Outcomes of Allogeneic Haematopoietic Stem Cell Transplantation for Therapy-Related Myeloid Neoplasms Following Treatment for Myeloma

Introduction

As the outcomes for patients with multiple myeloma continue to improve, therapy-related myeloid neoplasms (t-MN) are increasingly recognised as a treatment complication. The prognosis of tMDS is poor with life expectancy typically less than a year¹. There is limited data on the management of t-MN secondary to myeloma therapies. We performed a registry study on the outcomes of patients who underwent an allogeneic haematopoietic stem cell transplant (allo-HCT) for both therapy related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) following treatment for myeloma.

Methods

The European Society for Blood and Marrow Transplantation (EBMT) registry was used to identify 157 patients with t-MN across 96 centres between 2006-2018. The median age of patients was 62.1 years (57.6-66.7), with 63.7% male and 36.5% female. 100 patients were transplanted for t-AML and 57 for t-MDS with a median time from myeloma diagnosis to time of allo-HCT of 72.6 (46.1-102.9) months. The median time from t-MN diagnosis to allo-HCT was 6.4 (3.9-9.4) months. We examined overall survival (OS), progression free survival (PFS) relapse and non-relapse mortality (NRM) and myeloma recurrence. The median follow-up time was 64.9 months.

Results

The median survival time for all patients was 14.3 months. OS at 12- and 60 months was 55% and 27% respectively and PFS at 12- and 60 months was 45% and 24% respectively. The incidence of relapse of tMN at 12- and 60 months was 35% and 45% respectively, with NRM 20% and 31% respectively. The commonest cause of death was infection (36.3% n=37) followed by disease relapse/progression (34.3% n=35).

With respect to t-MN disease status 59% of patients with t-MN were in a complete remission at time of transplant. Cytogenetic results were available for all patients with 67.6% abnormal, 26.7% normal and failed/not done in 5.7% cases. IPPS-R was available in 58% of cases; Good 17(29.3%), intermediate 13(22.4%), poor 13(22.4%) and very poor 15(25.9%). Data on status of myeloma at time of allo-HCT was available in only 50 patients (CR 38%, VGPR 22%, PR 10%, stable disease 11% and progressive disease 8%). The majority of patients underwent matched unrelated transplant 79%(124) versus sibling allo 21% (n33). The majority had reduced intensity conditioning (RIC 70.3%, standard 29.7%, missing 1.3%).

130 patients had undergone prior autologous transplant (auto) for myeloma with 55.4% having one auto, 21% two autos, 5.1% three autos and 1.3% four autos. With respect to the number of lines of myeloma therapy prior to transplant; 1 line (29.4%), 2 (30.9%), 3 (16.9%), 4 (8.8%) and >4 (14%). 120 patients received chemotherapy for myeloma prior to their t-MN diagnosis, however data was missing in the remainder of patients in this study. Data on myeloma recurrence was available in 31.2% (49 patients), at 12- and 60 months myeloma recurrence was 4% and 12% respectively with myeloma NRM at 12- and 60 months 33% and 57%.

Univariate analysis failed to show any statistically significant difference in outcomes with respect to t-MDS vs t-AML, t-MN disease status, Karnofsky performance status, conditioning or donor source. Multivariate analysis was not possible due to the small numbers within this study. Further analysis of this data will be undertaken.

Conclusion

This study indicates that allo-HCT for t-MN following treatment for myeloma is a viable treatment option. The myeloma recurrence in this study was low and further strategies to reduce t-MN relapse and NRM are needed.

References;

1. Bhatia R, Deeg HJ. Treatment-Related Myelodysplastic Syndrome - Molecular Characteristics and Therapy. Curr Opin Hematol.2011;18(2):77-82.

Lawless:BMS Celgene: Speakers Bureau; Janssen: Speakers Bureau. Kröger:Takeda: Consultancy, Honoraria; Sanofi: Honoraria; Kite: Honoraria; Neovii: Honoraria, Research Funding; Riemser: Research Funding; DKMS: Research Funding; Amgen: Honoraria; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz: Honoraria. Platzbecker:Novartis: Honoraria; Takeda: Honoraria; Abbvie: Honoraria; Jazz: Honoraria; BMS/Celgene: Honoraria; Janssen: Honoraria; Silence Therapeutics: Honoraria; Geron: Honoraria. Brossart:MSD: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Finke:Riemser Pharma: Research Funding. Kuball:Miltenyi Biotech: Patents & Royalties: novel CAR T and engineering isolation strategies, Research Funding; GADETA: Current equity holder in private company, Patents & Royalties: on gdTCR engineering strategies and targets , Research Funding; Novartis: Research Funding. Nicholson:Amgen: Other: Travel grant; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Meeting grant. Drozd-Sokolowska:Sanofi: Honoraria; Janssen: Honoraria; AbbVie: Honoraria, Speakers Bureau; Servier: Honoraria, Speakers Bureau; Roche: Consultancy. Scheid:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. McLornan:CELGENE BMS: Research Funding, Speakers Bureau; ABBVIE: Speakers Bureau; NOVARTIS: Honoraria, Research Funding, Speakers Bureau; JAZZ: Honoraria, Speakers Bureau. Robin:MEDAC, ASTEX: Research Funding. Yakoub-Agha:Bristol Myers Squibb: Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support.