Top Hematologic Cancer News of 2017

No Association Between Response Rates and Survival in Newly Diagnosed Multiple Myeloma: Results of a recent meta-regression analysis of 63 randomized clinical trials out of Greece concluded that there was no association between conventional response outcomes, such as complete response (CR) or very good partial response (VGPR), and overall (OS) or progression-free survival (PFS) in patients with newly diagnosed multiple myeloma in populations of patients who received stem cell transplant and those who did not. Due to current conflicting data on the role of achieving CR and OS and PFS, researchers note that given the results of newer trials which suggest that minimal residual disease (MRD) status may be a replacement for outcomes in myeloma patients with CR, that prospective studies should include MRD in addition to conventional response outcomes to be sure that newly diagnosed patients survival rates are accurately reported. Read more. Image © Jarun Ontakrai/shutterstock.com

Low-Dose ATLG Prevents GVHD in Pediatric Hematologic Malignancies: A newly published randomized phase III study of pediatric patients showed lower doses of rabbit anti–T-lymphocyte globulin (ATLG) was superior to a higher dose in children with hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation from an unrelated donor. Study results report that after a median 3.4-year follow-up, the 100-day cumulative incidence rate of grade II to IV acute graft-versus-host disease was 36% for the 15-mg/kg group vs. 29% for the 30-mg/kg group; cumulative incidence rate of nonrelapse mortality was 9% for patients assigned to the 15-mg/kg dose vs. 19% in the 30-mg/kg group. Cumulative incidence rate of disease recurrence was 14% in the 15-mg/kg group and 20% in the 30-mg/kg group. Additionally, the 15-mg/kg group had a significantly improved 5-year event-free survival rate (77% vs. 61%; P = .028). Researchers conclude that this patient population should receive 15-mg/kg ATLG dose as the standard serotherapy regimen. Read more. Image © Komsan Loonprom/shutterstock.com

Smoking Worsens Prognosis for Patients With CML: The results of the German CML Study IV report a link between mortality and disease progression in patients with chronic myeloid leukemia (CML) who are smokers. Of the 1,536 patients evaluated, 20% of the 1,326 patients with a smoking status available for analysis were determined to be smokers. Researchers note an 87% 8-year survival rate for those who were nonsmokers compared with smokers who experienced an 83% 8-year survival rate with a mortality hazard ratio of 2.08 (95% CI, 1.4–3.1; P < .001); however, the effects of smoking were also based on advancing age and other comorbidities. Smokers additionally experienced a higher rate of disease progression over an 8-year cumulative incidence rate, with a rate of 12% in smokers vs. 7% in nonsmokers. Smoking cessation in those with CML, specifically those over age 60 should be encouraged and supported. Read more. Image © Wern Images/shutterstock.com

Final Results of Landmark Imatinib Study in CML Show Long-Term Benefit: Results of the IRIS study revealed that imatinib shows persistent efficacy over time without unacceptable late toxic or cumulative effects. The randomized trial enrolled 1,106 study participants and yielded a 76.2% 18-month response rate in patients treated with imatinib vs. 14.5% in those treated with interferon-alfa plus cytarabine. This landmark discovery led to researchers crossing participants over to the interferon-alfa plus cytarabine arm to the imatinib arm. Final analysis of results was on the imatinib arm of the trial. The 10-year survival rate in subjects receiving first-line treatment with imatinib ranged from 64.4% to 84.4%. Despite a high number of participants being crossed over to the imatinib arm with direct survival comparisons being precluded, a hazard ratio of 0.74 (95% CI, 0.56–0.99; P = .04) for mortality in favor of imatinib was calculated. Cumulative major cytogenic response to imatinib was 89%; complete response was experienced in 82.8% of participants. Read more. Image © S_L/shutterstock.com

Escalated BEACOPP Plus Rituximab in Advanced Hodgkin Lymphoma Fails to Improve Outcomes: The results of the phase III HD18 trial by the German Hodgkin Study Group determined that the addition of rituximab to an escalated regimen of BEACOPP did not improve progression-free survival (PFS) in patients with advanced-stage Hodgkin lymphoma. The study additionally determined that the use of a PET scan following the second cycle of BEACOPP did not identify patients who are at high risk for treatment failure. During the study, patients who were PET-2 positive were randomized to six additional courses of BEACOPP escalated with or without rituximab. Results of the study reported at 3-year PFS with 91.4% in the BEACOPP escalated arm vs. the rituximab arm who experienced a 93% PFS. Read more. Image © Molekuul_be/shutterstock.com

Ponatinib Extends Survival Over Transplant in Chronic Phase CML: The results of a new study that included patients from the PACE trial and the European Bone Marrow Transplant registry revealed that treatment with ponatinib yielded better overall survival (OS) compared with allogeneic stem cell transplantation (allo-SCT) in patients with chronic phase chronic myeloid leukemia (CP-CML) with a T315I mutation. Ponatinib was not found to show better or worse outcomes in in blast-crisis phase (BC)-CML, or in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). In those with CP-CML who received ponatinib vs. those who underwent allo-SCT, the 24- and 48-month OS rates were 84% vs. 60.5% and 72.7% vs. 55.8% respectively. The median OS rate in allo-SCT patients was 103.3 months; however, the OS was not reached with ponatinib. Read more. Image © fizkes/shutterstock.com

Hodgkin Lymphoma Survivors at High Risk for Second Cancers: The results of a new study report that Hodgkin lymphoma survivors experience 2.39-fold increased secondary cancer risk, with the highest risk among those with a family history of specific cancers. This risk was present as far as 30 years following disease treatment. Data collected from the Swedish Family-Cancer Project Database showed that nearly 30% of the evaluated patients had one or more first-degree relatives with cancer, and were in turn 2.8 times more likely to develop a secondary cancer vs. those without relation to a first-degree relative with cancer (2.2-fold increase). Hodgkin lymphoma survivors with a first-degree relative with cancer had a 1.3-fold increased risk for all cancers, a 3.3-fold increase in lung cancer, 2.1-fold increase in colorectal cancer, and a 1.8-fold increased risk for secondary breast cancer. Women diagnosed younger than 35 experienced a 13.8% risk of breast cancer vs. 3% in those over 35 at diagnosis. Read more. Image © create jobs 51/shutterstock.com

Fifth Course of Chemotherapy Benefited Pediatric Low-Risk AML Patients: Results of the pooled analysis of two Children’s Oncology Group (COG) trials were presented by Dr. Kelly Getz at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. Dr. Getz discussed that the removal of a fifth course of chemotherapy containing cytarabine resulted in worse overall survival (OS) and disease-free survival in pediatric patients with low-risk acute myeloid leukemia (AML) per the results of the AAML 1031 trial and the AAML 0531 trials. Five course treatment OS reached 87.5% vs. 80.6% with four course treatment and disease-free survival rates of 69.9% and 59%, respectively. Those with uninformative cytogenetic or molecular markers with negative minimal residual disease at the end of induction were noted to experience the most benefit (nearly 2-fold benefit from receiving a fifth dose of chemotherapy) vs. those with favorable cytogenetic and molecular features who did not experience benefit from receiving a fifth dose of therapy. Read more. Image © Chaikom/shutterstock.com

High-Dose Chemotherapy Plus Transplant Not Recommended for DLBCL: The results of an Italian study report that treatment of high-risk diffuse large B-cell lymphoma (DLBCL) with abbreviated course of rituximab dose-dense chemotherapy plus high-dose cytarabine, mitoxantrone, and dexamethasone (R-MAD) plus carmustine, etoposide, cytarabine, and melphalan (BEAM) plus autologous stem cell transplantation compared with a full course of rituximab dose-dense chemotherapy did not improve overall survival. Based on the results of this study the standard treatment for DLBCL with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) should be given as standard treatment. Results of the randomized trial reported that although the 2-year failure-free survival rates with transplant were higher (71% vs. 62%), overall survival was not significantly changed in 5-year overall survival rates between the groups of participants who underwent transplant. Read more. Image © CI Photos/shutterstock.com

Daratumumab/Pomalidomide Combo Approved for Relapsed, Refractory Myeloma: Based on the findings of the phase I EQUULEUS study, the FDA approved the combination of daratumumab (Darzalex) with pomalidomide (Pomalyst) and dexamethasone for the treatment of relapsed or refractory multiple myeloma. Eligible patients must have had at least two prior therapies including lenalidomide and a proteasome inhibitor to receive daratumumab. Findings of the EQUULEUS study revealed a 59% overall response rate in study participants treated with the drug combination. Of these, 8% achieved stringent complete response, 6% achieved complete response, and 28% achieved a very good partial response. The study reported a median time to response to treatment of 1 month, with the duration of treatment 13.6 months. Commonly reported adverse reactions included infusion reaction, diarrhea, nausea, vomiting, fatigue, pyrexia, upper respiratory tract infection, muscle spasm, cough, and dyspnea. Serious adverse reactions were reported in approximately half of the study participants. Read more.

FDA Clears Test to Help Diagnose, Identify Blood Cancer Type: The FDA has approved ClearLLab Reagents (T1, T2, B1, B2, M) for the detection of hematologic malignancies such as acute and chronic leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and non-Hodgkin lymphoma. With the use of fluorescent dyes which mark the cell’s surface proteins for flow cytometry evaluation, ClearLLab Reagents (T1, T2, B1, B2, M) is able to detect cancer cells found in the blood, bone marrow, and lymph nodes. The FDA approval comes after the release of a recent multi-site study that reported that in 93.4% of cases the test was able to align with the study site’s final diagnosis and additionally was able to detect cancer 84.2% of the time. Read more. Image © Romaset/shutterstock.com

FDA Warns of Safety Concerns for Pembrolizumab Combinations in Myeloma: Three clinical trials were placed on hold by the US Food and Drug Administration (FDA) due to concerns for pembrolizumab combinations in myeloma. The KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023 trials evaluating the programmed death 1 (PD-1) inhibitor pembrolizumab in combination with pomalidomide or lenalidomide for patients with multiple myeloma were placed on hold due to the increase in deaths on the pembrolizumab arms of KEYNOTE-183 and KEYNOTE-185 trials. These results are indicative that that the risks of treatment with the investigational drug plus pomalidomide or lenalidomide outweighed any potential benefit. These safety concerns are being evaluated by the FDA with pembrolizumab’s manufacturer, Merck. Read more.

CRP Levels Before Transplant Linked With Survival in Multiple Myeloma: According to a new study, patients with an elevation in C-reactive protein (CRP) prior to an autologous stem cell transplantation (ASCT) for multiple myeloma experienced a worse overall survival (OS) rate. This was noted to be more common in those who underwent a transplant 12 months following diagnosis. Of the 1,111 patients evaluated with newly diagnosed or relapsed/refractory myeloma who underwent transplant at the Mayo Clinic from 2007 to 2015, 76% underwent early transplantation defined as 12 months or less from diagnosis; those who had an elevation in CRP were noted to experience a worse OS as opposed to those with a normal CRP (91 months vs. not reached; P = .011). Additionally, those who underwent delayed transplant with an elevation in CRP also experienced a worse OS rate as compared with those who had normal CRP levels (30 months vs. 73 months; P < .001). Read more. Image © CI Photos/shutterstock.com

FDA Approves Maintenance Lenalidomide for Multiple Myeloma: Lenalidomide (Revlimid) received expanded FDA approval for use as maintenance therapy for patients with multiple myeloma following autologous stem cell transplant (ASCT). Clinical trial results from CALGB 100104 and IFM 2005-02 showed that lenalidomide maintenance therapy increased progression-free survival (PFS) in patients following ASCT. Results of the CALGB 100104 trial yielded a median PFS of 5.7 years vs. 1.9 years with placebo. IFM 2005-02 yielded a median PFS of 3.9 years vs. 2 years with placebo when lenalidomide was given as maintenance therapy. Neither study evaluated overall survival rates. Commonly experienced adverse events included thrombocytopenia, leukopenia, neutropenia, anemia, diarrhea, gastroenteritis, bronchitis, nasopharyngitis, upper respiratory tract infection, cough, rash, asthenia, muscle spasm, pyrexia, and fatigue. Risk of secondary cancers increased to 14.9% vs. 8.8% in those receiving lenalidomide vs. placebo, including nonmelanoma skin cancers (3.9% vs 2.6%). Read more. Image © Molekuul_be/shutterstock.com