This slide show highlights some of the top news of 2016 on hematologic malignancies, including FDA approvals for myeloma, lymphoma, and leukemia, and studies on transplantation, risk of recurrence in AML patients, and more.
Ofatumumab Approved as Maintenance Therapy for CLL:
The US Food and Drug Administration granted approval to the CD20-targeting monoclonal antibody ofatumumab (Arzerra) for the treatment of patients with recurrent or progressive chronic lymphocytic leukemia (CLL) in complete or partial remission after two or more lines of prior therapy. The approval was based on results of the phase III PROLONG study, which included 474 patients with CLL in complete or partial remission after second- or third-line therapies. Patients were randomly assigned to receive maintenance therapy with ofatumumab (n = 238) for 2 years or observation (n = 236). With a median follow-up of close to 20 months, patients assigned ofatumumab had a median progression-free survival of 29.4 months compared with 15.2 months in patients assigned observation (hazard ratio, 0.50; 95% CI, 0.38–0.66;
. Image courtesy of Novartis.
At 5 Years, Nilotinib Offers Benefit Over Imatinib in CML:
Five-year results of the randomized phase III ENESTnd trial showed a positive risk-benefit profile for nilotinib in patients with chronic myeloid leukemia (CML) in chronic phase, as compared with imatinib. Cardiovascular risk does seem to be slightly raised with nilotinib, but improvements in CML disease control likely outweigh those risks. At 5 years, 217 patients (77%) in the lower dose nilotinib group (300 mg twice daily) achieved a major molecular response (MMR), and 217 patients (77.2%) in the higher dose nilotinib group (400 mg twice daily) achieved MMR; 171 imatinib patients (60.4) achieved MMR (400 mg once daily). Progression to accelerated or blast phase was more likely with imatinib than with nilotinib.
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Increased Adolescent Body Weight Linked to NHL:
Individuals with increased body mass index (BMI) during adolescence showed an increased association with a diagnosis of non-Hodgkin lymphoma (NHL), according to the results of a large Israeli study. The researchers used data on more than 2 million Israeli adolescents ages 16 to 19 years collected from 1967 to 2011 and linked it to cancer data from the Israel National Cancer Registry. They identified 4,021 cases of NHL. From there, they explored if excess BMI was linked with NHL diagnosis. The researchers conducted a multivariable analysis adjusting for sex, year of birth, and age at examination, and found that weight was positively associated with an NHL diagnosis. Participants who were overweight or obese had a 25% increased risk for NHL diagnosis (hazard ratio, 1.25; 95% CI, 1.13–1.37). Height in adolescence was also linked with an increased risk for NHL.
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FDA Approves Obinutuzumab for Follicular Lymphoma:
The FDA has approved obinutuzumab (Gazyva) in combination with bendamustine followed by monotherapy with obinutuzumab for treating follicular lymphoma patients who have relapsed after, or are refractory to, a rituximab-containing regimen. The study that led to the approval included 321 patients with follicular lymphoma randomized to either bendamustine with obinutuzumab (n = 155) or bendamustine alone (n = 166). On average, patients had received two prior therapies. Results of the study found that progression-free survival of patients treated with the combination was not reached vs 13.8 months in those treated with bendamustine alone (hazard ratio, 0.48; 95% CI, 0.34â0.68;
Read More. Image courtesy of Genentech.
FDA Approves Melphalan Formulation for Multiple Myeloma:
The US Food and Drug Administration (FDA) has approved Captisol-enabled melphalan (Evomela) for two indications in multiple myeloma-as a palliative treatment for multiple myeloma patients for whom oral therapy is not appropriate and for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation (HSCT). The trial that led to the approval was a multicenter, open-label, phase IIb study that included 61 patients. The overall response rate to the drug was 100%, with a complete response rate of 21%, according to an independent review. Melphalan is already used in the treatment of multiple myeloma, and is the primary drug in conditioning therapy prior to HSCT. The new formulation does not contain propylene glycol and is stable at room temperature for 4 hours in addition to the 1 hour following reconstitution.
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FDA Approves First Drug for Severe Hepatic VOD After HSCT:
The US Food and Drug Administration (FDA) has approved defibrotide sodium (Defitelio) for the treatment of hepatic veno-occlusive disease (VOD) following hematopoietic stem cell transplantation (HSCT) in both adults and children. This is the first drug approved for the life-threatening complication. The approval was based on data from 528 patients across three trials. All patients in the trials had a diagnosis of hepatic VOD with renal or pulmonary dysfunction following HSCT. In a phase II trial, 44% of patients survived to 100 days after HSCT. In a phase III trial, this rate was 38%, and in an expanded access cohort the 100-day survival rate was 45%. The FDA noted that the expected survival rates at 100 days after HSCT would be between 21% and 31% for patients who did not receive defibrotide.
. Image courtesy of Jazz Pharmaceuticals.
Late Recurrence a Concern for AML After ASCT:
Patients with acute myeloid leukemia (AML) who have undergone autologous stem cell transplantation (ASCT) and survived without disease recurrence for at least 2 years are still at risk for late recurrences, according to the results of a large retrospective study. The study included 3,567 adults with AML who underwent transplant during first or second complete remission from 1990 to 2008. The transplant source was bone marrow for 32% of patients and peripheral blood for 68% of patients. Among this group of patients, the probability of leukemia-free survival at 5 years was 86% and at 10 years it was 76%. At 5 years, the recurrence incidence was 11%, but by 10 years it had increased to 16%. Increasing patient age, peripheral blood grafts, and adverse French–American–British subtypes (including M0, M6, or M7) were all associated with an increased risk for recurrence.
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Upfront Transplant Best for Younger Multiple Myeloma Patients:
Undergoing upfront autologous stem cell transplantation (ASCT) is still the preferred treatment of choice for patients aged 65 or younger with newly diagnosed multiple myeloma, according to interim results of a phase III trial. Median progression-free survival was not yet reached. With a median follow-up of 2 years, results showed a 24% improvement in progression-free survival among patients assigned to high-dose melphalan and ASCT (hazard ratio [HR], 0.76; 95% CI, 0.61–0.84;
= .010). Improved progression-free survival was seen across multiple subgroups examined in the study. Specifically, patients with revised International Staging System stage III disease had a 48% improved progression-free survival with ASCT (HR, 0.52; 95% CI, 0.32–0.85;
= .01) and patients classified as having high-risk cytogenetics had a 28% improvement (HR, 0.72; 95% CI, 0.54–0.97;
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FDA Approves Nivolumab for Relapsed Classical Hodgkin Lymphoma:
The US Food and Drug Administration (FDA) granted accelerated approval of nivolumab (Opdivo) based on overall response rate in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. The FDA approved nivolumab based on a combined analysis of 95 patients who took part in the phase II CheckMate 205 and phase I CheckMate 039 trials. The patients studied, who were previously treated with autologous HSCT and brentuximab vedotin and had a median of five prior systemic regimens, received a median of 17 nivolumab doses. Of the 95 patients, 62 patients had an overall response (65%) with nivolumab; 7 patients (7%) achieved a complete response and 55 patients (58%) achieved a partial response. The median time to response was 2.1 months and the estimated median duration of response was 8.7 months.
. Image courtesy of Bristol-Myers Squibb.
All Oral Ixazomib Combo Effective for Newly Diagnosed Myeloma:
A phase I/II study testing the all oral combination of ixazomib, cyclophosphamide, and dexamethasone showed that patients with newly diagnosed multiple myeloma responded well to the experimental treatment regimen. Phase I of the study was designed to find the maximum tolerated dose. In phase II of the trial the researchers determined the rate of complete plus very good partial response. With a median follow-up of 13.4 months, 17 patients remained on treatment with a median of 7 cycles administered. The main reason for discontinuation was alternative treatment options, which was often autologous stem cell transplant. The overall response rate for the 48 evaluable patients in the two parts of the trial was 77%, with a very good partial response or better in 35% of patients. The median duration of response in the phase II study was 18.4 months.
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Systemic Therapy for Lymphoma Appears Safe After First Trimester:
A retrospective study looking at a small number of women diagnosed with and treated for Hodgkin or non-Hodgkin lymphoma while pregnant has found that systemic therapy given after the first trimester was safe and resulted in acceptable maternal and fetal outcomes. The researchers looked at 39 pregnant women (median age, 28 years) diagnosed with lymphoma at a single center from 1991 to 2014. The majority (82%) had stage I or II disease. Of the 39 women, 24 received antenatal therapy and 12 chose to defer their treatment until after delivery. Four of the 24 women undergoing antenatal therapy experienced miscarriage, two of which occurred in the first trimester. With a median follow-up of 67.9 months there was a 5-year progression-free survival of 74.7% and overall survival of 82.4%. No differences in terms of survival were seen for women who underwent antenatal compared with postnatal treatment.
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Anthracycline-Based Therapy Best for Elderly DLBCL Patients:
Results of a single-center analysis indicated that patients aged 80 or older with diffuse large B-cell lymphoma (DLBCL) had superior outcomes with anthracycline-based therapies, reinforcing data found in previous clinical studies. The researchers examined information on 207 patients aged 80 or older diagnosed with DLBCL from 2002 to 2014. More than one-half of patients had intermediate- to high-risk or high-risk International Prognostic Index scores. Patients received frontline treatment with the anthracycline-based regimens R-CHOP (70%) and R-EPOCH (6%); and 10% received the non-anthracycline–based regimens R-CEOP or R-CVP. In comparing outcomes by treatment group, the researchers found that the 3-year failure-free survival rates were better for patients who received R-CHOP (63%) and R-EPOCH (74%) compared with R-CEOP or R-CVP (23%). Three-year overall survival rates were also higher in patients who received R-CHOP (62%) or R-EPOCH (73%) compared with the non-anthracycline–based regimens (25%).
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Nilotinib, Dasatinib Offer Similar Outcomes in CML Patients:
A propensity score–matched comparison of two phase II trials found that the tyrosine kinase inhibitors dasatinib and nilotinib offer similar responses and outcomes as first-line therapy for patients with chronic-phase chronic myeloid leukemia (CML). Treatment responses were similar between the groups. The study included 102 dasatinib and 104 nilotinib patients with newly diagnosed CML, and 87 of each of those were analyzed after propensity matching was complete. The 3-month
ratio < 10% rate was 93% with dasatinib and 94% with nilotinib (
= .25). The rates of major molecular response at 12 months were 77% and 85%, respectively (
= .13). The molecular response with 4.5-log reduction in the ratio at 36 months was 66% in the dasatinib group and 64% in the nilotinib group (
= .96). The overall survival rate at 3 years was 99% with dasatinib and 93% with nilotinib (
= .95). Other survival endpoints were also similar.
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CLL Patients Responded to Influenza Vaccine:
Patients with chronic lymphocytic leukemia (CLL) taking ibrutinib showed an antibody response to the influenza vaccine, according to a data from a small study. According to the letter, patients with CLL have immune dysfunction, with infections accounting for as many as 60% of deaths in these patients. To try to combat these infections, influenza vaccinations are recommended; however, it was unknown whether patients with CLL taking ibrutinib could mount an immune response to vaccination. Nineteen patients received one dose of the vaccine (containing A/California/7/2009, A/Texas/50/2012, and B/Massachusetts/2/2012 viruses). The researchers measured hemagglutinin inhibition antibody titers at baseline and 3 months after vaccination. More than one-quarter (26%) of patients had seroconversion for at least one strain (95% CI, 9.2%–51.2%). Seroconversion for the California strain occurred in three patients (16%), the Texas strain in five patients (26%), and the Massachusetts strain in two patients (11%).
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Pregnancy Screening Before Chemotherapy Unlikely in Young ALL Patients:
Many adolescent girls with leukemia did not receive pregnancy screening before undergoing teratogenic exposure, according to the results of a study that included over 1,000 patients with either acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Pregnancy screening rates were compared with adolescents girls admitted to the emergency room (ER). Appropriately timed pregnancy screens were conducted in 35% of patients with ALL, 64% of patients with AML, and 58% of ER patients. Patients with ALL were 30% less likely to have a pregnancy test compared with ER patients (adjusted prevalence ratio, 0.71; 95% CI, 0.65–0.78). No significant difference was found between patients with AML and ER patients. Although increasing age was associated with increased pregnancy screening, the researchers noted that patient age did not seem to explain the higher rate of screening in patients with AML compared with the ER patients.
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Cost of TKIs May Be Deterrent in CML Patients on Medicare:
An analysis of tyrosine kinase inhibitor (TKI) initiation and adherence in Medicare beneficiaries with chronic myeloid leukemia (CML) suggests that out-of-pocket costs may be a barrier to treatment. Only two-thirds of patients started TKI therapy within 180 days of diagnosis. The price of 1 year of TKI therapy ranged from about $9,000 to $10,000. The researchers studied 393 individuals (mean age, 77 years) diagnosed with CML between 2007 and 2011. More than 40% of patients were older than 80. In total, 68.2% of patients initiated TKI therapy within 180 days after diagnosis. The median time to TKI initiation among initiators was 75 days, and receipt of cost-sharing subsidies was associated with earlier initiation (hazard ratio, 1.35). Age older than 80 years compared with younger than 70 was significantly associated with a reduced likelihood of adherence (adjusted risk ratio, 0.74).
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Chronic Hepatitis B, C Linked With Non-Hodgkin Lymphoma in HIV Patients:
Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) was associated with an increased risk for non-Hodgkin lymphoma among patients with HIV who are on antiretroviral therapy, according to the results of a study that looked at data from 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). The researchers looked for patients with HIV and information on HBV surface antigen measurement and detectable HCV RNA, or a positive HCV antibody test. Infection with HBV and HCV was associated with an increased risk for non-Hodgkin lymphoma. Among treatment-naive patients, the hazard ratio (HR) for non-Hodgkin lymphoma with HBV was 1.33 (95% CI, 0.69–2.56) and with HCV was 0.67 (95% CI, 0.40–1.12). Among treated patients, the HR with HBV was 1.74 (95% CI, 1.08–2.82) and with HCV was 1.73 (95% CI, 1.21–2.46).
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