ASH 2023: Azacitidine and Venetoclax for High-risk MDS Patients

Dr. Jacqueline Garcia, a medical oncologist specializing in myelodysplastic syndromes (MDS) at Dana Farber Cancer Institute is excited to share groundbreaking insights from a recent presentation at the American Society of Hematology (ASH) meeting in 2023, offering new hope and potential breakthroughs for individuals facing MDS.

Dr. Garcia had the opportunity to present data from an ongoing Phase 1B clinical trial featuring azacitidine combined with venetoclax, for frontline therapy in high-risk MDS. Azacitidine is a medication that helps normalize blood cell production, while venetoclax is an oral BCL2 inhibitor designed to target specific proteins involved in cancer cell survival. In Dr. Garcia's presentation, she shared updates on treatment responses and survival outcomes among those receiving this combination therapy at the recommended phase 2 dose. Dr. Garcia also mentions that there is an ongoing randomized, double-blinded Phase 3 study comparing this combination against the current standard of care which is azacitine alone.

Patient Characteristics

The study included 107 patients with higher-risk MDS, with 85% falling into the high or very high-risk category based on IPSS-R criteria. This group represented a high-risk cohort with common mutations observed, such as ASXL1, RUNX1, and p-53, with SRSF2 being the most frequent. Most patients had well over 5% bone marrow blasts upon study entry, representing a traditional high-risk MDS patient cohort.

Treatment Details

Patients in the trial received azacitidine intravenously or subcutaneously for 7 days in a 28-day cycle, combined with oral venetoclax given on days 1 through 14, with a 2-day break. The safety profile was reassuring, with expected lower blood counts and manageable febrile neutropenia (a high temperature with low neutrophil levels).

Encouraging Outcomes

The outcomes of this trial were exceptionally promising. More than 80% of patients who received the azacitidine and venetoclax combination responded to this therapy. A 30% complete remission rate was observed by the IWG 2006 criteria, and additional responses, including marrow complete remission with hematologic improvement, were seen in 37% of patients. Importantly, patients achieved transfusion independence in well over 40% of cases. 

Survival and Length of Remission

The median overall survival for the 107 patients was an impressive 26 months, with survival for patients in complete remission not yet reached. The median duration of complete remission was approximately 16 and 1/2 months. At the 12-month mark, 71% of patients were alive, while at the 24-month mark, 51% were still alive. 

What This Means for Patients

These findings offer new hope for individuals battling MDS. The combination therapy of azacitidine and venetoclax has shown impressive effectiveness, not only in achieving remission but also in extending survival. While these results are encouraging, ongoing research, including the open Phase 3 study mentioned by Dr. Garcia, will provide further insights into the long-term benefits and potential applications of this combination treatment. 

If you or a loved one is facing MDS, discussing these advancements with your healthcare team could open doors to new possibilities and renewed hope for the future. Stay informed, stay hopeful, and remember that the landscape of MDS treatment is evolving, bringing us closer to more effective and personalized care.