Outcome of Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents Plus Venetoclax: A Single Center Experience in Resource Constrained Setting
Authors: Peter Hina , Ahmed Parvez , Mahmood Syed Karman , Ur Rahman Khalil , Barlas Sidra , Bahadur Laila , Chaudhry Qamar Un Nisa , Badshah Asad Ali , Naseeb Summaira , Fatima Mehroz , Ghazanfar Ayesha , Abbasi Sumyyia 
Published: December 2024

Background :
The patients of AML with poor functional status and existing co-morbidities have limited treatment options especially in countries with suboptimal health care facilities. Recent studies have shown promising results of HMA plus ventoclax in this group of patients. Pathwel Center of Hematology and Bone Marrow Transplant (BMT), has recently been established as a non-profit facility for treatment of hematological diseases for financially non affording patients. The center has introduced certain innovative strategies to make the treatment sustainable for poor patients in the limited available resources.
Objective :
To assess response of hypomethylating agents (HMA) plus Venetoclax in patients with AML treated at Pathwel Centre of Hematology and BMT, Rawalpindi Pakistan
Methods :
Study Design : Cross Sectional Observational Study.
Patients with AML registered at Pathwel Centre of Hematology and BMT who received HMA plus venetoclax from March 2022 to July 2024 were included in the analysis. The patient population consisted of patients with AML who were not eligible for intensive induction chemotherapy due to co-morbidities and received HMA plus venetoclax. Twelve patients received decitabine while 4 received azacytidine and 5 received both as HMA agent. Patient's medical records were reviewed and data entered in SPSS version 23 for statistical analysis. The primary outcome measure was response to HMA Plus venetoclax.
Results: A total of 21 patient received HMA plus venetoclax out of which 12 (57%) were male and 9 (43%) female. Median age was 37(range17-56). As per WHO 2022 classification 3 patients had AML MRC,17(80%) had AML NOS, 4 AML M0, 3 AML M1 ,3 AML M2, 3 AML M4, 1 had acute leukemia with ambiguous lineage. Of the 21 patients 5 had AML with recurrent genetic abnormalities, 2 bcr abl, 2 NPM1, 1 CBFB MYH11. The patients were risk stratified according to ELN 2022 risk classification into good risk (3 patients), high risk (2 patients) and intermediate risk (16 patients). Indications for giving HMA+ venetoclax were relapsed disease in 2 patients, refractory disease in 8, poor performance status in 9. Two patients did not have financial resources for induction chemotherapy. Median number of HMA+ venetoclax cycles given were 2 (range 1-7). Median number of cycles to achieve remission was 1(range1-4). Overall response rate (ORR) was 57% (n=12) including 10 (47%) in CR and 1(4%) in partial remission (PR). One patient with AML transforming from primary myelofibrosis continued to have fibrosis with no residual blasts. Of the 11(52%) patients that responded 7 responded after 1 cycle, 2 after 2 cycles 1 after 3 and 1 after 4 cycles. Three 3 patients did not respond to HMA+ venetoclax. Four patients with CR relapsed during follow up, 3 died while 1 is on palliative care. Three patients were lost to follow up. Three patients underwent HSCT after achieving remission with HMA +ventoclax, out of them 2 are in CR at day 85 and 134 post BMT while 1 relapsed at day 139. Median overall survival was 6.4 months with median OS in patients achieving CR 6.8 months and median disease free survival DFS was 5.3 months. Various complications seen included prolonged cytopenias, febrile neutropenia, invasive aspergillosis, thrombophlebitis and perianal abscess. There was no treatment related mortality seen in these patients.
Conclusion
Use of HMA+ Venetoclax in AML with relapsed/refractory disease or co-morbidities improves the overall survival with reasonable quality of life. Our results of OS and DFS are slightly inferior to the reported data in advanced countries. Further optimization of the health care facilities may lead to improvement in survival rates among this population of patients.
Key Words :
Hypomethylating agents, Venetoclax, Acute Myeloid Leukemia