ASH Clinical News July 2017 V2 - Page 24

Literature Scan New and noteworthy research from the medical literature landscape Blinatumomab Versus Standard-of-Care Chemotherapy in Acute Lymphocytic Leukemia In a multinational, prospective, ran- domized, phase III study, investigators found that the anti-CD19/CD3 bispe- cific T-cell engager antibody blinatu- momab improved survival outcomes, compared with standard-of-care che- motherapy, for patients with relapsed/ refractory, B-cell precursor acute lymphocytic leukemia (ALL). Treatment with blinatumomab also led to longer event-free survival (EFS) and appeared to lower adjusted rates of serious adverse events (AEs), according to an article in the New England Journal of Medicine led by Hagop Kantarjian, MD, chair of the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston, and co-authors. “Most adults with B-cell precur- sor ALL will relapse and will die from complications of resistant disease or as- sociated treatment,” Dr. Kantarjian and co-authors explained, adding that “more effective treatment is needed” for this patient population. Patients were enrolled between January 2014 and September 2015. The trial included 405 adult patients with relapsed/refractory, B-cell precursor ALL that was: refractory to primary induc- tion therapy or to salvage with intensive combination chemotherapy; in first relapse with the first remission lasting <12 months; in second or greater relapse; or in relapse at any time after alloge- neic hematopoietic cell transplantation (alloHCT). Other criteria included >5 percent bone marrow (BM) blasts and an Eastern Cooperative Oncology Group performance status score of ≤2. Patients were excluded from the trial if they had other active cancers, had grade ≥2 acute graft-versus-host disease (GVHD) or chronic GVHD, or had received HCT or other active anti-cancer treatment within 4 to 12 weeks prior to randomization. TABLE 1. Patients were randomized 2:1 to receive one of the following: • blinatumomab administered in 6-week cycles consisting of 4 weeks of treatment (9 μg/day during week 1 of induction and 28 μg/day thereafter) and 2 weeks of no treat- ment (n=271; mean age = 40.8±17.1 years; range = 18-80 years) • investigator’s choice of chemotherapy (n=134; mean age = 41.1±17.3 years; range = 18-78 years), including: o fludarabine, high-dose cytosine arabinoside, and granulocyte colony-stimulating factor with or without anthracycline (45%; n=49) o a high-dose cytosine arabinoside- based regimen (17%; n=19) o a high-dose methotrexate-based regimen (20%; n=22) o a clofarabine-based regimen (17%; n=19) Protocol-specified therapy could be discontinued at any time after the first treatment cycle and the patient could subsequently undergo HCT if the in- vestigator determined that such actions were in the patient’s best interest. Patients in morphologic remission (≤5% BM blasts) also received up to three cycles of consolidation therapy, and those who were in continued morphologic remission received up to 12 months of maintenance therapy. In the blinatumomab group, maintenance therapy consisted of a 4-week continu- ous infusion every 12 weeks, and all patients received dexamethasone prior to blinatumomab dosing to prevent infusion reactions. Most patients (n=376) received at least one treatment dose. At data cutoff (January 4, 2016), 22 patients (8%) in the blinatumomab cohort and zero in the chemotherapy group were still on treatment. The median number of treat- ment cycles was two (range = 1-9 cycles) for those in the blinatumomab cohort and one (range = 1-4 cycles) in the che- motherapy cohort. A total of 251 deaths were reported. Investigators found that overall survival (OS; primary endpoint) was significantly longer with blinatumomab (median OS = 7.7 vs. 4.0 months; hazard ratio [HR] = 0.71; 95% CI 0.55-0.93; p=0.01). EFS was also longer for patients re- ceiving blinatumomab versus chemother- apy (6-month estimate = 31% vs. 12%; HR=0.55; 95% CI 0.43-0.71; p<0.001), as was the median duration of remission (7.3 vs. 4.6 months; p values not report- ed). And remission rates (see TABLE 1 ). “Patients in the blinatumomab group who achieved complete remission with full, partial, or incomplete hematologic recovery had a higher incidence of re- sponse with respect to minimal residual disease (MRD) than did patients in the chemotherapy group, which highlighted the depth and quality of remissions achieved with blinatumomab,” the au- thors noted. Twenty-four percent of patients in both the blinatumomab and chemo- therapy groups proceeded to alloHCT, which is “a major goal in this popula- tion,” the authors noted. “AEs that occurred in the blina- tumomab group were consistent with those reported in previous tri- als,” the authors noted. Serious AEs were reported more frequently in the REFERENCE Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836-47. Best Hematologic Response Within 12 Weeks After Treatment Initiation Blinatumomab (n=271) Chemotherapy (n=134) Treatment Difference (%) p Value Complete remission with full hematologic recovery 91; 33.6% (95% CI 28.0-39.5) 21; 15.7% (95% CI 10.0-23.0) 17.9 (95% CI 9.6-26.2) <0.001 Complete remission with full, partial, or incomplete hematologic recovery 119; 43.9% (95% CI 37.9-50.0) 33; 24.6% (95% CI 17.6-32.8) 19.3 (95% CI 9.9-28.7) <0.001 Complete remission with partial hematologic recovery 24; 8.9% (95% CI 5.8-12.9) 6; 4.5% (95% CI 1.7-9.5) − − Complete remission with incomplete hematologic recovery 4; 1.5% (95% CI 0.4-3.7) 6; 4