Liposomal Daunorubicin/Cytarabine As a Bridge to Second Allogeneic Transplant for Early Relapses after First Allograft for Acute Myelogenous Leukemia/Myelodysplastic Syndrome

Abstract

Introduction Liposomal daunorubicin/cytarabine (Vyxeos® or lipo-CD) is a dual drug liposomal encapsulation, delivering these drugs at a fixed 1:5 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, lipo-CD pts had improved survival and remission rates in a pivotal phase III study, with more reaching allogeneic transplantation (HCT), with lower post-HCT mortality and improved survival. With its enhanced pharmacokinetics, lipo-CD may provide a potent bridge to second transplant for early relapses after HCT. Here, we report our experience. Methods We retrospectively reviewed recipients of lipo-CD at our institution since FDA approval 8/2017. Of 23 pts, 8 relapsed Results Median age was 60 yrs. They received 1-4 lines of therapy (median 2) prior to first HCT with 5/8 pts having received 7+3 (cytarabine 100-200mg/m2 × 7 days + dauno 60-90mg/m2 × 3 days). 6 had adverse cytogenetics/genomic profiles. 7/8 had AML and 1 high grade MDS. Pts relapsed at 2 to 7 mo (median 4 mo) after first HCT, and all 8 received full lipo-CD induction (dauno 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy. [Table] 7/8 had Day 14 bone marrow biopsies: 3 were clear, 2 had >80% cytoreduction, and 2 had similar blast count. 3 with persistent disease underwent re-induction with lipo-CD (Days 1 and 3). All successfully proceeded to second transplant at 15-70 days after lipo-CD: 7 with same donor after melphalan 140mg/m2, and 1 from a different donor after busulfan/fludarabine. Tacrolimus was started on day + 7 and discontinued at day + 28 if no GVHD. 4/8 remain alive. 2 relapsed at 3 and 6 months post-HCT and are remarkably in CR at 19 and 16 mo after second transplant despite isolated CNS relapses, which were successfully treated. The other two relapsed at 2 and 3 mo post-HCT and are alive after second transplant. Conclusion Outpatient lipo-CD as a bridge to second transplant is feasible and effective in treating AML/MDS with early relapse after first HCT. While preliminary, survival appears favorable to that reported (14-23% at 1 year) in this very poor risk group, including those with adverse cytogenetics. Prospective multi-center trials are planned.