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Improved EFS With Blinatumomab vs Chemo for High-Risk First Relapse of BCP-ALL
Study findings being presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition suggest blinatumomab monotherapy as a new standard-of-care consolidation therapy before allogeneic hematopoietic stem cell transplant (alloHSCT) in young patients with high-risk first-relapse B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
“Children with high-risk first-relapse [BCP-ALL] are candidates for [alloHSCT] when a second complete morphological remission (CR2, M1 marrow) is achieved. Immuno-oncotherapy with blinatumomab…is efficacious in children with relapsed/refractory BCP-ALL,” wrote Franco Locatelli, MD, PhD, Department of Pediatric Hematology/Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, and colleagues.
Between November 2015 and to July 2019, a total of 108 patients with M1 (<5% blasts) or M2 (<25% and ≥5% blasts) marrow were enrolled in the phase 3, open-label, controlled trial by Dr Locatelli et al. The purpose of the study was to compare blinatumomab with high-risk consolidation (HC) 3 chemotherapy as pretransplant consolidation therapy for children with high-risk first-relapse BCP-ALL.
These patients were randomized in a 1:1 ratio after induction therapy and cycles of HC1 and HC2 chemotherapyto receive a third consolidation course with blinatumomab 15 µg/m2 daily for 4 weeks (n = 54) or HC3 (dexamethasone, vincristine, daunorubicin, methotrexate, ifosfamide, PEG-asparaginase; n = 54).
Of note, baseline characteristics were similar between the 2 treatment groups, with most patients having completed treatment (blinatumomab, 91%; HC3, 89%), and patients were given intrathecal chemotherapy with methotrexate, cytarabine, and prednisolone before treatment.
The main end point of the study was event-free survival (EFS; from randomization until date of relapse or M2 marrow after a CR; failure to achieve CR at the end of therapy; second malignancy; or death from any cause). The secondary end points included overall survival (OS), cumulative incidence of relapse, minimal residual disease (MRD) status, and adverse events (AEs).
Among those given blinatumomab and HC3, events were reported for 18 (33.3%) and 31 (57.4%) patients (median EFS, not reached vs 7.4 months, respectively). Blinatumomab was shown to reduce the risk for relapse by 64% compared with HC3 (hazard ratio [HR], 0.36; 95% CI, 0.19-0.66; P <.001). Furthermore, OS favored blinatumomab (HR, 0.43; 95% CI, 0.18-1.01).
The investigators observed MRD remission (MRD <10-4) in 43 (93.5%) of 46 patients given blinatumomab and 25 (54.3%) of 46 patients given HC3. Grade ≥3 treatment-emergent AEs were reported for 30 (57%) of 53 patients and 41 (80%) of 51 patients, respectively.
“As expected, grade ≥3 neurologic events occurred more frequently with blinatumomab than with HC3; no grade ≥3 cytokine release syndrome events were reported. Types of alloHSCT conditioning regimens received by patients as well as types of donors were balanced between groups,” Dr Locatelli and colleagues wrote.
“Blinatumomab monotherapy as consolidation therapy before alloHSCT in children with high-risk first-relapse BCP-ALL leads to significantly better EFS, lower risk of recurrence, and fewer grade ≥ 3 treatment-emergent AEs vs HC3, suggesting a new standard-of-care treatment for these patients,” they concluded.—Hina Porcelli
Locatelli F, Zugmaier G, Rizzari C, et al. Superior Event-Free Survival with Blinatumomab Versus Chemotherapy in Children with High-Risk First Relapse of B-Cell Precursor Acute Lymphoblastic Leukemia: A Randomized, Controlled Phase 3 Trial. Presented at: the 62nd ASH Annual Meeting and Exposition; December 5-8, 2021; virtual. Abstract 268.
