Leukemia Fellow Highlights Modest Gains With Azacitidine-Venetoclax in HR-MDS Patients

Julie Braish, MBBCh, is a third-year fellow in the Leukemia Fellowship Program at The University of Texas MD Anderson Cancer Center, where she has been honing her expertise since July 2023. With a focus on the biology and treatment of leukemia, her research interests center on clonal hematopoiesis (CHIP), clonal cytopenia of undetermined significance (CCUS), and the role of inflammaging in leukemic transformation. Passionate about equitable cancer care, Dr. Braish volunteers with ASC-CAN to address healthcare disparities.

Originally from Lebanon, she earned her medical degree with distinction from Beirut Arab University in 2017, followed by postgraduate training at the American University of Beirut. She then completed an accelerated Internal Medicine residency at the University of Connecticut, where she was named “Intern of the Year” and graduated in just two years—an honor granted by the American Board of Internal Medicine.

Outside the clinic, Dr. Braish finds inspiration in the arts and nature, often painting or capturing landscapes during road trips with loved ones.

Azacitidine improves survival in high-risk myelodysplastic syndrome [HR-MDS] compared to conventional care, but outcomes remain poor after failure with a median overall survival [OS] of 5.6 months,” said Julie Braish, MBBCh, a clinical fellow, Department of Leukemia, The University of Texas MD Anderson Cancer Center (MD Anderson) told Blood Cancers Today.

Dr. Braish was a co-investigator of a phase 1/2 study conducted at MD Anderson under the leadership of Guillermo Garcia-Manero, MD, professor, Department of Leukemia and chief, Section of Myelodysplastic Syndromes, Division of Cancer Medicine. During The HemOnc Pulse Live! Fellows Panel Discussion, Braish presented data from the study, which evaluated the safety, tolerability, and efficacy of azacitidine and venetoclax in patients with HR-MDS and CMML.

“In our study, adding venetoclax post-HMA failure was feasible but did not meaningfully extend survival with a median OS of 7 months,” Dr. Braish said.

Results were from 33 patients who previously failed on four or more cycles of hypomethylating agent (HMA) therapy and no prior treatment with a BCL-2 inhibitor. Patients received azacitidine 75 mg/m² by intravenous or subcutaneous infusion for 5 days plus venetoclax 100-400 mg for 14 days in a 28-day cycle.

Results showed that the overall response rate (ORR) was 49% (95% CI, 31.4%-65.5%). Response data come from a phase 1 ORR of 58% (95% CI, 30.6%-86%) from a cohort of 12 patients and phase 2 ORR of 43% (95% CI, 21.7%-64%) from a cohort of 21 patients. Complete remission (CR) was observed in 3% (95% CI, 0%-9%). Marrow CR with hematologic improvement was shown in 24% (95% CI, 9.7%-38.8%), and 21% of patients (95% CI, 7.3%-35.2%) experienced marrow CR alone. The median number of cycles to the first response was one cycle (range, 1-4).

Median overall survival was estimated to be 7 months (95% CI, 3.5-10.5 months), and median progression-free survival was estimated to be 6 months (3.019-8.98 months).

Investigators also assessed efficacy in patients with key mutations, including TP53 and ASXL1. Of the 33 patients, 10 presented with TP53 mutations. In the TP53-positive cohort, the median OS was 3 months (95% CI, 0.9-5.0).

Fifteen patients presented with ASXL1 mutations, and among those patients, the median OS was 8 months (95% CI 3.5-13.4).

“Three of the four patients that remained alive at the time of last follow-up received a stem cell transplant, raising the question of this combination being used as a bridge to transplantation,” Dr. Braish explained.

Safety results showed that 68% of patients experienced low-grade treatment-emergent adverse events (TEAS). There were also grade 3 TEAEs in 20% of patients, grade 4 events in 10%, and grade 5 in 2%. The most common low-grade TEAEs were nausea and vomiting (16%), disturbed liver function tests (4%), neutropenia (2%), and thrombocytopenia (1%).

“I’m grateful as a fellow to learn from some of the world’s leading leukemia experts who are truly dedicated to teaching and supporting my growth,” said Dr. Braish, regarding her involvement in this research.

Reference

2nd Annual The HemOnc Pulse Live!; May 2-3, 2025; Austin, TX.