TY - JOUR
T1 - Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia
T2 - a single-arm, single-centre, phase 2 trial
AU - Jabbour, Elias
AU - Short, Nicholas J.
AU - Jain, Nitin
AU - Thompson, Philip A.
AU - Kadia, Tapan M.
AU - Ferrajoli, Alessandra
AU - Huang, Xuelin
AU - Yilmaz, Musa
AU - Alvarado, Yesid
AU - Patel, Keyur P.
AU - Garcia-Manero, Guillermo
AU - Macaron, Walid
AU - Garris, Rebecca
AU - Konopleva, Marina
AU - Ravandi, Farhad
AU - Kantarjian, Hagop
N1 - Funding Information:
Amgen provided funding for a research nurse and free blinatumomab for the study.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/12
Y1 - 2022/12
N2 - Background: Blinatumomab is effective in relapsed or refractory B-cell acute lymphocytic leukaemia and results in high rates of minimal residual disease negativity. We aimed to establish whether the incorporation of blinatumomab into front-line therapy for acute lymphocytic leukaemia could improve outcomes. Methods: We conducted a single-arm, phase 2 trial at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 14 years or older with confirmed, newly diagnosed Philadelphia 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 [hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone] alternating with high-dose methotrexate 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. The primary 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: Between Nov 14, 2016, and Aug 27, 2020, 38 patients with newly diagnosed B-cell acute lymphocytic 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), estimated 3-year relapse-free survival was 73% (95% CI 56–85). No patients relapsed more than 2 years after the start of therapy. One (3%) patient developed transient grade 3 cytokine release syndrome, and four (11%) patients had a grade 3 blinatumomab-related neurological event. 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 patients during consolidation chemotherapy cycles. One (3%) patient discontinued therapy because of treatment-related neurotoxicity. There were two deaths—one due to infection and one due to respiratory failure—which were not considered treatment-related. Interpretation: Front-line sequential chemotherapy with blinatumomab resulted in encouraging long-term survival. Future randomised studies should evaluate the routine incorporation of blinatumomab in the treatment of patients with Ph-negative B-cell acute lymphocytic leukaemia. Funding: Amgen.
AB - Background: Blinatumomab is effective in relapsed or refractory B-cell acute lymphocytic leukaemia and results in high rates of minimal residual disease negativity. We aimed to establish whether the incorporation of blinatumomab into front-line therapy for acute lymphocytic leukaemia could improve outcomes. Methods: We conducted a single-arm, phase 2 trial at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 14 years or older with confirmed, newly diagnosed Philadelphia 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 [hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone] alternating with high-dose methotrexate 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. The primary 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: Between Nov 14, 2016, and Aug 27, 2020, 38 patients with newly diagnosed B-cell acute lymphocytic 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), estimated 3-year relapse-free survival was 73% (95% CI 56–85). No patients relapsed more than 2 years after the start of therapy. One (3%) patient developed transient grade 3 cytokine release syndrome, and four (11%) patients had a grade 3 blinatumomab-related neurological event. 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 patients during consolidation chemotherapy cycles. One (3%) patient discontinued therapy because of treatment-related neurotoxicity. There were two deaths—one due to infection and one due to respiratory failure—which were not considered treatment-related. Interpretation: Front-line sequential chemotherapy with blinatumomab resulted in encouraging long-term survival. Future randomised studies should evaluate the routine incorporation of blinatumomab in the treatment of patients with Ph-negative B-cell acute lymphocytic leukaemia. Funding: Amgen.
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UR - http://www.scopus.com/inward/citedby.url?scp=85142828619&partnerID=8YFLogxK
U2 - 10.1016/S2352-3026(22)00285-X
DO - 10.1016/S2352-3026(22)00285-X
M3 - Article
C2 - 36279879
AN - SCOPUS:85142828619
SN - 2352-3026
VL - 9
SP - e878-e885
JO - The Lancet Haematology
JF - The Lancet Haematology
IS - 12
ER -