Nonmyeloablative Allogeneic Transplantation in First Remission for Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia with Post-Transplantation Cyclophosphamide: Outcomes By Receipt of Pre-Transplant Blinatumomab

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1846-1846
• Main Authors: Webster, Jonathan, Smith, B. Douglas, DeZern, Amy E., Ambinder, Alexander J., Levis, Mark, Showel, Margaret M., Prince, Gabrielle T., Gondek, Lukasz P., Ghiaur, Gabriel, Dalton, William Brian, Hourigan, Christopher S., Jain, Tania, Gladstone, Douglas E, Luznik, Leo, Imus, Philip H., Bolanos-Meade, Javier, Fuchs, Ephraim J., Gocke, Christian B., Ali, Abbas Abbas, Huff, Carol Ann, Borrello, Ivan M., Swinnen, Lode J., Wagner-Johnston, Nina D., Ambinder, Richard F., Jones, Richard J., Gojo, Ivana
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-153750

Background: The benefit of allogeneic blood or marrow transplantation (alloBMT) following myeloablative conditioning (MAC) in first complete remission (CR1) compared to chemotherapy has been demonstrated in a randomized trial for adults with acute lymphoblastic leukemia (ALL). Persistence of measurable residual disease (MRD) prior to alloBMT confers an increased risk of relapse. Blinatumomab eradicates persistent or recurrent MRD at levels ≥10 -3 in 78% of B ALL. However, post-hoc analyses of patients who have undergone alloBMT following blinatumomab for MRD demonstrate non-relapse mortality (NRM) of 36.5%. NRM following nonmyeloablative (NMAC) alloBMT with high-dose post-transplantation cyclophosphamide (PTCy) is just 11%. Given broadly similar outcomes between HLA-matched MAC alloBMT and HLA-haploidentical NMAC alloBMT following PTCy, we have shifted to using exclusively NMAC alloBMT with PTCy and sought to explore outcomes depending on receipt of pre-transplant blinatumomab. Methods: The bone marrow transplant database at Johns Hopkins was queried for adult patients with Ph-negative B-ALL who received NMAC alloBMT in CR1 using PTCy between January 2008 and July 2020. Characteristics of patients were summarized and compared using the student's T test for continuous variables and Fisher's exact test for categorical variables. Estimators of OS and RFS were reported using the Kaplan-Meier method. Differences in time-to-event outcomes were estimated using Cox proportional hazards model for OS and RFS, and Fine and Gray's model for cumulative incidence of relapse (CIR)/NRM considering competing events. Results: Among the 50 identified patients undergoing 1 st transplant in CR1 with NMAC, all received conditioning with fludarabine and cyclophosphamide followed by total body irradiation (TBI). In addition to PTCy, all patients received mycophenolate mofetil and either tacrolimus or sirolimus as GVHD prophylaxis. Sixteen patients (32%) received blinatumomab in CR1 or achieved CR1 following blinatumomab and proceeded to transplant without intervening therapy, while 34 patients (68%) did not. At the time of treatment with blinatumomab; 3 patients had >5% blasts after chemotherapy, 8 had persistent or recurrent MRD >10 -4 after chemotherapy, and 5 had no evidence of MRD at a sensitivity of 10 -4. Among the 5 MRD- patients treated with blinatumomab; 1 had been refractory to their first course of chemotherapy (67% blasts), 3 had MRD >10 -4 at the first MRD response a