1.
Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation for B-lineage Acute Lymphoblastic Leukemia
Gaballa, M. R., Banerjee, P. P., Milton, D. R., Jiang, X., Ganesh, C., Khazal, S. J., Nandivada, V., Islam, S., Kaplan, M., Daher, M., et al
Blood. 2021
Abstract
Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single center phase II study evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least one cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44-105). Twelve patients (57%) completed all 4 treatment cycles. Neutropenia was the only grade 4 adverse event (19%). Rates of cytokine release (5% G1) and neurotoxicity (5% G2) were minimal. The cumulative incidence of acute GVHD grades 2-4 and 3-4 were 33% and 5%, respectively; two cases of mild (10%) and one case of moderate (5%) chronic GVHD were noted. With a median follow-up of 14.3 months, the 1-year overall survival, progression-free survival, and non-relapse mortality rates were 85%, 71%, and 0%, respectively. In a matched-analysis with a contemporary cohort of 57 patients, we found no significant difference between groups regarding blinatumomab's efficacy. Correlative studies of baseline and post-treatment samples identified patients with specific T-cell profiles as "responders" or "non-responders" to therapy. Responders had higher proportions of effector memory CD8 T-cell subsets. Non-responders were T-cell deficient and expressed more inhibitory checkpoint molecules, including TIM3. We found that blinatumomab post-allogeneic HCT is feasible, and its benefit is dependent on the immune milieu at time of treatment.
2.
Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for High-Risk Acute Lymphoblastic Leukemia
Srour, S. A., Milton, D. R., Bashey, A., Karduss-Urueta, A., Al Malki, M. M., Romee, R., Solomon, S., Nademanee, A., Brown, S., Slade, M., et al
Biology of Blood & Marrow Transplantation. 2017;23(2):318-324
Abstract
Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months. Thirty-two patients were in first complete remission (CR1), while the rest were beyond CR1. Neutrophil engraftment occurred in 95% of the patients. The cumulative incidences of grades II to IV and III and IV acute GVHD at day 100 after transplantation were 32% and 11%, respectively, whereas chronic GVHD, nonrelapse mortality, relapse rate, and disease-free survival (DFS) at 1 year after transplantation were 32%, 21%, 27%, and 51%, respectively. Patients in CR1 had 52% DFS at 3 years. These results suggest that haploidentical transplants performed with PTCy-based GVHD prophylaxis provide a very suitable alternative to HLA-matched transplantations for patients with ALL.