(ChemotherapyAdvisor) – Patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL) experience complete remission with blinatumomab, according to a team of German researchers. This conclusion is based on an abstract entitled “Anti-CD19 BiTE Blinatumomab Induces High Complete Remission Rate and Prolongs Overall Survival in Adult Patients with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL),” which was presented at the 17th Annual Congress of the European Hematological Association in Amsterdam, The Netherlands.
Relapsed/refractory B-precursor ALL in adults has a dismal prognosis, where only 35 to 40% of patients reach a hematological complete remission (CR) with a median overall survival of approximately 4.5 months, noted lead author Max D. Topp, MD, Würzburg University Hospital, Würzburg, Germany. The investigators conducted an exploratory Phase 2 trial in this patient cohort with blinatumomab, a bispecific T-cell engaging (BiTE) antibody that directs cytotoxic T-cells to CD19 expressing target cells.
Patients received blinatumomab by continuous intravenous infusion (28-day cycles, followed by one 14-day treatment-free interval). If the patients responded to blinatumomab, they received three additional cycles of treatment or proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). In this study, patients were followed until they reached a primary endpoint of hematological complete respCR or CR with partial hematological recovery (CRh*) within a course of two cycles of blinatumomab. Secondary endpoints included overall survival and safety.
The investigators reported a 68% (17 out of 25) hematological CR/CRh* rate; 5 of 17 responders (29%) had a CRh*. Minimal residual disease was reached in most respondents within the first two cycles. Six patients proceeded to HSCT in CR/CRh* after blinatumomab treatment, and one of them developed a medullary CD19-negative relapse after HSCT. Of the 11 patients that did not receive HSCT, 5 relapsed: 2 CD19-negative (one medullary and one extramedullary) and 3 CD19-positive (one medullary and 2 extramedullary).
Final dose and schedule of blinatumomab was 5 µg/m²/day (week 1); 15 µg/m²/day (remaining treatment in cohort 2a and 3). The most common treatment-emergent adverse events (TEAEs, all grade 1–2): pyrexia (67%), headache (33%) and tremor (33%); TEAEs of grade ≥3 (7 in 5 patients): were infections, confusion, epilepsy, hypertension, and thrombocytopenia.
The investigators concluded that “the final dosing regimen of blinatumomab produced an exceptionally high CR and was well-tolerated. A global Phase 2 study to confirm these data is underway.”