Comparison of Salvage Intensive Chemotherapy Versus Venetoclax Combined Regimen in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)
Authors: Park Silvia , Kim Hee-Je , Cho Byung Sik , Kim Yoo-Jin , Min Gi June , Park Sung-Soo , Yahng Seung-Ah , Jeon Young-Woo , Shin Seung-Hwan , Yoon Jae-Ho , Lee Sung-Eun , Eom Ki-Seong , Lee Seok , Min Chang-Ki , Cho Seok-Goo , Lee Jong Wook 
Published: November 2021

Abstract

Introduction: Venetoclax (VEN) combined regimen received FDA approval for newly diagnosed elderly or unfit acute myeloid leukemia (AML) patients. Recently, with increasing use as off-label for relapsed or refractory setting in real practice, the evidence that the regimen is potentially effective in R/R AML is emerging. However, there is no answer to the question how VEN combined treatment compares to intensive chemotherapy (IC) in R/R AML when the patients were intended to be cured with bridging to stem cell transplantation (SCT) after either of these treatments.
Methods: Adult AML patients (age ≥18 years) who were refractory to or relapsed after anthracycline plus cytarabine induction were subjected to this analysis. As a group of interest, R/R AML patients who received VEN combined regimen were screened first, and we found a total of 54 corresponding patients between Feb 2020 and Jan 2021. As a comparison, we searched historical controls who were treated with salvage IC during the past two years, revealing a total of 89 patients between Jan 2018 and Jan 2020. Patients analyzed here received VEN-combination or IC as their first or second-line salvage therapy.
Results: Overall, the median age was 49 years (range, 18 to 72), and the patients of first line salvage (n=125, 87.4%) were more included. When comparing IC and VEN-combination groups, there were no differences in age, sex, ELN risk groups, cytogenetics, disease type or mutation status. However, more patients in VEN-combination group were in their second line salvage setting (IC vs VEN-combination; 5.6% vs 24.1%, p&lt;0.001) and had received prior SCT (13.5% vs 38.5%, p&lt;0.001). The percentage of patients who had CR, CRi and MLFS were 39.3%, 6.0%, and 0.0% in IC group, and were 40.7%, 11.1%, and 7.4% in VEN group, yielding an overall response rate of 45.2% and 59.3%, respectively (p=0.108). Regarding the bridging to SCT, patients who underwent allo-SCT after salvage therapy were 69.7% in IC and 68.5% in VEN-combination group (p=0.886), of whom 62.9% (IC) and 86.5% (VEN-combination) of patients achieved either CR, CRi or MLFS at SCT (p=0.012). Of note, the median time to SCT were shorter in patients who received VEN-combined regimen (median, 103 days) compared to patients receiving IC (median, 139 days) (p=0.012). The median OS without censoring at the time of SCT were 334 days (95% CI, 198-469) and 381 days (95% CI, 345-416) in IC and VEN-combination group, respectively (p=0.592), after a median follow up period of 685 days and 345 days. VEN-combined regimen was significantly superior to IC in achieving response (p=0.031, OR=2.980 [95% CI 1.105-8.033]) and showed trend towards better survival (p=0.059, HR=0.454 [95% CI 0.200-1.030]) among the patients of fist-line salvage setting only, although significant differences were not shown in overall patients.
Conclusion: These findings suggest that VEN-combined treatment is a feasible option for R/R AML and could be chosen over salvage IC in R/R AML based on its anti-leukemic response, bridging to SCT with disease control and survival, which were comparable to IC in overall patients and were tended to be superior in patients of first salvage setting only.

Disclosures
Kim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees.

OffLabel Disclosure:
venetoclax use in R/R AML: off label use