Real-World Safety and Efficacy of Gemtuzumab Ozogamicin in Relapsed or Refractory AML

Background: Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate with a dubious history after initial FDA approval in 2000 and subsequent voluntary withdrawal from the market when subsequent trials failed to demonstrate clinical benefit and signaled safety concerns. It received renewed interest in 2017 on a new dosing schedule and is currently approved in upfront setting for favorable risk AML along with intensive induction, as well as monotherapy in the relapsed/refractory (R/R) setting. Real-world safety and efficacy data for use of GO as monotherapy are lacking in elderly patients, with most reported cohorts at a sample size of 10 - 20. The aim of this study was to contribute real-world efficacy data of gemtuzumab ozogamicin in relapsed/refractory AML. Patients & Methods: We analyzed 15 patients receiving GO for R/R AML from January 2016 to December 2021 at VCU Massey Cancer Center. Patient and disease characteristics, treatment histories, toxicities, and responses were obtained via retrospective analysis. Patients were considered evaluable for response if there was a bone marrow biopsy following a minimum of 28 days of treatment. The event for calculating the overall survival (OS) was the date of death. Patients were otherwise censored at the date of last contact. Results: The median age of patients receiving GO was 72 years (range: 34 - 84 years), 9 were male (60.0%), the median ECOG score was 1, and the median Charleston Comorbidity Index (CCI) score was 6. Risk stratification via ELN 2017 categorization at the time of AML diagnosis was favorable in 3 (20.0%), intermediate in 6 (40.0%), and adverse in 6 (40.0%). The median number of lines of therapy prior to receipt of GO was 2 and all patients received 1 cycle of GO. Rates of toxicities were high, with grade 1 toxicity of any type observed in 69.2% of patients, grade 2 in 61.5%, grade 3 in 92.4%, and grade 4 in 100%. The most common high-grade (grade ≥3) toxicities were hematological. Of the grade ≥3 non-hematologic toxicities, the most common was neutropenic fever (50%), with remaining high-grade toxicities occurring at a rate of less than 8.3%, including AST elevation, ALP elevation, and acute kidney injury. In patients that were evaluable, the composite response rate (CRR; CR+ CRi) was 20.0%. Of the responders, one (50%) had intermediate and one (50%) had adverse risk cytogenetic/molecular profiling. Both patients had FLT3-ITDmut. Following receipt of GO, 15.4% died within 30 days and 7.7% died within 60 days. The median overall survival (OS) was 4.8 months. Conclusions: Gemtuzumab ozogamicin offers only a modest survival benefit as monotherapy with significant risk of high-grade toxicities in R/R AML. However, some CRs were observed in this heavily pre-treated population, illustrating a potential role for GO as a bridge to other therapeutic options, including clinical trial availability or allogeneic hematopoietic stem cell transplant.