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Anti-CD40 Antibody Iomab-B Succeeds in Engraftment During Phase 3 Trial in AML
Success rates from the SIERRA trial, a phase 3 study of Iomab-B in elderly patients with relapsed or refractory (R/R) acute myeloid leukemia (AML), were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
“The SIERRA trial has been investigating the use of Iomab-B, an 131I-labeled anti-CD45 monoclonal antibody, to reduce relapse in patients with active R/R AML who receive hematopoietic cell transplant (HCT) as compared to conventional care (CC) therapies,” explained Boglarka Gyurkocza, MD, Memorial Sloan Kettering Cancer Center, New York, and co-investigators.
Recent approvals of the following targeted therapies like BCL-2 inhibitors, FLT-3 inhibitors, and IDH inhibitors have influenced an amendment to the trial to include refractory patients. Further, the researchers reported the success rate of engraftment and tolerability of Iomab-B among CC patients who cross-over to receive Iomab-B and HCT after failing these agents.
In all, 150 patients older than 55 years old with R/R AML were enrolled and randomized on a 1:1 basis to receive Iomab-B followed by fludarabine, total body irradiation 2 Gray (Gy), and allogeneic HCT, or to CC. CC patients were inducted to their physician’s choice of therapy, including targeted therapies, and may proceed to standard of care allogenic HCT if they achieve complete remission (CR).
“Available data for 136 patients, with a median age 65, demonstrated a median of 3 (range, 1-7) prior lines of AML therapies. Median marrow blast at time of study entry was 25 percent. Prior to enrollment, 85 (63%) patients received targeted therapies, including BCL-2 inhibitors (62%), FLT-3 inhibitors (18%), IDH inhibitors (7%) and others (13%),” continued Dr Gyurkocza and co-authors.
All 50 evaluable patients in the Iomab-B group that received HCT successfully engrafted a median radiation dose delivered to marrow of 14.7 Gy (range, 4.6-44.6) with a median time to neutrophil and platelet engraftment of 14.5 (range, 9-28) and 18 (range, 4-58) days, respectively.
Among 63 patients randomized to the CC group, 11 (17%) achieved CR and proceeded to standard of care HCT without Iomab-B, while 52 (83%) did not respond to CC therapy. Further, 27 out of 63 (43%) CC patients received targeted therapy, of whom 21 received venetoclax with hypomethylating agents or low-dose cytarabine.
Adverse events of grade 3 or higher were reported in 103 transplanted patients in both groups. Incidences of febrile neutropenia was 37 percent versus 55 percent, sepsis 5 percent vs 30 percent, and mucositis 10 percent vs 20 percent in the Iomab-B group compared to the CC group.
“SIERRA trial patients not achieving CR with recently approved targeted therapies who then crossed-over to receive HCT with Iomab-B successfully engrafted. Time to engraftment was similar to those who were randomized to receive Iomab-B and HCT. Available data suggest incidences of sepsis and mucositis are lower in the Iomab-B group,” concluded Dr Gyurkocza, et al.—Alexa Stoia
Hussein S, Chen P, Medeiros J, et al. Artificial Intelligence-Assisted Mapping of Proliferation Centers in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Identifies Patterns That Reliably Distinguish Accelerated Phase and Large Cell Transformation. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 1791.
