David A. Sallman, MD
Two experts in myelodysplastic syndromes (MDS) discussed the findings on the combination of venetoclax plus azacitidine in the treatment of higher-risk MDS with The ASCO Post. David A. Sallman, MD, Assistant Member in the Department of Malignant Hematology, Moffit Cancer Center, Tampa, provided these thoughts: “The data are good—with a median duration of response of 16 months and a median survival of 26 months—but they are not so good that I am assured the ongoing phase III trial will be positive.” He referenced the findings for the anti-CD47 immunotherapy magrolimab, which appeared promising in phase II trials1 but failed to provide a benefit in the phase III ENHANCE trial (unpublished data).
“When we presented our [phase II] magrolimab data, we also had a true complete remission rate of 33% and a median overall survival of about 2 years. The Kaplan-Meier curve for azacitidine plus venetoclax in this phase Ib study is pretty similar. Though the overall response rate is higher [vs azacitidine alone, historically], I think the true complete remission rate—the most valuable response—is lower or at least not dramatically different. The biggest benefit of venetoclax is in getting patients to transplant,” Dr. Sallman said.
Further Commentary
Mikkael A. Sekeres, MD, Professor of Medicine and Chief of the Division of Hematology, Sylvester Cancer Center, University of Miami Health System, also commented on the response data, suggesting more clarity was needed to understand how patients truly responded to azacitidine plus venetoclax. Although investigators calculated the rates of complete remissions, marrow complete remissions, and marrow complete remissions with hematologic improvement, Dr. Sekeres noted that marrow complete remission is no longer considered a particularly important endpoint.
Mikkael A. Sekeres, MD
“Our MDS Clinical Research Consortium has shown that patients with a marrow complete remission have no different outcomes than those with stable disease, which is why in the 2023 iteration of the MDS response criteria, we eliminated marrow complete remissions…. The responses we want to focus on in patients with higher-risk MDS are complete remission and hematologic improvement,” he said. It was not clear, he continued, what proportion of patients had hematologic improvement alone, and the actual overall response rate was not clear.
Dr. Sekeres also thought the duration of response and overall survival were not much better than those achieved with azacitidine alone. “Is venetoclax adding anything?” he asked. “I hope so. My concern is that in patients with higher-risk MDS, who have more of a bone marrow failure state than patients with leukemia, the drug may be adding toxicity, but we don’t know yet. We have seen many randomized trials fail, after we were enthusiastic going into them.”
DISCLOSURE: Dr. Sallman reported financial relationships with AbbVie, Affirmed Gmbh, Gilead Sciences, Incyte, Intellisphere, Molecular Partners AG, PGEN Therapeutics, Takeda, Zetalis, AvenCell, BlueBird Bio, BMS, Intellia, Jasper Therapeutics, Kite Pharma, Magenta Therapeutics, NKARTA, Novartis, and Orbita. Dr. Sekeres reported financial relationships with BMS, Geron, Kurome, and Novartis.
REFERENCE
1. Sallman DA, Al Malki MM, Asch AS, et al: Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: Final results of a phase Ib study. J Clin Oncol 41:2815-2826, 2023.
