Outcomes Following Second Allogenic Haematopoietic Cell Transplantation in Patients with Myelofibrosis: A Retrospective Study on Behalf of the Chronic Malignancies Working Party of EBMT

Introduction: The only curative treatment for myelofibrosis (MF) remains allogenic haematopoietic cell transplantation (allo-HCT) although the risks of non-relapse mortality (NRM), relapse and graft rejection need to be taken into consideration. Therapeutic approaches following relapse after allo-HCT include symptom-directed management, chemotherapy, JAK2 inhibitors, adoptive immunotherapeutic approaches with donor lymphocyte infusion (DLI) and, in a minority, a second allo-HCT. Frequently, due to the advanced age of the recipient, early relapses, and numerous complications, 2nd allo-HCT can only be considered in a limited number of patients. Few studies evaluating the role of 2nd allo-HCT in MF following 1st relapse or primary/secondary graft rejection have been published to date. Methods and results: Patient selection was performed by identifying adult patients who underwent 2nd allo-HCT for MF between 2010-2017: 216 patients were analyzed; 64% were male, 78% had primary MF (PMF) and 22% secondary MF (sMF). Median age at the time of 2nd allo-HCT was 57 years, and median time from 1st allo-HCT was 8 months. Of this cohort, 56% of patients received a 2nd allo-HCT for relapse, 31% for graft failure and the reason was missing in 13%. A greater proportion was transplanted within 1 year from 1st allo-HCT (61 %) whilst 39% had 2nd allo-HCT > 1 year. A reduced Karnofsky performance status (KPS 12 months, p=0.02). The 2-year relapse-free-survival (RFS) for the entire cohort was 44%. Only time elapsed from the 1st allo-HCT to 2nd was significantly associated with 2-year RFS (41% for ≤12 months, 49% for >12 months, p=0.05). Of note, the 2-year OS and RFS were comparable following use of the same or a different donor. The 2-year cumulative incidence of relapse and NRM were 22 and 34%, respectively. The time interval from 1st to 2nd allo-HCT appeared to be highly significant for NRM with patients transplanted ≤12 months having a higher 2-year NRM compared to those transplanted >12 months (40 vs 24%, respectively, p=0.008). A trend for higher NRM was the reason for 2nd allo-HCT: patients transplanted for graft rejection had a 2-year NRM of 45% compared to 31% for those with relapse (p=0.06). Conclusions: This analysis supports the utilization of a 2nd allo-HCT for patients with MF who have presented with graft failure or relapse following a 1st allo-HCT. In univariate analysis, overall outcome appears worse in patients being transplanted after graft failure as well as for those transplanted within 1 year after 1st allo-HCT, due to increased NRM. Of note, the use of either the original or a different donor are associated with similar outcomes. Further work is required to elucidate other risk factors, GVHD rates and to define the optimal conditioning regimen in this setting. Download : Download high-res image (495KB) Download : Download full-size image Table . Disclosures Robin: Novartis Neovii: Research Funding. Kroger: Sanofi-Aventis: Honoraria; Riemser: Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Medac: Honoraria; JAZZ: Honoraria; DKMS: Research Funding; Celgene: Honoraria, Research Funding. Angelucci: Celgene: Honoraria, Other: Participation in DMC; BlueBirdBio: Other: Local advisory board; Jazz Pharmaceuticals: Other: Local advisory board; Roche: Other: Local advisory board; Vertex Pharmaceuticals Incorp., and CRISPR Therapeutics: Other: Participation in DMC; Novatis: Honoraria, Other: Chair Steering Committee TELESTO protocol. Dreger: AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; Neovii, Riemser: Research Funding. Platzbecker: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Rambaldi: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mayer: AOP Orphan Pharmaceuticals AG: Research Funding. Ladetto: ADC Therapeutics: Honoraria; Pfizer: Honoraria, Speakers Bureau; Celgene: Honoraria; JJ Roche: Honoraria; AbbVie: Honoraria; Acerta: Honoraria, Speakers Bureau. Hernandez Boluda: Incyte: Other: Travel expenses paid. McLornan: Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria. Chalandon: Incyte Biosciences: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.