Safety and efficacy of CPX-351 in younger patients < 60 years old with secondary acute myeloid leukemia: An updated analysis.

Abstract

e18530 Background: Patients (pts) with secondary acute myeloid leukemia (s-AML) have poor long-term outcomes following standard induction chemotherapy with 7+3. In 2017 CPX-351 was FDA approved for upfront treatment of s-AML. The phase 3 trial demonstrated improved overall survival in pts aged 60-75 years old. Although CPX-351 treatment is indicated in all adults with s-AML, it is unclear whether CPX-351 is safe and effective in younger pts < 60 years. We sought to address this unanswered question by retrospective review of clinical experience since FDA approval. Methods: Medical records were retrospectively reviewed at five large academic centers to identify pts aged 18-59 years old with untreated s-AML, prior cytotoxic therapy, or AML-MRC treated with CPX-351 as induction therapy. Results: 30 pts with confirmed s-AML received CPX-351 therapy. Mean age was 53 years (range 23 – 59), 18 were male (60%). The majority (60%, N = 18) had AML-MRC, 7 (23%) had treatment-related AML (t-AML) and 6 (20%) had antecedent MDS. 6 pts had received prior HMA therapy. 19 pts had a complex karyotype (70%), and 4 patients were found to have a normal karyotype (15%). The most common molecular event was TP53 mutation observed in 10 pts (36%), followed by FLT3-ITD identified in 4 pts (14%). Overall response rate (CR/CRi/PR) was 46.7% with 5 CR (17.2%), 3 CRi (10.3%), and 6 PR (20.7%). The remaining pts (15/29, 51.7%) were non-responders. 8 pts have received an allogenic stem cell transplant. The most common AE was infection (80%, 24/30) with 4 clinically significant bleeding events. Thirty-day mortality was 13.3%, with 60-day mortality of 16.7%. Overall survival was 7 months (range 0.5 – 12.4 months), with mean follow up of 4.4 months. Conclusions: This multi-institutional retrospective analysis suggests that CPX-351 results in lower response rates (CR/CRi 27.6%) and shorter overall survival (7 mos) than reported in the recently published phase 3 trial in pts aged 60-75 years old. Potential explanations for this discrepancy include short follow up, small sample size, retrospective design, and the significant proportions of pts with complex karyotype and TP53 mutations. Historically, patients < 65 years old with s-AML have had a reported overall survival of approximately 7 months. Further investigation of this regimen in younger pts with s-AML as compared with 7+3 and other approaches is warranted.