Gemtuzumab Ozogamicin in Favorable and Intermediate Risk Acute Myeloid Leukemia: A Single-Center Experience

Background

Acute Myeloid Leukemia (AML) is a common form of leukemia in adults. Gemtuzumab Ozogamicin (GO), an anti-CD33 antibody linked to a chemotherapy molecule, demonstrated improved event-free survival (EFS) and overall survival (OS) in favorable and intermediate risk AML when given with standard induction chemotherapy.

Purpose

This retrospective study will examine outcomes of AML patients at the McGill University Health Center (MUHC) who received GO with standard induction chemotherapy compared to induction chemotherapy alone.

Methods

We selected favorable and intermediate risk AML patients who received GO with induction chemotherapy from January 1, 2015, to November 23, 2023, with matched controls based on cytogenetic and molecular characteristics. The European LeukemiaNet AML classification was used, noting that the ALFA-0701 study identified favorable patients based on cytogenetics and NPM1 or CEBPA mutations. We extracted age, sex, length of hospital stays, complete remission (CR), time to neutrophil (ANC >1.0) and platelet (platelet >50 and >100) recovery, hepatic toxicity (bilirubin >1.5x upper limit of normal (ULN), transaminases >3x ULN, or veno-occlusive disease (VOD)), stem cell transplantation (SCT), relapse rate, and survival. We performed statistical analysis to obtain hazard ratios (HR) and odds ratios (OR).

Results

Our cohort had 16 GO and 16 control patients, evenly distributed across favorable and intermediate AML risk categories. GO patients received treatment between 2020 and 2023, and controls between 2016 and 2022. Median age was 56.0 years (range 19-71) in GO and 53.5 years (range 23-71) in controls. Both groups had 63% male patients. Mean duration of follow-up was 12.8 months in GO and 39.8 months in controls. There was no increase in hepatic toxicity in GO compared to controls (19% versus 25%; OR 0.69, 95% CI 0.13-3.75), no longer mean platelet recovery time (plt >50 in 26.8 days vs. 27.0 days; HR 0.58, 95% CI 0.28-1.20) nor longer mean neutrophil recovery time (ANC >1.0 in 32.4 days vs. 30.5 days; HR 0.79, 95% CI 0.39-1.59). Other parameters did not demonstrate statistical significance in GO compared to controls, including mean length of stay (37.9 days vs. 37.8 days; HR 0.879, 95% CI 0.43-1.78), CR (88% vs. 94%; HR 1.65, 95% CI 0.32-8.58), one-year relapse (12.5% vs. 6.3%; OR 2.14 95% CI 0.17-26.33), and one-year survival (93.8% vs. 87.0%; OR 2.31 95% CI 0.19-28.47). GO patients showed a trend to being less likely to receive SCT.

Conclusion

GO was well-tolerated with no increase in delayed cell count recovery or hepatic toxicity, in contrast to the ALFA-0701 study. There were no significant differences in CR or relapse rates. A trend towards decreased SCT was observed with GO, which was likely due to the selection of more non-transplant candidates in the intermediate risk group to receive GO, based on the consideration that they would benefit the most. The absence of significant differences may be due to the small cohort size and short follow-up time. Further evaluation of this cohort will help clarify these outcomes.

Storring:Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trails, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trails, Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trails, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trails, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Taiho: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Syndax: Other: Clinical Trails. Popradi:Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Kyowa Kirin: Consultancy, Honoraria; Mallinckrodt: Consultancy, Honoraria; Medexus: Consultancy, Honoraria; Novaris: Consultancy, Honoraria; Sean Gen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Servier: Honoraria; Sobi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.