Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial
Mené sur 38 patients atteints d'une leucémie lymphoïde aiguë Ph- récemment diagnostiquée (âge médian : 37 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans récidive, et la toxicité d'un traitement de première ligne combinant chimiothérapie intensive (de type hyper-CVAD) et blinatumomab dispensé de façon séquentielle
Background : Blinatumomab is effective in relapsed or refractory B-cell acute lymphocytic leukaemiaand results in high rates of minimal residual disease negativity. We aimed to establishwhether the incorporation of blinatumomab into front-line therapy for acute lymphocyticleukaemia could improve outcomes.
Methods : We conducted a single-arm, phase 2 trial at The University of Texas MD Anderson CancerCenter (Houston, TX, USA). Patients aged 14 years or older with confirmed, newly diagnosedPhiladelphia chromosome (Ph)-negative B-cell acute lymphocytic leukaemia were eligible,including patients who had received up to one course of chemotherapy before enrolment.Patients received four cycles of intensive chemotherapy (hyper-CVAD [hyperfractionatedcyclophosphamide, vincristine, doxorubicin, and dexamethasone] alternating with high-dosemethotrexate and cytarabine), followed by four cycles of blinatumomab consolidation(up to 28
μg/day by continuous intravenous infusion for 28 days, given every 42 days).Maintenance consisted of 15 cycles of alternating blocks of three cycles of POMP (6-mercaptopurine,vincristine, methotrexate, and prednisone) chemotherapy and one of blinatumomab. Theprimary endpoint was relapse-free survival evaluated in the intention-to-treat population.The trial is registered with ClinicalTrials.gov, NCT02877303, and is still enrolling patients.
Findings
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Between Nov 14, 2016, and Aug 27, 2020, 38 patients with newly diagnosed B-cell acutelymphocytic leukaemia were treated (median age 37 years [IQR 29
–45]; 26 [68%] male;21 [55%] White, non-Hispanic). With a median follow-up of 37 months (IQR 28–49), estimated3-year relapse-free survival was 73% (95% CI 56–85). No patients relapsed more than2 years after the start of therapy. One (3%) patient developed transient grade 3 cytokinerelease syndrome, and four (11%) patients had a grade 3 blinatumomab-related neurologicalevent. The most common non-haematological grade 3–4 adverse events were infections,which occurred in 14 (37%) of 38 patients during induction and in 27 (71%) of 38 patientsduring consolidation chemotherapy cycles. One (3%) patient discontinued therapy becauseof treatment-related neurotoxicity. There were two deaths—one due to infection andone due to respiratory failure—which were not considered treatment-related.
Interpretation : Front-line sequential chemotherapy with blinatumomab resulted in encouraging long-termsurvival. Future randomised studies should evaluate the routine incorporation of blinatumomabin the treatment of patients with Ph-negative B-cell acute lymphocytic leukaemia.
The Lancet Haematology , résumé, 2021