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4932 Outcomes with Venetoclax and Hypomethylating Agents in Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up, Complications, and Disease Recurrence: Poster III
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Clinical Practice (Health Services and Quality), Diseases, Treatment Considerations, Myeloid Malignancies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Moazzam Shahzad, MD1,2,3, Aqsa Mumtaz, MD, MBBS2,3*, Ahmad Basharat2,3*, Sohaib Irfan, MD2,3*, Muhammad Hamza Sadiq, MBBS2,3*, Faryal Altaf, MD2,3*, Sarah Faisal2,3*, Numan Akram2,3*, Muhammad Zeeshan2,3*, Muhammad Kashif Amin, MD2,3,4*, Sibgha Gull Chaudhary, MD2,3,4*, Iqra Anwar, MBBS2,3,4*, Matthew McGuirk2,3,4*, Anurag Singh, MD2,3* and Muhammad Umair Mushtaq, MD2,3,4

1H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
2Mikael Rayaan Foundation Global Health Consortium, Kansas City, KS
3Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
4US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS

Introduction:

Venetoclax, a BCL-2 inhibitor, has emerged as a valuable option in the management of relapsed acute myeloid leukemia (AML) post-allogeneic hematopoietic stem cell transplantation (HSCT). Its efficacy, in combination with hypomethylating agents (HMAs) such as azacitidine and decitabine, has been promising and has been recently approved for the treatment of relapsed AML. This systematic review and meta-analysis aimed to evaluate the effectiveness of venetoclax with hypomethylating agents for relapsed AML after HSCT.

Methods:

Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Cochrane, and ClinicalTrials.gov databases until April 2024. Keywords used included relapsed acute myeloid leukemia, hematopoietic stem cell transplant, and venetoclax. Out of 44 identified studies, 13 met the inclusion criteria for pooled analysis. The inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with the 95% confidence intervals (CI) were extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.3.3).


Results:

We included 337 AML patients from 13 studies who relapsed after HSCT and were treated with venetoclax and hypomethylating agents. Ten (77%) studies were retrospective and 3 (23%) were prospective. The median age of patients was 58.5 years (35.2-66) and 50% were male (163 out of 326). The median follow-up duration was 15.3 months (2.7 to 20.1). The median time to relapse after HSCT, reported in 9 studies, was 7 months (1.6-9). The median overall survival was recorded at 8.58 months. Among the 8 studies reporting ELN risk categories, favorable (n=26), intermediate (n=65), intermediate-high risk (n=18), and adverse risk (n=123) were observed. Donor types for HSCT were available for 142 patients, with the distribution as follows: matched related/sibling donor (MRD/MSD, n=38), haploidentical donor(Haplo, n=31), matched unrelated donor (MUD, n=63), and mismatched unrelated donor (MMUD, n=10). Venetoclax was used in combination with HMA in all patients, with azacitidine (AZA) in 62% and with decitabine (DEC) in 38% of the patients. Donor lymphocyte infusions (DLI) were utilized in 27% of the patients. The pooled overall response rate (ORR) was 52% (95% CI 40-64%, I²=73%, p<0.01), and the pooled complete response (CR) and CR with incomplete count recovery (CRi) was 39% (95% CI 28-50%, I²=70%, p<0.01). The pooled 6- month overall survival (OS) was 51% (95% CI 24-77%, I²=77%, p<0.01), while the 1-year OS was 29% (95% CI 11-58%, I²=82%, p<0.01). The pooled mortality rate was 29% (95% CI, 9-64%, I²=89%, p<0.01). Our study analyzed the incidence of three common (grade III-IV) adverse events including neutropenia (73%, 95% CI 63-82%, I²=13%, p=0.33), thrombocytopenia (71%, 95% CI 62-79%, I²=33%, p=0.20), and infections (31%, 95% CI 14-56%, I²=89%, p<0.01).

Conclusion:

Venetoclax in combination with hypomethylating agents showed promising efficacy in the treatment of relapsed AML post-HSCT. However, the significant heterogeneity and high mortality rate observed underscores the need for further research and novel therapeutic strategies such as chimeric antigen receptor T-cell therapy followed by a reduced intensity allogeneic HSCT to achieve better outcomes.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH