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Blinatumomab shows promise for subset of relapsed, refractory ALL
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Single-agent blinatumomab demonstrated activity in high-risk patients with Philadelphia chromosome–positive B-cell precursor acute lymphoblastic leukemia, according to results of a phase 2 clinical trial.
“These data demonstrate efficacy of single-agent blinatumomab in relapsed/refractory Philadelphia chromosome–positive [Ph+] ALL, suggesting a possible future role in Ph–like ALL and combination therapies with tyrosine kinase inhibitors for this disease setting,” Giovanni Martinelli, MD, from the Institute of Hematology and Medical Oncology in Bologna, Italy, and colleagues wrote.
Previous data confirmed antileukemia activity of blinatumomab (Blincyto, Amgen) in patients with Philadelphia chromosome–negative B-cell precursor ALL; however, these patients often have different baseline demographics than patients with Ph+ALL, which may impact outcomes.
Therefore, Martinelli and colleagues conducted a multi-institutional trial to determine efficacy and safety of blinatumomab — a bispecific T-cell engager antibody construct designed to direct cytotoxic T cells to CD19–expressing B cells — among patients with PH+ B-cell precursor ALL.
Patients had relapsed after or were refractory to at least one second-generation or later tyrosine kinase inhibitor, or were intolerable to second-generation or later TKIs and refractory to imatinib. Forty-four percent of patients previously relapsed after allogeneic hematopoietic stem cell transplantation.
Forty-five patients (median age, 55 years; range, 23-78) received continuous IV infusion of 9 µg blinatumomab per day in week 1 of cycle 1, followed by 28 mg per day in 28-day cycles. The median number of cycles was two (range, 1-5).
Complete remission or complete remission with partial hematologic recovery within the first two cycles of treatment served as the primary endpoint.
Among the patients, 16 (36%; 95% CI, 22-51) achieved a complete remission (n = 14) or complete remission with partial hematologic recovery (n = 2) during the first two cycles. Eighty-eight percent of these patients also achieved a complete minimal residual disease (MRD) response.
Patients achieved responses to blinatumomab therapy regardless of prior TKI therapy.
Seven of the responding patients underwent allogeneic HSCT, including four who remained in continuous blinatumomab-induced remission.
Four of the ten patients who harbored a T315I mutation responded to the treatment.
Over a median follow-up of 9 months, median RFS was 6.7 months (95% CI, 4.4-not estimable) overall and 6.8 months (95% CI, 4.4-not estimable) among the 14 patients who achieved complete MRD response.
The median OS was 7.1 months (95% CI, 5.6-not estimable).
The researchers noted the safety profile was consistent with previous data from patients with Ph–negative B-cell precursor ALL. The most commonly observed adverse events were pyrexia (58%), febrile neutropenia (40%) and headache (31%). Three patients had grade 1 or grade 2 cytokine release syndrome.
Three patients experienced grade 3 neurologic events, one of which required temporary treatment interruption. No grade 4 or worse neurologic events were observed. – by Melinda Stevens
Disclosures: Martinelli reports consultant/advisory roles with ARIAD Pharmaceuticals, Celgene, Pfizer and Roche, and speaker roles with Bristol-Myers Squibb and Novartis. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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