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CLL at ASH: A ‘mountain of data’ for targeted therapies
SAN DIEGO – There was a mountain of data presented at the annual meeting of the American Society of Hematology on the use of novel agents – both as frontline therapy and in combination – for the treatment of chronic lymphocytic leukemia (CLL).
In a video interview at the meeting, Brian T. Hill, MD, PhD, of the Cleveland Clinic and Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center, New York, summed up the key studies and what they mean in practice. They also looked ahead at what data are still missing that could aid in making important treatment decisions.
Dr. Hill highlighted the late-breaking abstract on the ECOG-ACRIN Cancer Research Group E1912 trial comparing ibrutinib-rituximab to a chemotherapy regimen of fludarabine, cyclophosphamide, and rituximab (FCR) in previously untreated patients under age 70 years (Abstract LBA-4). Not only was there a progression-free survival benefit with the use of the ibrutinib regimen, but there was an overall survival benefit as well, he noted.
Dr. Mato pointed to notable results from the Alliance A041202 trial of older patients with previously untreated disease that compared ibrutinib alone or in combination with rituximab, with bendamustine plus rituximab (Abstract #6). The ibrutinib-containing regimens resulted in superior progression-free survival.
The two trials taken together show a movement away from chemotherapy in the frontline setting and toward targeted agents for CLL, Dr. Mato said. “What that agent or combination of agents will be, remains to be seen,” he said. “We have now a real message about the fact that we’re ending, potentially, the era of chemotherapy for patients with CLL, which is a very welcome change.”
Dr. Mato and Dr. Hill will be discussing these trials and more CLL data during a Twitter chat on Jan. 31, 2019, from 7 p.m. to 8 p.m. EST. Join in the conversation by using and following #MDedgeChats.
SAN DIEGO – There was a mountain of data presented at the annual meeting of the American Society of Hematology on the use of novel agents – both as frontline therapy and in combination – for the treatment of chronic lymphocytic leukemia (CLL).
In a video interview at the meeting, Brian T. Hill, MD, PhD, of the Cleveland Clinic and Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center, New York, summed up the key studies and what they mean in practice. They also looked ahead at what data are still missing that could aid in making important treatment decisions.
Dr. Hill highlighted the late-breaking abstract on the ECOG-ACRIN Cancer Research Group E1912 trial comparing ibrutinib-rituximab to a chemotherapy regimen of fludarabine, cyclophosphamide, and rituximab (FCR) in previously untreated patients under age 70 years (Abstract LBA-4). Not only was there a progression-free survival benefit with the use of the ibrutinib regimen, but there was an overall survival benefit as well, he noted.
Dr. Mato pointed to notable results from the Alliance A041202 trial of older patients with previously untreated disease that compared ibrutinib alone or in combination with rituximab, with bendamustine plus rituximab (Abstract #6). The ibrutinib-containing regimens resulted in superior progression-free survival.
The two trials taken together show a movement away from chemotherapy in the frontline setting and toward targeted agents for CLL, Dr. Mato said. “What that agent or combination of agents will be, remains to be seen,” he said. “We have now a real message about the fact that we’re ending, potentially, the era of chemotherapy for patients with CLL, which is a very welcome change.”
Dr. Mato and Dr. Hill will be discussing these trials and more CLL data during a Twitter chat on Jan. 31, 2019, from 7 p.m. to 8 p.m. EST. Join in the conversation by using and following #MDedgeChats.
SAN DIEGO – There was a mountain of data presented at the annual meeting of the American Society of Hematology on the use of novel agents – both as frontline therapy and in combination – for the treatment of chronic lymphocytic leukemia (CLL).
In a video interview at the meeting, Brian T. Hill, MD, PhD, of the Cleveland Clinic and Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center, New York, summed up the key studies and what they mean in practice. They also looked ahead at what data are still missing that could aid in making important treatment decisions.
Dr. Hill highlighted the late-breaking abstract on the ECOG-ACRIN Cancer Research Group E1912 trial comparing ibrutinib-rituximab to a chemotherapy regimen of fludarabine, cyclophosphamide, and rituximab (FCR) in previously untreated patients under age 70 years (Abstract LBA-4). Not only was there a progression-free survival benefit with the use of the ibrutinib regimen, but there was an overall survival benefit as well, he noted.
Dr. Mato pointed to notable results from the Alliance A041202 trial of older patients with previously untreated disease that compared ibrutinib alone or in combination with rituximab, with bendamustine plus rituximab (Abstract #6). The ibrutinib-containing regimens resulted in superior progression-free survival.
The two trials taken together show a movement away from chemotherapy in the frontline setting and toward targeted agents for CLL, Dr. Mato said. “What that agent or combination of agents will be, remains to be seen,” he said. “We have now a real message about the fact that we’re ending, potentially, the era of chemotherapy for patients with CLL, which is a very welcome change.”
Dr. Mato and Dr. Hill will be discussing these trials and more CLL data during a Twitter chat on Jan. 31, 2019, from 7 p.m. to 8 p.m. EST. Join in the conversation by using and following #MDedgeChats.
REPORTING FROM ASH 2018
Phase 3 data support apixaban for cancer-associated VTE
SAN DIEGO – according to the Phase 3 ADAM VTE trial.
The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.
The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,
pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT) – 48% and 47%, respectively
- PE only – 44% and 39%, respectively
- PE with DVT – 12% in both arms
- DVT only – 37% and 35%, respectively
- Lower extremity DVT – 31% and 34%, respectively
- Upper extremity DVT – 17% and 14%, respectively
- Cerebral venous thrombosis (VT) – 1% and 0%, respectively
- Splanchnic VT – 8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).
“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
jensmith@mdedge.com
SOURCE: McBane RD et al. ASH 2018, Abstract 421.
SAN DIEGO – according to the Phase 3 ADAM VTE trial.
The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.
The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,
pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT) – 48% and 47%, respectively
- PE only – 44% and 39%, respectively
- PE with DVT – 12% in both arms
- DVT only – 37% and 35%, respectively
- Lower extremity DVT – 31% and 34%, respectively
- Upper extremity DVT – 17% and 14%, respectively
- Cerebral venous thrombosis (VT) – 1% and 0%, respectively
- Splanchnic VT – 8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).
“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
jensmith@mdedge.com
SOURCE: McBane RD et al. ASH 2018, Abstract 421.
SAN DIEGO – according to the Phase 3 ADAM VTE trial.
The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.
The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,
pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT) – 48% and 47%, respectively
- PE only – 44% and 39%, respectively
- PE with DVT – 12% in both arms
- DVT only – 37% and 35%, respectively
- Lower extremity DVT – 31% and 34%, respectively
- Upper extremity DVT – 17% and 14%, respectively
- Cerebral venous thrombosis (VT) – 1% and 0%, respectively
- Splanchnic VT – 8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).
“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
jensmith@mdedge.com
SOURCE: McBane RD et al. ASH 2018, Abstract 421.
REPORTING FROM ASH 2018
Key clinical point: Apixaban is associated with a similar risk of major bleeding and a lower risk of VTE recurrence when compared with dalteparin in patients with cancer-associated VTE.
Major finding: There were no major bleeding events in the apixaban arm and two in the dalteparin arm (P = .14).
Study details: Phase 3 study of 300 patients.
Disclosures: This study was funded by BMS/Pfizer Alliance.
Source: McBane RD et al. ASH 2018, Abstract 421.
MAIA: Daratumumab plus len-dex improves myeloma PFS
SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.
Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).
The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.
Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.
In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
MAIA details
The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.
Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.
The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.
The primary endpoint of progression-free survival was superior with DRd.
DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).
The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.
Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.
SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.
SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.
Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).
The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.
Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.
In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
MAIA details
The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.
Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.
The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.
The primary endpoint of progression-free survival was superior with DRd.
DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).
The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.
Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.
SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.
SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.
Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).
The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.
Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.
In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
MAIA details
The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.
Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.
The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.
The primary endpoint of progression-free survival was superior with DRd.
DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).
The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.
Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.
SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: At 30 months of follow-up, DRd was associated with a 44% reduction in the risk of death, compared with Rd.
Study details: Randomized phase 3 trial of 737 patients with newly diagnosed multiple myeloma who were ineligible for transplant.
Disclosures: Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.
Source: Facon T et al. ASH 2018, Abstract LBA-2.
NCI director: Data failures cost lives
SAN DIEGO – A couple years ago, hematologist-oncologist Norman E. “Ned” Sharpless, MD, was gobsmacked by a groundbreaking study into treatments for acute myeloid leukemia. While the findings offered valuable new insight into the best drug options, they left Dr. Sharpless quaking, and not with delight. “I can recall that my knees buckled,” he said. 
Why? Because the findings, he told colleagues at the annual meeting of the American Society of Hematology, came too late for many patients to benefit. “One could say that’s great news, this is medical progress,” he said. “But I saw this as a clear failure of data aggregation.”
Now, Dr. Sharpless is in a position to do more than fume and speak out. He became the director of the National Cancer Institute in 2017 and he’s made “big data” one of his four priorities for the NCI under his leadership.
“While data security is crucial, there are also costs to not aggregating data and sharing it,” he said. “It means giving patients the wrong drug, it means patients having to die.”
While Dr. Sharpless said he’s disappointed by the progress on data in medicine, he had praise to offer, too. In conversations over his first year-plus on the job, he said, he’s learned that “it’s a great time to be a cancer scientist and a cancer doctor in the United States. ... It’s undeniably a great time to be a blood doctor or blood scientist. We’re making progress at a rate that is faster and greater than at any point in my career as an oncologist. Just look at all the new stuff we’ve got!”
In hematology, great strides are being made in areas such as the treatment of leukemia and lymphoma, he said. Progress is also boosting treatment in areas such as melanoma and lung, breast, ovarian, and head and neck cancer.
“Some of you will correctly point out that this progress is not enough. In some cases, treatments are moderately effective and not curative. These are singles or even doubles, but we still need home runs. We still have too many patients dying of cancer, including blood cancer,” he said. “From my perspective, it’s important to be very clear-eyed. While we have a long way to go to end suffering in all patients, we have to be willing to admit that progress has been impressive.”
Dr. Sharpless touted the Cancer Moonshot, which will allocate $1.8 billion in federal funds for cancer research over 7 years. And he mentioned his four priority areas at NCI: Workforce development, basic science, big data, and clinical trials. Initiatives in these areas include prioritization of research by early-career investigators and increased funding for trials, he said.
As for data, he said, “I’ve been trying to explain to congressional leaders why getting control of our data is important.”
Dr. Sharpless likes to point to his own encounter in his kitchen in 2016 – the one that buckled his knees – with an issue of the New England Journal of Medicine. There he found a study that examined molecular determinants of response to decitabine in acute myeloid leukemia and myelodysplastic syndromes (N Engl J Med. 2016 Nov 24;375[21]:2023-36).
“I can still close my eyes now and literally see the faces of patients whom I gave ... a very toxic regimen, some of whom had very bad outcomes,” he said. “I know in retrospect, based on certain statistics, I probably used the wrong drug in some of these patients. If we’d been aggregating data in a deliberate way, from the get-go of AML, a result like this would have fallen out immediately. I’m concerned we’re still making these types of mistakes for other cancer subtypes today.”
Moving forward, he said, the goal is “to create large, multimodal data sets ... And put them in the cloud and make them available to the research community in the most useful format possible, in a way that’s safe and secure. We have to do these things because the costs of not harnessing data are too great.”
Dr. Sharpless reported several past financial relationships with G1 Therapeutics, Healthspan Diagnostics, and Unity Biotechnology.
SAN DIEGO – A couple years ago, hematologist-oncologist Norman E. “Ned” Sharpless, MD, was gobsmacked by a groundbreaking study into treatments for acute myeloid leukemia. While the findings offered valuable new insight into the best drug options, they left Dr. Sharpless quaking, and not with delight. “I can recall that my knees buckled,” he said.
Why? Because the findings, he told colleagues at the annual meeting of the American Society of Hematology, came too late for many patients to benefit. “One could say that’s great news, this is medical progress,” he said. “But I saw this as a clear failure of data aggregation.”
Now, Dr. Sharpless is in a position to do more than fume and speak out. He became the director of the National Cancer Institute in 2017 and he’s made “big data” one of his four priorities for the NCI under his leadership.
“While data security is crucial, there are also costs to not aggregating data and sharing it,” he said. “It means giving patients the wrong drug, it means patients having to die.”
While Dr. Sharpless said he’s disappointed by the progress on data in medicine, he had praise to offer, too. In conversations over his first year-plus on the job, he said, he’s learned that “it’s a great time to be a cancer scientist and a cancer doctor in the United States. ... It’s undeniably a great time to be a blood doctor or blood scientist. We’re making progress at a rate that is faster and greater than at any point in my career as an oncologist. Just look at all the new stuff we’ve got!”
In hematology, great strides are being made in areas such as the treatment of leukemia and lymphoma, he said. Progress is also boosting treatment in areas such as melanoma and lung, breast, ovarian, and head and neck cancer.
“Some of you will correctly point out that this progress is not enough. In some cases, treatments are moderately effective and not curative. These are singles or even doubles, but we still need home runs. We still have too many patients dying of cancer, including blood cancer,” he said. “From my perspective, it’s important to be very clear-eyed. While we have a long way to go to end suffering in all patients, we have to be willing to admit that progress has been impressive.”
Dr. Sharpless touted the Cancer Moonshot, which will allocate $1.8 billion in federal funds for cancer research over 7 years. And he mentioned his four priority areas at NCI: Workforce development, basic science, big data, and clinical trials. Initiatives in these areas include prioritization of research by early-career investigators and increased funding for trials, he said.
As for data, he said, “I’ve been trying to explain to congressional leaders why getting control of our data is important.”
Dr. Sharpless likes to point to his own encounter in his kitchen in 2016 – the one that buckled his knees – with an issue of the New England Journal of Medicine. There he found a study that examined molecular determinants of response to decitabine in acute myeloid leukemia and myelodysplastic syndromes (N Engl J Med. 2016 Nov 24;375[21]:2023-36).
“I can still close my eyes now and literally see the faces of patients whom I gave ... a very toxic regimen, some of whom had very bad outcomes,” he said. “I know in retrospect, based on certain statistics, I probably used the wrong drug in some of these patients. If we’d been aggregating data in a deliberate way, from the get-go of AML, a result like this would have fallen out immediately. I’m concerned we’re still making these types of mistakes for other cancer subtypes today.”
Moving forward, he said, the goal is “to create large, multimodal data sets ... And put them in the cloud and make them available to the research community in the most useful format possible, in a way that’s safe and secure. We have to do these things because the costs of not harnessing data are too great.”
Dr. Sharpless reported several past financial relationships with G1 Therapeutics, Healthspan Diagnostics, and Unity Biotechnology.
SAN DIEGO – A couple years ago, hematologist-oncologist Norman E. “Ned” Sharpless, MD, was gobsmacked by a groundbreaking study into treatments for acute myeloid leukemia. While the findings offered valuable new insight into the best drug options, they left Dr. Sharpless quaking, and not with delight. “I can recall that my knees buckled,” he said.
Why? Because the findings, he told colleagues at the annual meeting of the American Society of Hematology, came too late for many patients to benefit. “One could say that’s great news, this is medical progress,” he said. “But I saw this as a clear failure of data aggregation.”
Now, Dr. Sharpless is in a position to do more than fume and speak out. He became the director of the National Cancer Institute in 2017 and he’s made “big data” one of his four priorities for the NCI under his leadership.
“While data security is crucial, there are also costs to not aggregating data and sharing it,” he said. “It means giving patients the wrong drug, it means patients having to die.”
While Dr. Sharpless said he’s disappointed by the progress on data in medicine, he had praise to offer, too. In conversations over his first year-plus on the job, he said, he’s learned that “it’s a great time to be a cancer scientist and a cancer doctor in the United States. ... It’s undeniably a great time to be a blood doctor or blood scientist. We’re making progress at a rate that is faster and greater than at any point in my career as an oncologist. Just look at all the new stuff we’ve got!”
In hematology, great strides are being made in areas such as the treatment of leukemia and lymphoma, he said. Progress is also boosting treatment in areas such as melanoma and lung, breast, ovarian, and head and neck cancer.
“Some of you will correctly point out that this progress is not enough. In some cases, treatments are moderately effective and not curative. These are singles or even doubles, but we still need home runs. We still have too many patients dying of cancer, including blood cancer,” he said. “From my perspective, it’s important to be very clear-eyed. While we have a long way to go to end suffering in all patients, we have to be willing to admit that progress has been impressive.”
Dr. Sharpless touted the Cancer Moonshot, which will allocate $1.8 billion in federal funds for cancer research over 7 years. And he mentioned his four priority areas at NCI: Workforce development, basic science, big data, and clinical trials. Initiatives in these areas include prioritization of research by early-career investigators and increased funding for trials, he said.
As for data, he said, “I’ve been trying to explain to congressional leaders why getting control of our data is important.”
Dr. Sharpless likes to point to his own encounter in his kitchen in 2016 – the one that buckled his knees – with an issue of the New England Journal of Medicine. There he found a study that examined molecular determinants of response to decitabine in acute myeloid leukemia and myelodysplastic syndromes (N Engl J Med. 2016 Nov 24;375[21]:2023-36).
“I can still close my eyes now and literally see the faces of patients whom I gave ... a very toxic regimen, some of whom had very bad outcomes,” he said. “I know in retrospect, based on certain statistics, I probably used the wrong drug in some of these patients. If we’d been aggregating data in a deliberate way, from the get-go of AML, a result like this would have fallen out immediately. I’m concerned we’re still making these types of mistakes for other cancer subtypes today.”
Moving forward, he said, the goal is “to create large, multimodal data sets ... And put them in the cloud and make them available to the research community in the most useful format possible, in a way that’s safe and secure. We have to do these things because the costs of not harnessing data are too great.”
Dr. Sharpless reported several past financial relationships with G1 Therapeutics, Healthspan Diagnostics, and Unity Biotechnology.
REPORTING FROM ASH 2018
Despite risks, exercise is important for patients with sickle cell
SAN DIEGO – Don’t let all your patients with sickle cell anemia (SCA) and sickle cell trait (SCT) off the hook when it comes to exercise. That was the advice from Robert I. Liem, MD, a pediatric hematologist-oncologist who studies fitness.
While some patients may face risk, these conditions should pose less of a barrier to moderate- and even high-intensity exercise, Dr. Liem, of Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, Chicago, said at the annual meeting of the American Society of Hematology.
“Instead of just focusing on potential harms, we should consider a paradigm shift, especially in sickle cell anemia,” he said. “There, we can start to consider the benefits of exercise, which may include some disease-modifying effects.”
There have been no formal studies into whether high-intensity exercise poses harm in patients with SCA, Dr. Liem noted. Why? There are several reasons, he said, including concern that exercise could increase sickling of red blood cells and assumptions about “sedentary behavior” in SCA.
However, there are indications that factors other than SCA may be reducing fitness in this population, a fact that could potentially be reversed by exercise.
Dr. Liem led a study that found “children and young adults with SCA have reduced exercise capacity attributable to factors independent of anemia.” The study showed that peak VO2 was 30% lower in children and young adults with SCA, compared with controls (Physiol Rep. 2015. doi: 10.14814/phy2.12338).
There are many possible explanations for this, he said, including patient-related factors such as pain during exercise and poor access to fitness resources.
Another study found low fitness in 83% of adults with SCA and identified chronic anemia as the most important factor (Am J Hematol. 2014 Aug;89[8]:819-24).
In patients with sickle cell trait, which Dr. Liem said affects an estimated 6%-9% of African-Americans, early reports of sudden death appeared in the 1960s and 1970s, and recent studies have provided more insight into the risk.
In 2012, a study tracked NCAA student athletes and found that Division I football players with SCT faced a 37-fold higher risk of exertion-related death than did athletes without SCT. Five players with SCT, all black and all Division I football players, had died over a 5-year period (Br J Sports Med 2012 Apr;46[5]:325-30).
A 2016 study, meanwhile, tracked more than 47,000 black soldiers in the U.S. Army and found those with SCT didn’t face a higher risk of death although they did have a “significantly higher risk” of exertional rhabdomyolysis (N Engl J Med. 2016 Aug 4; 375[5]:435-42).
While the cause of exercise-related harm in SCT isn’t fully understood, Dr. Liem said, it’s possible that extreme states such as severe dehydration, acidosis, and hypoxemia may trigger sickling. A combination of SCT, extreme exercise, heat, and genetic predisposition could produce harm by creating a “perfect storm,” he added.
Should patients with SCA or SCT exercise? Yes, Dr. Liem said, pointing to the importance of fitness in the general population.
Exercising to volitional exhaustion appears to be safe in children and adults with SCA, he said, and lack of exercise could lead to a variety of negative effects on growth in children and on quality of life.
There are “limited but promising data” linking exercise to benefits in SCA and SCT populations, he said.
Moving forward, Dr. Liem noted that guidelines from the NCAA and National Athletic Trainers’ Association offer insight into exercise best practices in SCT. They’re designed to promote acclimation during training, access to fluids, and prompt recognition of symptoms of heat-related illness and a condition known as “exercise collapse associated with sickle trait.”
However, there are no guidelines for exercise in SCA and it’s not helpful to let patients set limits on themselves based on the symptoms they experience, he said.
Dr. Liem reported having no relevant financial disclosures.
SAN DIEGO – Don’t let all your patients with sickle cell anemia (SCA) and sickle cell trait (SCT) off the hook when it comes to exercise. That was the advice from Robert I. Liem, MD, a pediatric hematologist-oncologist who studies fitness.
While some patients may face risk, these conditions should pose less of a barrier to moderate- and even high-intensity exercise, Dr. Liem, of Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, Chicago, said at the annual meeting of the American Society of Hematology.
“Instead of just focusing on potential harms, we should consider a paradigm shift, especially in sickle cell anemia,” he said. “There, we can start to consider the benefits of exercise, which may include some disease-modifying effects.”
There have been no formal studies into whether high-intensity exercise poses harm in patients with SCA, Dr. Liem noted. Why? There are several reasons, he said, including concern that exercise could increase sickling of red blood cells and assumptions about “sedentary behavior” in SCA.
However, there are indications that factors other than SCA may be reducing fitness in this population, a fact that could potentially be reversed by exercise.
Dr. Liem led a study that found “children and young adults with SCA have reduced exercise capacity attributable to factors independent of anemia.” The study showed that peak VO2 was 30% lower in children and young adults with SCA, compared with controls (Physiol Rep. 2015. doi: 10.14814/phy2.12338).
There are many possible explanations for this, he said, including patient-related factors such as pain during exercise and poor access to fitness resources.
Another study found low fitness in 83% of adults with SCA and identified chronic anemia as the most important factor (Am J Hematol. 2014 Aug;89[8]:819-24).
In patients with sickle cell trait, which Dr. Liem said affects an estimated 6%-9% of African-Americans, early reports of sudden death appeared in the 1960s and 1970s, and recent studies have provided more insight into the risk.
In 2012, a study tracked NCAA student athletes and found that Division I football players with SCT faced a 37-fold higher risk of exertion-related death than did athletes without SCT. Five players with SCT, all black and all Division I football players, had died over a 5-year period (Br J Sports Med 2012 Apr;46[5]:325-30).
A 2016 study, meanwhile, tracked more than 47,000 black soldiers in the U.S. Army and found those with SCT didn’t face a higher risk of death although they did have a “significantly higher risk” of exertional rhabdomyolysis (N Engl J Med. 2016 Aug 4; 375[5]:435-42).
While the cause of exercise-related harm in SCT isn’t fully understood, Dr. Liem said, it’s possible that extreme states such as severe dehydration, acidosis, and hypoxemia may trigger sickling. A combination of SCT, extreme exercise, heat, and genetic predisposition could produce harm by creating a “perfect storm,” he added.
Should patients with SCA or SCT exercise? Yes, Dr. Liem said, pointing to the importance of fitness in the general population.
Exercising to volitional exhaustion appears to be safe in children and adults with SCA, he said, and lack of exercise could lead to a variety of negative effects on growth in children and on quality of life.
There are “limited but promising data” linking exercise to benefits in SCA and SCT populations, he said.
Moving forward, Dr. Liem noted that guidelines from the NCAA and National Athletic Trainers’ Association offer insight into exercise best practices in SCT. They’re designed to promote acclimation during training, access to fluids, and prompt recognition of symptoms of heat-related illness and a condition known as “exercise collapse associated with sickle trait.”
However, there are no guidelines for exercise in SCA and it’s not helpful to let patients set limits on themselves based on the symptoms they experience, he said.
Dr. Liem reported having no relevant financial disclosures.
SAN DIEGO – Don’t let all your patients with sickle cell anemia (SCA) and sickle cell trait (SCT) off the hook when it comes to exercise. That was the advice from Robert I. Liem, MD, a pediatric hematologist-oncologist who studies fitness.
While some patients may face risk, these conditions should pose less of a barrier to moderate- and even high-intensity exercise, Dr. Liem, of Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, Chicago, said at the annual meeting of the American Society of Hematology.
“Instead of just focusing on potential harms, we should consider a paradigm shift, especially in sickle cell anemia,” he said. “There, we can start to consider the benefits of exercise, which may include some disease-modifying effects.”
There have been no formal studies into whether high-intensity exercise poses harm in patients with SCA, Dr. Liem noted. Why? There are several reasons, he said, including concern that exercise could increase sickling of red blood cells and assumptions about “sedentary behavior” in SCA.
However, there are indications that factors other than SCA may be reducing fitness in this population, a fact that could potentially be reversed by exercise.
Dr. Liem led a study that found “children and young adults with SCA have reduced exercise capacity attributable to factors independent of anemia.” The study showed that peak VO2 was 30% lower in children and young adults with SCA, compared with controls (Physiol Rep. 2015. doi: 10.14814/phy2.12338).
There are many possible explanations for this, he said, including patient-related factors such as pain during exercise and poor access to fitness resources.
Another study found low fitness in 83% of adults with SCA and identified chronic anemia as the most important factor (Am J Hematol. 2014 Aug;89[8]:819-24).
In patients with sickle cell trait, which Dr. Liem said affects an estimated 6%-9% of African-Americans, early reports of sudden death appeared in the 1960s and 1970s, and recent studies have provided more insight into the risk.
In 2012, a study tracked NCAA student athletes and found that Division I football players with SCT faced a 37-fold higher risk of exertion-related death than did athletes without SCT. Five players with SCT, all black and all Division I football players, had died over a 5-year period (Br J Sports Med 2012 Apr;46[5]:325-30).
A 2016 study, meanwhile, tracked more than 47,000 black soldiers in the U.S. Army and found those with SCT didn’t face a higher risk of death although they did have a “significantly higher risk” of exertional rhabdomyolysis (N Engl J Med. 2016 Aug 4; 375[5]:435-42).
While the cause of exercise-related harm in SCT isn’t fully understood, Dr. Liem said, it’s possible that extreme states such as severe dehydration, acidosis, and hypoxemia may trigger sickling. A combination of SCT, extreme exercise, heat, and genetic predisposition could produce harm by creating a “perfect storm,” he added.
Should patients with SCA or SCT exercise? Yes, Dr. Liem said, pointing to the importance of fitness in the general population.
Exercising to volitional exhaustion appears to be safe in children and adults with SCA, he said, and lack of exercise could lead to a variety of negative effects on growth in children and on quality of life.
There are “limited but promising data” linking exercise to benefits in SCA and SCT populations, he said.
Moving forward, Dr. Liem noted that guidelines from the NCAA and National Athletic Trainers’ Association offer insight into exercise best practices in SCT. They’re designed to promote acclimation during training, access to fluids, and prompt recognition of symptoms of heat-related illness and a condition known as “exercise collapse associated with sickle trait.”
However, there are no guidelines for exercise in SCA and it’s not helpful to let patients set limits on themselves based on the symptoms they experience, he said.
Dr. Liem reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM ASH 2018
Social media can help doctors stay up to date
SAN DIEGO –
“People want to see that you’re a person and not strictly a physician,” said Dr. Yates, a pediatric hematologist at Texas Children’s Hospital in Houston, who has had an active Twitter presence for the last few years.
Dr. Yates – whose Twitter handle is @sicklecelldoc – said she dipped a toe in the social media waters because she wanted to bring accurate medical information to patients in the arena where they are seeking information.
“I want families to understand their condition as well as they can on whatever level they can, and so I just found this to be another way to do that ... outside of my clinic,” she said during an interview at the annual meeting of the American Society of Hematology.
But beyond correcting misinformation and serving as an advocate for patients, Dr. Yates said she gets professional benefits from being on Twitter. For instance, she uses the platform to find relevant articles as soon as they publish, without wading through all the journals.
“It’s allowed me to kind of streamline what I read,” she said.
Dr. Yates said Twitter is her social media platform of choice because it provides a simple, succinct way to communicate and provide links to more in-depth resources.
While social media can be fun and rewarding for physicians, Dr. Yates said think before you post. Ask yourself, “would you tell your chairperson this?”
Dr. Yates reported having no relevant financial disclosures.
SAN DIEGO –
“People want to see that you’re a person and not strictly a physician,” said Dr. Yates, a pediatric hematologist at Texas Children’s Hospital in Houston, who has had an active Twitter presence for the last few years.
Dr. Yates – whose Twitter handle is @sicklecelldoc – said she dipped a toe in the social media waters because she wanted to bring accurate medical information to patients in the arena where they are seeking information.
“I want families to understand their condition as well as they can on whatever level they can, and so I just found this to be another way to do that ... outside of my clinic,” she said during an interview at the annual meeting of the American Society of Hematology.
But beyond correcting misinformation and serving as an advocate for patients, Dr. Yates said she gets professional benefits from being on Twitter. For instance, she uses the platform to find relevant articles as soon as they publish, without wading through all the journals.
“It’s allowed me to kind of streamline what I read,” she said.
Dr. Yates said Twitter is her social media platform of choice because it provides a simple, succinct way to communicate and provide links to more in-depth resources.
While social media can be fun and rewarding for physicians, Dr. Yates said think before you post. Ask yourself, “would you tell your chairperson this?”
Dr. Yates reported having no relevant financial disclosures.
SAN DIEGO –
“People want to see that you’re a person and not strictly a physician,” said Dr. Yates, a pediatric hematologist at Texas Children’s Hospital in Houston, who has had an active Twitter presence for the last few years.
Dr. Yates – whose Twitter handle is @sicklecelldoc – said she dipped a toe in the social media waters because she wanted to bring accurate medical information to patients in the arena where they are seeking information.
“I want families to understand their condition as well as they can on whatever level they can, and so I just found this to be another way to do that ... outside of my clinic,” she said during an interview at the annual meeting of the American Society of Hematology.
But beyond correcting misinformation and serving as an advocate for patients, Dr. Yates said she gets professional benefits from being on Twitter. For instance, she uses the platform to find relevant articles as soon as they publish, without wading through all the journals.
“It’s allowed me to kind of streamline what I read,” she said.
Dr. Yates said Twitter is her social media platform of choice because it provides a simple, succinct way to communicate and provide links to more in-depth resources.
While social media can be fun and rewarding for physicians, Dr. Yates said think before you post. Ask yourself, “would you tell your chairperson this?”
Dr. Yates reported having no relevant financial disclosures.
REPORTING FROM ASH 2018
Ibrutinib-rituximab ‘new standard of care’ in younger CLL patients
SAN DIEGO – The combination of ibrutinib and rituximab was associated with a two-thirds reduction in chronic lymphocytic leukemia (CLL) progression, compared with standard chemoimmunotherapy in patients younger than 70 years old, interim results of a phase 3 randomized trial showed.
Among 529 patients with previously untreated, symptomatic CLL randomly assigned to ibrutinib-rituximab (IR) or to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), the IR regimen was associated with a 65% reduction in risk for disease progression, which was the trial’s primary endpoint.
The IR regimen was also associated with better overall survival out to 4 years of follow-up, reported Tait D. Shanafelt, MD, of Stanford (Calif.) University.
“This establishes ibrutinib-based therapy as the most effective treatment tested to date in this disease for untreated patients,” he said at a media briefing prior at the annual meeting of the American Society of Hematology.
The study results are likely to dethrone FCR as the most active chemoimmunotherapy regimen against CLL, Dr. Shanafelt said.
In the ECOG-ACRIN Cancer Research Group E1912 trial, 529 patients aged 70 or younger with previously untreated CLL were enrolled and randomly assigned on a 2:1 basis to either standard therapy with six cycles of FCR according to standard protocols (175 patients), or IR, with ibrutinib 420 mg daily for each cycle, and rituximab delivered 50 mg/m2 intravenously on day 1 of cycle 2, and 325 mg/m2 on day 2 of the same cycle, and 500 mg/m2 on day 1 for all remaining cycles (354 patients).
From cycle 8 until progression, patients in the IR arm received daily ibrutinib 420 mg.
Dr. Shanafelt presented results from both an intention-to-treat analysis and a per-protocol analysis excluding 22 patients in the IR arm and 9 patients in the FCR arm who were randomized but later found not to meet eligibility criteria.
After a mean follow-up of 34 months, there were 37 PFS events in the IR arm, compared with 40 events in the FCR arm in an intention-to-treat analysis. The difference translated into a hazard ratio for progression of 0.35 with IR (P less than .00001).
The results were similar in the per-protocol analysis, with an HR of 0.32 favoring IR (P less than .00001).*
There were four deaths in the IR arm, compared with 10 in the FCR arm at the time of the data lock, translating into a hazard ratio (HR) for overall survival of 0.17 (P less than .0003) in the intention-to-treat analysis, and 0.13 in the per-protocol analysis (P less than .0001).
Dr. Shanafelt noted that although the overall number of deaths was relatively small, there were twice as many patients enrolled in the IR arm as in the FCR arm, meaning that the rate of deaths in the FCR arm was fivefold higher than in the IR arm.
In a subgroup analysis of PFS, IR was superior to FCR regardless of patient age, sex, performance status, disease stage, or the presence or absence of the 11q23.3 deletion.
PFS was also significantly better with IR in patients with unmutated immunoglobulin heavy chain variable (IGHV) regions (HR 0.26, P less than .00001), but not in patients with mutated IGHV.*
Grade 3 or greater treatment-related adverse events occurred in 58.5% of patients in the IR arm, compared with 72.1% of patients in the FCR arm. Specific events that occurred significantly less often with IR included neutropenia (22.7% vs. 43.7%), anemia (2.6% vs. 12.0%), thrombocytopenia (2.9% vs. 13.9%), any infection (7.1% vs. 19.0%), and neutropenic fever (2.3% vs. 15.8%; P less than .001 for all comparisons).
Events that occurred more frequently with IR than FCR included atrial fibrillation (2.9% vs. 0%, P = .04), and hypertension (7.4% vs. 1.9%, P = .01).
Dr. Shanafelt acknowledged that one possible barrier to the IR regimen is cost; the monthly cost of ibrutinib maintenance is about $10,000, he said, although he noted that cost considerations were not studied in the trial.
“Future trials testing novel agent combinations to see if we can eliminate the need for chronic therapy should be pursued,” he said.
The trial was sponsored by the National Cancer Institute with additional support from Pharmacyclics. Dr. Shanafelt reported patents and royalties from the Mayo Clinic, and research funding from Celgene, GlaxoSmithKline, Genentech, Abbvie, Pharmacyclics, and Janssen.
SOURCE: Shanafelt TD et al. ASH 2018, Abstract LBA-4.
*Correction, 12/12/2018: An earlier version of this story misstated the P value in two comparisons.
SAN DIEGO – The combination of ibrutinib and rituximab was associated with a two-thirds reduction in chronic lymphocytic leukemia (CLL) progression, compared with standard chemoimmunotherapy in patients younger than 70 years old, interim results of a phase 3 randomized trial showed.
Among 529 patients with previously untreated, symptomatic CLL randomly assigned to ibrutinib-rituximab (IR) or to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), the IR regimen was associated with a 65% reduction in risk for disease progression, which was the trial’s primary endpoint.
The IR regimen was also associated with better overall survival out to 4 years of follow-up, reported Tait D. Shanafelt, MD, of Stanford (Calif.) University.
“This establishes ibrutinib-based therapy as the most effective treatment tested to date in this disease for untreated patients,” he said at a media briefing prior at the annual meeting of the American Society of Hematology.
The study results are likely to dethrone FCR as the most active chemoimmunotherapy regimen against CLL, Dr. Shanafelt said.
In the ECOG-ACRIN Cancer Research Group E1912 trial, 529 patients aged 70 or younger with previously untreated CLL were enrolled and randomly assigned on a 2:1 basis to either standard therapy with six cycles of FCR according to standard protocols (175 patients), or IR, with ibrutinib 420 mg daily for each cycle, and rituximab delivered 50 mg/m2 intravenously on day 1 of cycle 2, and 325 mg/m2 on day 2 of the same cycle, and 500 mg/m2 on day 1 for all remaining cycles (354 patients).
From cycle 8 until progression, patients in the IR arm received daily ibrutinib 420 mg.
Dr. Shanafelt presented results from both an intention-to-treat analysis and a per-protocol analysis excluding 22 patients in the IR arm and 9 patients in the FCR arm who were randomized but later found not to meet eligibility criteria.
After a mean follow-up of 34 months, there were 37 PFS events in the IR arm, compared with 40 events in the FCR arm in an intention-to-treat analysis. The difference translated into a hazard ratio for progression of 0.35 with IR (P less than .00001).
The results were similar in the per-protocol analysis, with an HR of 0.32 favoring IR (P less than .00001).*
There were four deaths in the IR arm, compared with 10 in the FCR arm at the time of the data lock, translating into a hazard ratio (HR) for overall survival of 0.17 (P less than .0003) in the intention-to-treat analysis, and 0.13 in the per-protocol analysis (P less than .0001).
Dr. Shanafelt noted that although the overall number of deaths was relatively small, there were twice as many patients enrolled in the IR arm as in the FCR arm, meaning that the rate of deaths in the FCR arm was fivefold higher than in the IR arm.
In a subgroup analysis of PFS, IR was superior to FCR regardless of patient age, sex, performance status, disease stage, or the presence or absence of the 11q23.3 deletion.
PFS was also significantly better with IR in patients with unmutated immunoglobulin heavy chain variable (IGHV) regions (HR 0.26, P less than .00001), but not in patients with mutated IGHV.*
Grade 3 or greater treatment-related adverse events occurred in 58.5% of patients in the IR arm, compared with 72.1% of patients in the FCR arm. Specific events that occurred significantly less often with IR included neutropenia (22.7% vs. 43.7%), anemia (2.6% vs. 12.0%), thrombocytopenia (2.9% vs. 13.9%), any infection (7.1% vs. 19.0%), and neutropenic fever (2.3% vs. 15.8%; P less than .001 for all comparisons).
Events that occurred more frequently with IR than FCR included atrial fibrillation (2.9% vs. 0%, P = .04), and hypertension (7.4% vs. 1.9%, P = .01).
Dr. Shanafelt acknowledged that one possible barrier to the IR regimen is cost; the monthly cost of ibrutinib maintenance is about $10,000, he said, although he noted that cost considerations were not studied in the trial.
“Future trials testing novel agent combinations to see if we can eliminate the need for chronic therapy should be pursued,” he said.
The trial was sponsored by the National Cancer Institute with additional support from Pharmacyclics. Dr. Shanafelt reported patents and royalties from the Mayo Clinic, and research funding from Celgene, GlaxoSmithKline, Genentech, Abbvie, Pharmacyclics, and Janssen.
SOURCE: Shanafelt TD et al. ASH 2018, Abstract LBA-4.
*Correction, 12/12/2018: An earlier version of this story misstated the P value in two comparisons.
SAN DIEGO – The combination of ibrutinib and rituximab was associated with a two-thirds reduction in chronic lymphocytic leukemia (CLL) progression, compared with standard chemoimmunotherapy in patients younger than 70 years old, interim results of a phase 3 randomized trial showed.
Among 529 patients with previously untreated, symptomatic CLL randomly assigned to ibrutinib-rituximab (IR) or to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), the IR regimen was associated with a 65% reduction in risk for disease progression, which was the trial’s primary endpoint.
The IR regimen was also associated with better overall survival out to 4 years of follow-up, reported Tait D. Shanafelt, MD, of Stanford (Calif.) University.
“This establishes ibrutinib-based therapy as the most effective treatment tested to date in this disease for untreated patients,” he said at a media briefing prior at the annual meeting of the American Society of Hematology.
The study results are likely to dethrone FCR as the most active chemoimmunotherapy regimen against CLL, Dr. Shanafelt said.
In the ECOG-ACRIN Cancer Research Group E1912 trial, 529 patients aged 70 or younger with previously untreated CLL were enrolled and randomly assigned on a 2:1 basis to either standard therapy with six cycles of FCR according to standard protocols (175 patients), or IR, with ibrutinib 420 mg daily for each cycle, and rituximab delivered 50 mg/m2 intravenously on day 1 of cycle 2, and 325 mg/m2 on day 2 of the same cycle, and 500 mg/m2 on day 1 for all remaining cycles (354 patients).
From cycle 8 until progression, patients in the IR arm received daily ibrutinib 420 mg.
Dr. Shanafelt presented results from both an intention-to-treat analysis and a per-protocol analysis excluding 22 patients in the IR arm and 9 patients in the FCR arm who were randomized but later found not to meet eligibility criteria.
After a mean follow-up of 34 months, there were 37 PFS events in the IR arm, compared with 40 events in the FCR arm in an intention-to-treat analysis. The difference translated into a hazard ratio for progression of 0.35 with IR (P less than .00001).
The results were similar in the per-protocol analysis, with an HR of 0.32 favoring IR (P less than .00001).*
There were four deaths in the IR arm, compared with 10 in the FCR arm at the time of the data lock, translating into a hazard ratio (HR) for overall survival of 0.17 (P less than .0003) in the intention-to-treat analysis, and 0.13 in the per-protocol analysis (P less than .0001).
Dr. Shanafelt noted that although the overall number of deaths was relatively small, there were twice as many patients enrolled in the IR arm as in the FCR arm, meaning that the rate of deaths in the FCR arm was fivefold higher than in the IR arm.
In a subgroup analysis of PFS, IR was superior to FCR regardless of patient age, sex, performance status, disease stage, or the presence or absence of the 11q23.3 deletion.
PFS was also significantly better with IR in patients with unmutated immunoglobulin heavy chain variable (IGHV) regions (HR 0.26, P less than .00001), but not in patients with mutated IGHV.*
Grade 3 or greater treatment-related adverse events occurred in 58.5% of patients in the IR arm, compared with 72.1% of patients in the FCR arm. Specific events that occurred significantly less often with IR included neutropenia (22.7% vs. 43.7%), anemia (2.6% vs. 12.0%), thrombocytopenia (2.9% vs. 13.9%), any infection (7.1% vs. 19.0%), and neutropenic fever (2.3% vs. 15.8%; P less than .001 for all comparisons).
Events that occurred more frequently with IR than FCR included atrial fibrillation (2.9% vs. 0%, P = .04), and hypertension (7.4% vs. 1.9%, P = .01).
Dr. Shanafelt acknowledged that one possible barrier to the IR regimen is cost; the monthly cost of ibrutinib maintenance is about $10,000, he said, although he noted that cost considerations were not studied in the trial.
“Future trials testing novel agent combinations to see if we can eliminate the need for chronic therapy should be pursued,” he said.
The trial was sponsored by the National Cancer Institute with additional support from Pharmacyclics. Dr. Shanafelt reported patents and royalties from the Mayo Clinic, and research funding from Celgene, GlaxoSmithKline, Genentech, Abbvie, Pharmacyclics, and Janssen.
SOURCE: Shanafelt TD et al. ASH 2018, Abstract LBA-4.
*Correction, 12/12/2018: An earlier version of this story misstated the P value in two comparisons.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: The hazard ratio for disease progression with IR versus FCR was 0.35 (P less than .00001).
Study details: Interim analysis of a phase 3 trial in 529 patients aged 70 or younger with newly diagnosed CLL.
Disclosures: The trial was sponsored by the National Cancer Institute with additional support from Pharmacyclics. Dr. Shanafelt reported patents and royalties from the Mayo Clinic, and research funding from Celgene, GlaxoSmithKline, Genentech, Abbvie, Pharmacyclics, and Janssen.
Source: Shanafelt TD et al. ASH 2018, Abstract LBA-4.
Tom Brokaw opens up on surviving multiple myeloma
SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.
“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”
Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”
Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.
In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.
In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”
“There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”
At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”
He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”
“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.
Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”
SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.
“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”
Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”
Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.
In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.
In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”
“There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”
At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”
He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”
“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.
Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”
SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.
“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”
Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”
Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.
In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.
In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”
“There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”
At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”
He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”
“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.
Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”
EXPERT ANALYSIS FROM ASH 2018
Rapid test could solve Africa’s sickle cell screening problem
SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.
The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.
Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.
“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.
Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.
Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.
“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.
Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.
In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.
The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.
Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.
Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).
Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.
Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.
On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.
This article was updated on 3/14/2019.
SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.
SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.
The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.
Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.
“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.
Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.
Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.
“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.
Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.
In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.
The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.
Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.
Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).
Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.
Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.
On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.
This article was updated on 3/14/2019.
SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.
SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.
The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.
Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.
“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.
Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.
Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.
“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.
Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.
In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.
The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.
Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.
Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).
Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.
Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.
On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.
This article was updated on 3/14/2019.
SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: The assay had an overall accuracy of 99.8% in correctly identifying phenotypes as initially determined by hemoglobin electrophoresis.
Study details: A diagnostic accuracy study including 1,000 children aged 5 years and younger were prospectively recruited from hospitals and outpatient clinics in Uganda.
Disclosures: Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study and makes the test.
Source: Serrao E et al. ASH 2018, Abstract LBA-3.
Rivaroxaban may reduce VTE risk in cancer patients
SAN DIEGO – Prophylaxis with rivaroxaban significantly reduced the rate of venous thromboembolism and associated death in high-risk ambulatory cancer patients receiving systemic therapy, results of a randomized trial show.
The reduction in venous thromboembolism (VTE) or VTE-related death was not statistically significant in the primary analysis, in part because a large proportion of patients stopped taking the direct oral anticoagulant, according to investigator Alok A. Khorana, MD, of the Cleveland Clinic.
However, the reduction in events was significant in a prespecified secondary analysis limited to the on-treatment period, Dr. Khorana reported at the annual meeting of the American Society of Hematology, adding that rates of major and nonmajor bleeding were low.
Results are “eagerly awaited” from a different prophylaxis trial – the AVERT study – looking at another direct oral anticoagulant in high-risk cancer patients, Dr. Khorana said in a late-breaking abstracts session.
“If the findings of that trial are consistent with ours, then we certainly hope that these findings should inform future recommendations regarding thromboprophylaxis for high-risk ambulatory cancer patients, and then the landscape of anticoagulation in the cancer population should start to shift from management of events to primary prevention,” he said.
In the study by Dr. Khorana and his colleagues, known as CASSINI, 841 patients with various solid tumors and lymphomas were randomized to either rivaroxaban 10 mg or placebo once daily. The patients, enrolled at 143 study centers in 11 countries, all had a Khorana risk score of 2 or greater.
In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio, 0.66; 95% confidence interval, 0.40-1.09; P = .101). However, a total of 177 patients (43.7%) stopped rivaroxaban earlier than 180 days, and likewise, 203 patients (50.2%) stopped placebo early.
In a prespecified secondary analysis looking just at the period of time when patients were actually taking rivaroxaban or placebo, rivaroxaban did significantly reduce risk of VTE or VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of the rivaroxaban patients and 6.41% of placebo patients in that on-treatment analysis (HR, 0.40; 95% CI, 0.20-0.80; P = .007).
Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between groups, according to results of a safety analysis. Major bleeding occurred in eight rivaroxaban patients and four placebo patients, or 1.98% and 0.99%, respectively (P = .265).
CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported disclosures related to Janssen, Bayer, PAREXEL, Sanofi, Pfizer, TriSalus Life Sciences, Halozyme, Seattle Genetics, AngioDynamics, and others.
SAN DIEGO – Prophylaxis with rivaroxaban significantly reduced the rate of venous thromboembolism and associated death in high-risk ambulatory cancer patients receiving systemic therapy, results of a randomized trial show.
The reduction in venous thromboembolism (VTE) or VTE-related death was not statistically significant in the primary analysis, in part because a large proportion of patients stopped taking the direct oral anticoagulant, according to investigator Alok A. Khorana, MD, of the Cleveland Clinic.
However, the reduction in events was significant in a prespecified secondary analysis limited to the on-treatment period, Dr. Khorana reported at the annual meeting of the American Society of Hematology, adding that rates of major and nonmajor bleeding were low.
Results are “eagerly awaited” from a different prophylaxis trial – the AVERT study – looking at another direct oral anticoagulant in high-risk cancer patients, Dr. Khorana said in a late-breaking abstracts session.
“If the findings of that trial are consistent with ours, then we certainly hope that these findings should inform future recommendations regarding thromboprophylaxis for high-risk ambulatory cancer patients, and then the landscape of anticoagulation in the cancer population should start to shift from management of events to primary prevention,” he said.
In the study by Dr. Khorana and his colleagues, known as CASSINI, 841 patients with various solid tumors and lymphomas were randomized to either rivaroxaban 10 mg or placebo once daily. The patients, enrolled at 143 study centers in 11 countries, all had a Khorana risk score of 2 or greater.
In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio, 0.66; 95% confidence interval, 0.40-1.09; P = .101). However, a total of 177 patients (43.7%) stopped rivaroxaban earlier than 180 days, and likewise, 203 patients (50.2%) stopped placebo early.
In a prespecified secondary analysis looking just at the period of time when patients were actually taking rivaroxaban or placebo, rivaroxaban did significantly reduce risk of VTE or VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of the rivaroxaban patients and 6.41% of placebo patients in that on-treatment analysis (HR, 0.40; 95% CI, 0.20-0.80; P = .007).
Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between groups, according to results of a safety analysis. Major bleeding occurred in eight rivaroxaban patients and four placebo patients, or 1.98% and 0.99%, respectively (P = .265).
CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported disclosures related to Janssen, Bayer, PAREXEL, Sanofi, Pfizer, TriSalus Life Sciences, Halozyme, Seattle Genetics, AngioDynamics, and others.
SAN DIEGO – Prophylaxis with rivaroxaban significantly reduced the rate of venous thromboembolism and associated death in high-risk ambulatory cancer patients receiving systemic therapy, results of a randomized trial show.
The reduction in venous thromboembolism (VTE) or VTE-related death was not statistically significant in the primary analysis, in part because a large proportion of patients stopped taking the direct oral anticoagulant, according to investigator Alok A. Khorana, MD, of the Cleveland Clinic.
However, the reduction in events was significant in a prespecified secondary analysis limited to the on-treatment period, Dr. Khorana reported at the annual meeting of the American Society of Hematology, adding that rates of major and nonmajor bleeding were low.
Results are “eagerly awaited” from a different prophylaxis trial – the AVERT study – looking at another direct oral anticoagulant in high-risk cancer patients, Dr. Khorana said in a late-breaking abstracts session.
“If the findings of that trial are consistent with ours, then we certainly hope that these findings should inform future recommendations regarding thromboprophylaxis for high-risk ambulatory cancer patients, and then the landscape of anticoagulation in the cancer population should start to shift from management of events to primary prevention,” he said.
In the study by Dr. Khorana and his colleagues, known as CASSINI, 841 patients with various solid tumors and lymphomas were randomized to either rivaroxaban 10 mg or placebo once daily. The patients, enrolled at 143 study centers in 11 countries, all had a Khorana risk score of 2 or greater.
In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio, 0.66; 95% confidence interval, 0.40-1.09; P = .101). However, a total of 177 patients (43.7%) stopped rivaroxaban earlier than 180 days, and likewise, 203 patients (50.2%) stopped placebo early.
In a prespecified secondary analysis looking just at the period of time when patients were actually taking rivaroxaban or placebo, rivaroxaban did significantly reduce risk of VTE or VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of the rivaroxaban patients and 6.41% of placebo patients in that on-treatment analysis (HR, 0.40; 95% CI, 0.20-0.80; P = .007).
Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between groups, according to results of a safety analysis. Major bleeding occurred in eight rivaroxaban patients and four placebo patients, or 1.98% and 0.99%, respectively (P = .265).
CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported disclosures related to Janssen, Bayer, PAREXEL, Sanofi, Pfizer, TriSalus Life Sciences, Halozyme, Seattle Genetics, AngioDynamics, and others.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: In an on-treatment analysis, the composite endpoint occurred in 2.62% of the rivaroxaban patients and 6.41% of placebo patients (hazard ratio, 0.40; 95% confidence interval, 0.20-0.80; P = .007).
Study details: The results from CASSINI included 841 patients with various solid tumors and lymphomas randomized to rivaroxaban or placebo daily.
Disclosures: CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported disclosures related to Janssen, Bayer, PAREXEL, Sanofi, Pfizer, TriSalus Life Sciences, Halozyme, Seattle Genetics, AngioDynamics, and others.
