s marketing authorization application is supported by data from an immunogenicity study as well as a PK/PD study comparing Udenyca (formerly CHS-1701) and Neulasta in healthy subjects.

Results from the PK/PD trial were presented at the 2017 ASCO Annual Meeting.

The applicant for Udenyca is ERA Consulting GmbH. The applicant for Pelgraz is Accord Healthcare Limited (the international arm of Intas Pharmaceuticals Ltd).

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 pegfilgrastim biosimilar candidates—Udenyca and Pelgraz.

Both products have been deemed highly similar to the reference product, Neulasta, a growth-colony-stimulating factor intended to reduce the duration of neutropenia and the incidence of febrile neutropenia due to chemotherapy.

The CHMP’s recommendations for Pelgraz and Udenyca will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

If approved, Udenyca and Pelgraz will be available as 6 mg solutions for injection.

The full indication for both products will be to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies, except chronic myeloid leukemia and myelodysplastic syndromes.

The CHMP said data have shown that Pelgraz and Udenyca both have comparable quality, safety, and efficacy to Neulasta.

Pelgraz’s marketing authorization application is supported by data from a phase 1 pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy volunteers and a phase 3 study of breast cancer patients receiving docetaxel, doxorubicin, and cyclophosphamide.

Results from the phase 1 study were published in Clinical Pharmacology in Drug Development in 2016.

Udenyca’s marketing authorization application is supported by data from an immunogenicity study as well as a PK/PD study comparing Udenyca (formerly CHS-1701) and Neulasta in healthy subjects.

Results from the PK/PD trial were presented at the 2017 ASCO Annual Meeting.

The applicant for Udenyca is ERA Consulting GmbH. The applicant for Pelgraz is Accord Healthcare Limited (the international arm of Intas Pharmaceuticals Ltd).

Treatment with isavuconazole resolved or substantially improved invasive fungal disease among seven of eight patients receiving concomitant ibrutinib, according to the results of a small two-center study.

The combination “was well-tolerated overall,” wrote Kaelyn C. Cummins of Brigham and Women’s Hospital, together with her associates there and at the Dana-Farber Cancer Institute, Boston. Their letter to the editor was published in Leukemia & Lymphoma.

Although ibrutinib is considered less immunosuppressive than conventional chemotherapy, it has been tied to invasive fungal infections, even in seemingly low-risk patients. The preferred treatment, voriconazole, is a very strong inhibitor of cytochrome P450 systems, of which ibrutinib is a substrate. For this study, the researchers queried the pharmacy databases of their institutions to identify adults who received concomitant isavuconazole (200 mg per day) and ibrutinib between 2015 and 2018. Drug exposures were confirmed by medical record review.

Four patients experienced clinical and radiologic resolution of invasive aspergillosis, fusariosis, mucormycosis, or phaeohyphomycosis. Another three had clinical and radiologic improvement of confirmed or probable aspergillosis or histoplasmosis. One of these patients underwent five debridements for central nervous system invasive aspergillosis but had 8 months of clinical improvement between debridements. This patient’s fungal isolate remained susceptible to isavuconazole throughout treatment. The patient who did not respond at all to isavuconazole had invasive aspergillosis with recurrent brain abscesses. The fungal isolate remained susceptible to isavuconazole, and the patient switched to long-term voriconazole therapy after stopping ibrutinib.

Several adverse events occurred while patients were on concomitant therapy. One patient developed paroxysmal atrial fibrillation that persisted after stopping ibrutinib. Another had worsening of preexisting thrombocytopenia. Among four patients with electrocardiogram data, two had transient QTc prolongation. No patient died within 12 weeks of starting concomitant therapy. Two patients eventually died after their cancer progressed.

The median age of the patients was 60 years (range, 38-76 years). Five were men. Six had chronic lymphocytic leukemia (CLL) and two had marginal zone lymphoma. Two CLL patients were on ibrutinib monotherapy, two also received rituximab, one also received umbralisib, and one also received obinutuzumab. One patient with marginal zone lymphoma was on ibrutinib monotherapy, and the other received concomitant rituximab, gemcitabine, dexamethasone, and cisplatin.

Researchers should study the mechanisms by which [Bruton’s tyrosine kinase] inhibitors might increase susceptibility to fungal infections among patients with lymphoma or CLL, said Ms. Cummins and her associates. Because the CYP3A enzyme system also metabolizes PI3K and BCL-2 inhibitors, their results “could be more broadly applicable.”

Ms. Cummins had no disclosures.

SOURCE: Cummins KC et al. Leuk. Lymphoma 2018 Jul 24. doi: 10.1080/10428194.2018.1485913.

Treatment with isavuconazole resolved or substantially improved invasive fungal disease among seven of eight patients receiving concomitant ibrutinib, according to the results of a small two-center study.

The combination “was well-tolerated overall,” wrote Kaelyn C. Cummins of Brigham and Women’s Hospital, together with her associates there and at the Dana-Farber Cancer Institute, Boston. Their letter to the editor was published in Leukemia & Lymphoma.

Although ibrutinib is considered less immunosuppressive than conventional chemotherapy, it has been tied to invasive fungal infections, even in seemingly low-risk patients. The preferred treatment, voriconazole, is a very strong inhibitor of cytochrome P450 systems, of which ibrutinib is a substrate. For this study, the researchers queried the pharmacy databases of their institutions to identify adults who received concomitant isavuconazole (200 mg per day) and ibrutinib between 2015 and 2018. Drug exposures were confirmed by medical record review.

Four patients experienced clinical and radiologic resolution of invasive aspergillosis, fusariosis, mucormycosis, or phaeohyphomycosis. Another three had clinical and radiologic improvement of confirmed or probable aspergillosis or histoplasmosis. One of these patients underwent five debridements for central nervous system invasive aspergillosis but had 8 months of clinical improvement between debridements. This patient’s fungal isolate remained susceptible to isavuconazole throughout treatment. The patient who did not respond at all to isavuconazole had invasive aspergillosis with recurrent brain abscesses. The fungal isolate remained susceptible to isavuconazole, and the patient switched to long-term voriconazole therapy after stopping ibrutinib.

Several adverse events occurred while patients were on concomitant therapy. One patient developed paroxysmal atrial fibrillation that persisted after stopping ibrutinib. Another had worsening of preexisting thrombocytopenia. Among four patients with electrocardiogram data, two had transient QTc prolongation. No patient died within 12 weeks of starting concomitant therapy. Two patients eventually died after their cancer progressed.

The median age of the patients was 60 years (range, 38-76 years). Five were men. Six had chronic lymphocytic leukemia (CLL) and two had marginal zone lymphoma. Two CLL patients were on ibrutinib monotherapy, two also received rituximab, one also received umbralisib, and one also received obinutuzumab. One patient with marginal zone lymphoma was on ibrutinib monotherapy, and the other received concomitant rituximab, gemcitabine, dexamethasone, and cisplatin.

Researchers should study the mechanisms by which [Bruton’s tyrosine kinase] inhibitors might increase susceptibility to fungal infections among patients with lymphoma or CLL, said Ms. Cummins and her associates. Because the CYP3A enzyme system also metabolizes PI3K and BCL-2 inhibitors, their results “could be more broadly applicable.”

Ms. Cummins had no disclosures.

SOURCE: Cummins KC et al. Leuk. Lymphoma 2018 Jul 24. doi: 10.1080/10428194.2018.1485913.

Treatment with isavuconazole resolved or substantially improved invasive fungal disease among seven of eight patients receiving concomitant ibrutinib, according to the results of a small two-center study.

The combination “was well-tolerated overall,” wrote Kaelyn C. Cummins of Brigham and Women’s Hospital, together with her associates there and at the Dana-Farber Cancer Institute, Boston. Their letter to the editor was published in Leukemia & Lymphoma.

Although ibrutinib is considered less immunosuppressive than conventional chemotherapy, it has been tied to invasive fungal infections, even in seemingly low-risk patients. The preferred treatment, voriconazole, is a very strong inhibitor of cytochrome P450 systems, of which ibrutinib is a substrate. For this study, the researchers queried the pharmacy databases of their institutions to identify adults who received concomitant isavuconazole (200 mg per day) and ibrutinib between 2015 and 2018. Drug exposures were confirmed by medical record review.

Four patients experienced clinical and radiologic resolution of invasive aspergillosis, fusariosis, mucormycosis, or phaeohyphomycosis. Another three had clinical and radiologic improvement of confirmed or probable aspergillosis or histoplasmosis. One of these patients underwent five debridements for central nervous system invasive aspergillosis but had 8 months of clinical improvement between debridements. This patient’s fungal isolate remained susceptible to isavuconazole throughout treatment. The patient who did not respond at all to isavuconazole had invasive aspergillosis with recurrent brain abscesses. The fungal isolate remained susceptible to isavuconazole, and the patient switched to long-term voriconazole therapy after stopping ibrutinib.

Several adverse events occurred while patients were on concomitant therapy. One patient developed paroxysmal atrial fibrillation that persisted after stopping ibrutinib. Another had worsening of preexisting thrombocytopenia. Among four patients with electrocardiogram data, two had transient QTc prolongation. No patient died within 12 weeks of starting concomitant therapy. Two patients eventually died after their cancer progressed.

The median age of the patients was 60 years (range, 38-76 years). Five were men. Six had chronic lymphocytic leukemia (CLL) and two had marginal zone lymphoma. Two CLL patients were on ibrutinib monotherapy, two also received rituximab, one also received umbralisib, and one also received obinutuzumab. One patient with marginal zone lymphoma was on ibrutinib monotherapy, and the other received concomitant rituximab, gemcitabine, dexamethasone, and cisplatin.

Researchers should study the mechanisms by which [Bruton’s tyrosine kinase] inhibitors might increase susceptibility to fungal infections among patients with lymphoma or CLL, said Ms. Cummins and her associates. Because the CYP3A enzyme system also metabolizes PI3K and BCL-2 inhibitors, their results “could be more broadly applicable.”

Ms. Cummins had no disclosures.

SOURCE: Cummins KC et al. Leuk. Lymphoma 2018 Jul 24. doi: 10.1080/10428194.2018.1485913.

Photo by Rhoda Baer

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.

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.

Photo by Rhoda Baer

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.

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.

Photo by Rhoda Baer

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.

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.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted fast track designation to zanubrutinib for the treatment of Waldenström’s macroglobulinemia (WM).

Zanubrutinib (BGB-3111) is a BTK inhibitor being developed by BeiGene to treat various B-cell malignancies.

BeiGene is preparing to submit to the FDA, in the first half of 2019, a new drug application seeking accelerated approval of zanubrutinib for patients with WM.

The application will be supported by results from a phase 1 study. Results from this trial were presented at the 14th International Conference on Malignant Lymphoma (14-ICML) last year.

Researchers are also evaluating zanubrutinib in phase 2 (NCT03332173) and phase 3 (NCT03053440) trials of WM patients. In the phase 3 trial, researchers are comparing zanubrutinib to the BTK inhibitor ibrutinib.

Phase 1 results

As of March 31, 2017, 48 WM patients were enrolled in the phase 1 study. Thirty-eight patients had relapsed/refractory disease, and 10 patients were treatment-naïve.

There was a dose-escalation phase and a dose-expansion phase. The dose-expansion phase included doses of 160 mg twice a day or 320 mg once a day.

The most common (>10%) adverse events, (AEs) of any attribution were petechiae/purpura/contusion (35%), upper respiratory tract infection (31%), constipation (25%), diarrhea (19%), epistaxis (19%), nausea (17%), cough (15%), anemia (15%), headache (15%), neutropenia (13%), and rash (13%).

Most of these events were grade 1 or 2 in severity. The exceptions were grade 3/4 anemia and neutropenia (8% each) as well as grade 3/4 diarrhea and headache (2% each).

Five serious AEs were considered possibly related to zanubrutinib—1 case each of hemothorax, atrial fibrillation, colitis, febrile neutropenia, and headache. Three AEs led to treatment discontinuation—1 case each of bronchiectasis, prostate adenocarcinoma, and adenocarcinoma of pylorus.

At the time of the data cutoff, 42 patients were evaluable for response. At a median follow-up of 12.3 months (range, 4.4 to 30.5 months), the overall response rate was 90% (38/42).

The major response rate was 76% (32/42), with very good partial responses in 43% (18/42) of patients and partial responses in 33% (14/42) of patients. There were no complete responses and 2 cases of disease progression.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted fast track designation to zanubrutinib for the treatment of Waldenström’s macroglobulinemia (WM).

Zanubrutinib (BGB-3111) is a BTK inhibitor being developed by BeiGene to treat various B-cell malignancies.

BeiGene is preparing to submit to the FDA, in the first half of 2019, a new drug application seeking accelerated approval of zanubrutinib for patients with WM.

The application will be supported by results from a phase 1 study. Results from this trial were presented at the 14th International Conference on Malignant Lymphoma (14-ICML) last year.

Researchers are also evaluating zanubrutinib in phase 2 (NCT03332173) and phase 3 (NCT03053440) trials of WM patients. In the phase 3 trial, researchers are comparing zanubrutinib to the BTK inhibitor ibrutinib.

Phase 1 results

As of March 31, 2017, 48 WM patients were enrolled in the phase 1 study. Thirty-eight patients had relapsed/refractory disease, and 10 patients were treatment-naïve.

There was a dose-escalation phase and a dose-expansion phase. The dose-expansion phase included doses of 160 mg twice a day or 320 mg once a day.

The most common (>10%) adverse events, (AEs) of any attribution were petechiae/purpura/contusion (35%), upper respiratory tract infection (31%), constipation (25%), diarrhea (19%), epistaxis (19%), nausea (17%), cough (15%), anemia (15%), headache (15%), neutropenia (13%), and rash (13%).

Most of these events were grade 1 or 2 in severity. The exceptions were grade 3/4 anemia and neutropenia (8% each) as well as grade 3/4 diarrhea and headache (2% each).

Five serious AEs were considered possibly related to zanubrutinib—1 case each of hemothorax, atrial fibrillation, colitis, febrile neutropenia, and headache. Three AEs led to treatment discontinuation—1 case each of bronchiectasis, prostate adenocarcinoma, and adenocarcinoma of pylorus.

At the time of the data cutoff, 42 patients were evaluable for response. At a median follow-up of 12.3 months (range, 4.4 to 30.5 months), the overall response rate was 90% (38/42).

The major response rate was 76% (32/42), with very good partial responses in 43% (18/42) of patients and partial responses in 33% (14/42) of patients. There were no complete responses and 2 cases of disease progression.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted fast track designation to zanubrutinib for the treatment of Waldenström’s macroglobulinemia (WM).

Zanubrutinib (BGB-3111) is a BTK inhibitor being developed by BeiGene to treat various B-cell malignancies.

BeiGene is preparing to submit to the FDA, in the first half of 2019, a new drug application seeking accelerated approval of zanubrutinib for patients with WM.

The application will be supported by results from a phase 1 study. Results from this trial were presented at the 14th International Conference on Malignant Lymphoma (14-ICML) last year.

Researchers are also evaluating zanubrutinib in phase 2 (NCT03332173) and phase 3 (NCT03053440) trials of WM patients. In the phase 3 trial, researchers are comparing zanubrutinib to the BTK inhibitor ibrutinib.

Phase 1 results

As of March 31, 2017, 48 WM patients were enrolled in the phase 1 study. Thirty-eight patients had relapsed/refractory disease, and 10 patients were treatment-naïve.

There was a dose-escalation phase and a dose-expansion phase. The dose-expansion phase included doses of 160 mg twice a day or 320 mg once a day.

The most common (>10%) adverse events, (AEs) of any attribution were petechiae/purpura/contusion (35%), upper respiratory tract infection (31%), constipation (25%), diarrhea (19%), epistaxis (19%), nausea (17%), cough (15%), anemia (15%), headache (15%), neutropenia (13%), and rash (13%).

Most of these events were grade 1 or 2 in severity. The exceptions were grade 3/4 anemia and neutropenia (8% each) as well as grade 3/4 diarrhea and headache (2% each).

Five serious AEs were considered possibly related to zanubrutinib—1 case each of hemothorax, atrial fibrillation, colitis, febrile neutropenia, and headache. Three AEs led to treatment discontinuation—1 case each of bronchiectasis, prostate adenocarcinoma, and adenocarcinoma of pylorus.

At the time of the data cutoff, 42 patients were evaluable for response. At a median follow-up of 12.3 months (range, 4.4 to 30.5 months), the overall response rate was 90% (38/42).

The major response rate was 76% (32/42), with very good partial responses in 43% (18/42) of patients and partial responses in 33% (14/42) of patients. There were no complete responses and 2 cases of disease progression.

About fast track designation

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

Rituximab-based chemotherapy can significantly reduce the risk of transformation of follicular lymphoma (FL) from an indolent to an aggressive histology, such as diffuse large B-cell lymphoma, results of a retrospective pooled analysis have suggested.

Patho/Wikimedia Commons/CC BY-SA 3.0

Data on a total of 8,116 patients were available for analysis; 509 of these patients had had histologic transformations. After a median follow-up of 87 months, the 10-year cumulative hazard for all patients was 7.7%. The 10-year cumulative hazard – one of two primary endpoints – was 5.2% for patients who had received any rituximab versus 8.7% for those who did not, which translated into a hazard ratio of 0.73 (P = .004).

Among patients who received rituximab during induction only, the 10-year cumulative hazard was 5.9%, and it was 3.6% among those who received rituximab during induction and maintenance phases of treatment. This difference translated into a HR of 0.55 (P = .003).

The benefit of rituximab induction and maintenance – compared with induction only – held up in a multivariate analysis controlling for age at diagnosis, sex, FLIPI (Follicular Lymphoma International Prognostic Index) score, active surveillance vs. treatment, and FL grade (HR, 0.55; P = .016).

There were 287 deaths among the 509 patients with transformation, resulting in a 10-year survival after transformation of 32%.

The 5-year survival after transformation was 38% for patients who were not exposed to rituximab, 42% for patients who received induction rituximab, and 43% for those who received both induction and maintenance rituximab, but the differences between the three groups were not statistically significant.

“More comprehensive knowledge of the biological risk factors for follicular lymphoma transformation and the molecular pathways involved is likely to help clinicians make more accurate prognostic assessments and also inform the potential usefulness of novel drugs for the treatment of follicular lymphoma,” the researchers wrote.

SOURCE: Federico M et al. Lancet Haematol. 2018 Jul 4. doi: 10.1016/S2352-3026(18)30090-5.
 

Rituximab-based chemotherapy can significantly reduce the risk of transformation of follicular lymphoma (FL) from an indolent to an aggressive histology, such as diffuse large B-cell lymphoma, results of a retrospective pooled analysis have suggested.

Patho/Wikimedia Commons/CC BY-SA 3.0

Data on a total of 8,116 patients were available for analysis; 509 of these patients had had histologic transformations. After a median follow-up of 87 months, the 10-year cumulative hazard for all patients was 7.7%. The 10-year cumulative hazard – one of two primary endpoints – was 5.2% for patients who had received any rituximab versus 8.7% for those who did not, which translated into a hazard ratio of 0.73 (P = .004).

Among patients who received rituximab during induction only, the 10-year cumulative hazard was 5.9%, and it was 3.6% among those who received rituximab during induction and maintenance phases of treatment. This difference translated into a HR of 0.55 (P = .003).

The benefit of rituximab induction and maintenance – compared with induction only – held up in a multivariate analysis controlling for age at diagnosis, sex, FLIPI (Follicular Lymphoma International Prognostic Index) score, active surveillance vs. treatment, and FL grade (HR, 0.55; P = .016).

There were 287 deaths among the 509 patients with transformation, resulting in a 10-year survival after transformation of 32%.

The 5-year survival after transformation was 38% for patients who were not exposed to rituximab, 42% for patients who received induction rituximab, and 43% for those who received both induction and maintenance rituximab, but the differences between the three groups were not statistically significant.

“More comprehensive knowledge of the biological risk factors for follicular lymphoma transformation and the molecular pathways involved is likely to help clinicians make more accurate prognostic assessments and also inform the potential usefulness of novel drugs for the treatment of follicular lymphoma,” the researchers wrote.

SOURCE: Federico M et al. Lancet Haematol. 2018 Jul 4. doi: 10.1016/S2352-3026(18)30090-5.
 

Rituximab-based chemotherapy can significantly reduce the risk of transformation of follicular lymphoma (FL) from an indolent to an aggressive histology, such as diffuse large B-cell lymphoma, results of a retrospective pooled analysis have suggested.

Patho/Wikimedia Commons/CC BY-SA 3.0

Data on a total of 8,116 patients were available for analysis; 509 of these patients had had histologic transformations. After a median follow-up of 87 months, the 10-year cumulative hazard for all patients was 7.7%. The 10-year cumulative hazard – one of two primary endpoints – was 5.2% for patients who had received any rituximab versus 8.7% for those who did not, which translated into a hazard ratio of 0.73 (P = .004).

Among patients who received rituximab during induction only, the 10-year cumulative hazard was 5.9%, and it was 3.6% among those who received rituximab during induction and maintenance phases of treatment. This difference translated into a HR of 0.55 (P = .003).

The benefit of rituximab induction and maintenance – compared with induction only – held up in a multivariate analysis controlling for age at diagnosis, sex, FLIPI (Follicular Lymphoma International Prognostic Index) score, active surveillance vs. treatment, and FL grade (HR, 0.55; P = .016).

There were 287 deaths among the 509 patients with transformation, resulting in a 10-year survival after transformation of 32%.

The 5-year survival after transformation was 38% for patients who were not exposed to rituximab, 42% for patients who received induction rituximab, and 43% for those who received both induction and maintenance rituximab, but the differences between the three groups were not statistically significant.

“More comprehensive knowledge of the biological risk factors for follicular lymphoma transformation and the molecular pathways involved is likely to help clinicians make more accurate prognostic assessments and also inform the potential usefulness of novel drugs for the treatment of follicular lymphoma,” the researchers wrote.

SOURCE: Federico M et al. Lancet Haematol. 2018 Jul 4. doi: 10.1016/S2352-3026(18)30090-5.
 

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

STOCKHOLM –Adding the monoclonal antibody elotuzumab to pomalidomide and dexamethasone nearly doubled the overall response rate and median progression-free survival in patients with relapsed/refractory multiple myeloma compared with pomalidomide and dexamethasone alone, results of the phase 2 ELOQUENT-3 trial showed.

Neil Osterweil/MDedge News

After a minimum follow-up of 9.1 months, median progression-free survival (PFS) for 60 patients assigned to receive elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (EPd) was 10.3 months, compared with 4.7 months for 60 patients assigned to pomalidomide and dexamethasone (Pd). This difference translated into a hazard ratio (HR) of 0.54 (P = .0078) favoring EPd, reported Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens (Greece).

“The study met its primary endpoint, which was specifically designed to detect a large treatment effect in a relatively small sample of patients. Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” he said at the annual congress of the European Hematology Association.

Elotuzumab is an immunoglobulin G (IgG) monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7) expressed on multiple myeloma cells. Pomalidomide, an immunomodulator, may act synergistically with elotuzumab through several different mechanisms to increase killing of multiple myeloma cells, Dr. Dimopoulos said.

In ELOQUENT-3, patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor and no prior pomalidomide were enrolled and randomly assigned to receive either pomalidomide 4 mg orally on days 1-21 of each 28-day cycle plus oral dexamethasone 40 mg equivalent weekly, or to the same regimen plus intravenous elotuzumab 10 mg/kg weekly for cycles 1 and 2, and 20 mg/kg every 4 weeks for cycle 3 and subsequent cycles.

The trial met its primary endpoint of investigator-assessed PFS, with a 46% reduction in the risk of progression or death with EPd compared with Pd.

An analysis of PFS by subgroups showed that EPd was significantly superior to Pd for patients younger than 65 years, those with International Staging System stage I-II at study entry, patients with lactate dehydrogenase levels below 300 IU/L at baseline, patients who had two or three prior lines of therapy vs. four or more, and those who had disease that was refractory to both lenalidomide and a proteasome inhibitor.

EPd was also associated with a trend toward better PFS in an analysis combining patients with high-risk cytogenetics (deletion 17p or translocation 14;16) or high LDH levels, with a median of 7.7 months compared with 3.6 months for Pd. However, the HR, 0.55, was not statistically significant, likely because of the small sample size.

Similarly, the elotuzumab-containing combination showed a nonsignificant trend toward better PFS among patients without high risk disease, with a median PFS not reached, vs. not reached, vs. 4.7 months for patients treated with Pd.

The overall response rate with EPd was 53%, compared with 26% for Pd (odds ratio 3.5, P = .0029). The responses in the elotuzumab arm consisted of 8% complete response, 12% very good partial responses, and 33% partial responses. The respective rates in the Pd group were 2%, 7%, and 18%.

The median duration of response with EPd was not reached at the time of the database lock, compared with 8.3 months with Pd.

A preliminary analysis of overall survival showed a trend favoring EPd (13 deaths out to 22 months of follow-up, compared with 18 deaths out to 20 months in the Pd arm; HR 0.62, nonsignificant).

There were five treatment-related deaths in the EPd arm, and eight in the Pd arm. Grade 1 or 2 infusion reactions occurred in three patients in the EPd arm.

Other adverse events were comparable between the arms, with 57% of patients in the EPd arm and 60% in the Pd arm having at least one grade 3 or 4 adverse event.

“The hematologic toxicity was driven by pomalidomide and low-dose dexamethasone. For unclear reasons, there was less grade 3 or 4 neutropenia with the addition of elotuzumab to pomalidomide/dexamethasone, and also the infection rate was lower in the EPd arm,” Dr. Dimopoulos said.
 

SOURCE: Dimopoulos MA et al. EHA Congress, Abstract LB2606.

STOCKHOLM –Adding the monoclonal antibody elotuzumab to pomalidomide and dexamethasone nearly doubled the overall response rate and median progression-free survival in patients with relapsed/refractory multiple myeloma compared with pomalidomide and dexamethasone alone, results of the phase 2 ELOQUENT-3 trial showed.

Neil Osterweil/MDedge News

After a minimum follow-up of 9.1 months, median progression-free survival (PFS) for 60 patients assigned to receive elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (EPd) was 10.3 months, compared with 4.7 months for 60 patients assigned to pomalidomide and dexamethasone (Pd). This difference translated into a hazard ratio (HR) of 0.54 (P = .0078) favoring EPd, reported Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens (Greece).

“The study met its primary endpoint, which was specifically designed to detect a large treatment effect in a relatively small sample of patients. Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” he said at the annual congress of the European Hematology Association.

Elotuzumab is an immunoglobulin G (IgG) monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7) expressed on multiple myeloma cells. Pomalidomide, an immunomodulator, may act synergistically with elotuzumab through several different mechanisms to increase killing of multiple myeloma cells, Dr. Dimopoulos said.

In ELOQUENT-3, patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor and no prior pomalidomide were enrolled and randomly assigned to receive either pomalidomide 4 mg orally on days 1-21 of each 28-day cycle plus oral dexamethasone 40 mg equivalent weekly, or to the same regimen plus intravenous elotuzumab 10 mg/kg weekly for cycles 1 and 2, and 20 mg/kg every 4 weeks for cycle 3 and subsequent cycles.

The trial met its primary endpoint of investigator-assessed PFS, with a 46% reduction in the risk of progression or death with EPd compared with Pd.

An analysis of PFS by subgroups showed that EPd was significantly superior to Pd for patients younger than 65 years, those with International Staging System stage I-II at study entry, patients with lactate dehydrogenase levels below 300 IU/L at baseline, patients who had two or three prior lines of therapy vs. four or more, and those who had disease that was refractory to both lenalidomide and a proteasome inhibitor.

EPd was also associated with a trend toward better PFS in an analysis combining patients with high-risk cytogenetics (deletion 17p or translocation 14;16) or high LDH levels, with a median of 7.7 months compared with 3.6 months for Pd. However, the HR, 0.55, was not statistically significant, likely because of the small sample size.

Similarly, the elotuzumab-containing combination showed a nonsignificant trend toward better PFS among patients without high risk disease, with a median PFS not reached, vs. not reached, vs. 4.7 months for patients treated with Pd.

The overall response rate with EPd was 53%, compared with 26% for Pd (odds ratio 3.5, P = .0029). The responses in the elotuzumab arm consisted of 8% complete response, 12% very good partial responses, and 33% partial responses. The respective rates in the Pd group were 2%, 7%, and 18%.

The median duration of response with EPd was not reached at the time of the database lock, compared with 8.3 months with Pd.

A preliminary analysis of overall survival showed a trend favoring EPd (13 deaths out to 22 months of follow-up, compared with 18 deaths out to 20 months in the Pd arm; HR 0.62, nonsignificant).

There were five treatment-related deaths in the EPd arm, and eight in the Pd arm. Grade 1 or 2 infusion reactions occurred in three patients in the EPd arm.

Other adverse events were comparable between the arms, with 57% of patients in the EPd arm and 60% in the Pd arm having at least one grade 3 or 4 adverse event.

“The hematologic toxicity was driven by pomalidomide and low-dose dexamethasone. For unclear reasons, there was less grade 3 or 4 neutropenia with the addition of elotuzumab to pomalidomide/dexamethasone, and also the infection rate was lower in the EPd arm,” Dr. Dimopoulos said.
 

SOURCE: Dimopoulos MA et al. EHA Congress, Abstract LB2606.

STOCKHOLM –Adding the monoclonal antibody elotuzumab to pomalidomide and dexamethasone nearly doubled the overall response rate and median progression-free survival in patients with relapsed/refractory multiple myeloma compared with pomalidomide and dexamethasone alone, results of the phase 2 ELOQUENT-3 trial showed.

Neil Osterweil/MDedge News

After a minimum follow-up of 9.1 months, median progression-free survival (PFS) for 60 patients assigned to receive elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (EPd) was 10.3 months, compared with 4.7 months for 60 patients assigned to pomalidomide and dexamethasone (Pd). This difference translated into a hazard ratio (HR) of 0.54 (P = .0078) favoring EPd, reported Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens (Greece).

“The study met its primary endpoint, which was specifically designed to detect a large treatment effect in a relatively small sample of patients. Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” he said at the annual congress of the European Hematology Association.

Elotuzumab is an immunoglobulin G (IgG) monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7) expressed on multiple myeloma cells. Pomalidomide, an immunomodulator, may act synergistically with elotuzumab through several different mechanisms to increase killing of multiple myeloma cells, Dr. Dimopoulos said.

In ELOQUENT-3, patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor and no prior pomalidomide were enrolled and randomly assigned to receive either pomalidomide 4 mg orally on days 1-21 of each 28-day cycle plus oral dexamethasone 40 mg equivalent weekly, or to the same regimen plus intravenous elotuzumab 10 mg/kg weekly for cycles 1 and 2, and 20 mg/kg every 4 weeks for cycle 3 and subsequent cycles.

The trial met its primary endpoint of investigator-assessed PFS, with a 46% reduction in the risk of progression or death with EPd compared with Pd.

An analysis of PFS by subgroups showed that EPd was significantly superior to Pd for patients younger than 65 years, those with International Staging System stage I-II at study entry, patients with lactate dehydrogenase levels below 300 IU/L at baseline, patients who had two or three prior lines of therapy vs. four or more, and those who had disease that was refractory to both lenalidomide and a proteasome inhibitor.

EPd was also associated with a trend toward better PFS in an analysis combining patients with high-risk cytogenetics (deletion 17p or translocation 14;16) or high LDH levels, with a median of 7.7 months compared with 3.6 months for Pd. However, the HR, 0.55, was not statistically significant, likely because of the small sample size.

Similarly, the elotuzumab-containing combination showed a nonsignificant trend toward better PFS among patients without high risk disease, with a median PFS not reached, vs. not reached, vs. 4.7 months for patients treated with Pd.

The overall response rate with EPd was 53%, compared with 26% for Pd (odds ratio 3.5, P = .0029). The responses in the elotuzumab arm consisted of 8% complete response, 12% very good partial responses, and 33% partial responses. The respective rates in the Pd group were 2%, 7%, and 18%.

The median duration of response with EPd was not reached at the time of the database lock, compared with 8.3 months with Pd.

A preliminary analysis of overall survival showed a trend favoring EPd (13 deaths out to 22 months of follow-up, compared with 18 deaths out to 20 months in the Pd arm; HR 0.62, nonsignificant).

There were five treatment-related deaths in the EPd arm, and eight in the Pd arm. Grade 1 or 2 infusion reactions occurred in three patients in the EPd arm.

Other adverse events were comparable between the arms, with 57% of patients in the EPd arm and 60% in the Pd arm having at least one grade 3 or 4 adverse event.

“The hematologic toxicity was driven by pomalidomide and low-dose dexamethasone. For unclear reasons, there was less grade 3 or 4 neutropenia with the addition of elotuzumab to pomalidomide/dexamethasone, and also the infection rate was lower in the EPd arm,” Dr. Dimopoulos said.
 

SOURCE: Dimopoulos MA et al. EHA Congress, Abstract LB2606.