Reduced Intensity Conditioning (RIC) Transplant with Very Low Dose Evomela Is Safe and Effective in Patients with Hematologic Malignancies Undergoing Haploidentical Donor Transplant.

Background Melphalan (Mel) based conditioning provides favorable disease control for hematologic malignancies but is limited by regimen related toxicity. Propylene glycol-free melphalan HCL (Evomela) has greater bioavailability and avoids propylene glycol and its associated toxicities. With this favorable profile, we performed a Phase II study evaluating the safety and efficacy of the Evomela formulation of Mel, as conditioning in pts undergoing RIC HCT with a haploidentical donor. Methods We enrolled adult pts with a hematologic malignancy undergoing related donor haploidentical transplant with planned RIC conditioning. We enrolled to three cohorts: 1 - Fludarabine (Flu) 40mg/m2 x4, Mel140mg/m2, TBI200cGy, 2 - FluMel100TBI400, and to an amended cohort 3 - FluMel70TBI200. All pts received PTCy, Tac, MMF for GVHD prophylaxis. The primary endpoints of this study were non-relapse mortality (NRM) and relapse free survival (RFS) at 1 year. Secondary endpoints include primary graft failure, aGVHD at 100 and 180 days, and cGVHD at 1 year, and OS. Results 42 pts enrolled to study, by cohort: FluMel140TBI200 (n=10), FluMel100TBI400 (n=2), and FluMel70TBI200 (n=30). Median age for all pts was 62y (23-75y). Most common HCT indication was AML (n=18), lymphoma (n=12), MPN/MDS (n=7). Graft source was PB in 33 pt, BM in 9 pts. Median follow-up of survivors was 12 mo. Engraftment occurred in all patients surviving 30+ days. In the FluMel140TBI200 cohort, median age was 45y, 1yr NRM was 20%, 1yr RFS was 80%, and 2yr OS was 65%. Incidence of G3/4 aGVHD by D180 was 30%, and mod/severe cGVHD by 1yr was 20%. In the FluMel100TBI400 cohort, 2 of 2 pts died within D100, this cohort was closed. We amended the protocol and enrolled pts to a FluMel70TBI200 cohort, median age was 65y, 1yr NRM was 16%, 1yr RFS was 64%, and 2yr OS was 55%. No pts had G3/4 aGVHD by D180, and mod/severe cGVHD by 1yr was 3%. Conclusion In the haploidentical donor setting, Evomela based RIC is safe and effective at both 140mg/m2 and 70mg/m2 doses, in combination with fludarabine and TBI 200cGy. In younger pts, 140mg/m2 was tolerable with excellent disease control. In older pts, 70mg/m2 enabled reliable engraftment, low rates of severe GVHD, low NRM, and favorable disease control.