Allogeneic Stem Cell Transplantation for Multiple Myeloma: A 34-Year Experience
Authors: Venegas Courtney , Lunning Matthew A. , Al-Kadhimi Zaid S. , Bhatt Vijaya R. , Lyden Elizabeth R. , Schmit-Pokorny Kimberly , Armitage James O. , Vose Julie M. , Holstein Sarah A. , Baljevic Muhamed 
Published: October 2019

Abstract
Background: Multiple myeloma (MM) accounts for slightly more than 10% of the hematologic malignancies in the United States, and is a cancer with rising incidence and prevalence globally. Unfortunately, almost all MM patients (pts) experience disease relapse and/or progression, requiring further salvage therapy. Patients who harbor high risk disease are particularly vulnerable, and require innovative treatment approaches. While the role of autologous stem cell transplantation (ASCT) in MM has been extensively studied over the decades, the utility of allogeneic stem cell transplantation (AlloSCT) in MM is not clearly defined. According to the current standards, it is reserved for high risk, multiply relapsed and/or refractory (rr) pts, and in some pt series, carries a long term survival rate (20% at 12 years, Mir et al. Clin Lymphoma Myeloma Leuk. 2015). Until the completion of ongoing prospective clinical trials, the role of AlloSCT in MM will remain based on the experience from multiple retrospective case series in various stages of disease. Nevertheless, it is likely to change further in an era of proteasome inhibitor (PI), immunomodulatory drug (IMiD), and other immune-based anti-MM therapies.
Methods: We have retrospectively reviewed a total of 29 pts who received AlloSCT since 1983 until 2017 at the University of Nebraska Medical Center (UNMC).
Results: Median age for all pts at AlloSCT was 48 (range, 37-64 years), 27 (93%) of the pts were Caucasian, and 18 (62%) were male. Of the 22 (76%) pts with available cytogenetic and/or fluorescence in situ hybridization information, 5 (23%) had high risk disease: 4 (18%) with del(17p) and 1 (5%) with t(14;16). Of the 23 (79%) pts with the available information for the international staging system (ISS), 7 (30%) had stages I and II each, while the remaining 9 (39%) had stage III disease. Median time from MM diagnosis to AlloSCT was 15 months (range, 5-67) and median number of prior lines of therapy was 2 (range, 1-7). In 27 (93%) pts with available information, 8 (30%) received prior PI-based, 4 (15%) prior IMiD-based, and 27 (100%) prior alkylator-based therapy. Seven (24%) pts had a prior ASCT while 1 (3.4%) had a prior AlloSCT. Thirteen (45%) had received previous radiation therapy. Out of 27 (93%) with available pre-AlloSCT treatment information, 5 (19%) pts underwent AlloSCT following a single line of induction therapy, while 22 (81%) received AlloSCT for rr MM after further salvage therapy. Only 8 (28%) received AlloSCT after the year 2004, while 21 (72%) received it prior to 2004. Sixteen (55%) of pts had residual MM at the time of AlloSCT, and disease status prior to AlloSCT was 13 (45%) with complete response (CR), 1 (3.4%) with very good partial response, 11 (38%) with partial response (PR), 1 (3.4%) with stable disease, and 3 (10%) with progressive disease (PD). Treatment response for the 20 (69%) evaluable pts at day 100 showed 16 (80%) with CR, 3 (15%) with PR and 1 (5%) with PD. Of 26 (90%) pts with available information, only 2 (8%) received maintenance therapy post-AlloSCT: 1 (4%) with pomalidomide and 1 (4%) with daratumumab. The treatment related mortality (TRM) was 31% at day 100. Acute graft versus host disease and chronic graft versus host disease (cGVHD) developed in 59% of pts for each. Median progression free survival was 11.3 months and median overall survival (OS) from the time of diagnosis and AlloSCT were 24 and 14.1 months (Figure 1.), respectively. Long term OS at and beyond 8 years of follow up was ~20%. A univariate analysis did not show any difference in OS by the type of graft received, peripheral blood (n=18, 62%) versus (vs) bone marrow (n=11, 38%), graft source, matched related donor (n=24, 83%) vs matched unrelated donor (n=5, 17%), and >1 vs 1 prior lines of therapy. However, the type of conditioning received, myeloablative (n=19, 69%) vs non-myeloablative (n=10, 34%), ISS stage I vs III, the presence of cGVHD, and 3 vs >3 prior lines of therapy trended toward significance with p<0.06 for each as predictors of survival. A multivariate analysis of all factors analyzed only showed ISS stage III vs stage I as a predictor of OS (p=0.0163).
Conclusion: More than 3 decades of UNMC experience with AlloSCT in MM suggests that it can be effective for a subset of pts, with long-term OS observed in 20% of the pts. Both TRM and disease relapse continue to be major culprits of poor outcome in other pts.

Disclosures
Lunning: Celgene: Consultancy; AbbVie: Consultancy; Astra-Zeneca: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Genzyme: Consultancy; Genentech: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Juno: Consultancy; Kite: Consultancy; Portola: Consultancy; Seattle Genetics: Consultancy; Spectrum: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy. Bhatt:CSL Behring: Consultancy; Incyte: Research Funding; Pfizer: Consultancy. Vose:Abbvie: Honoraria; Kite Pharma: Research Funding; Roche: Honoraria; Bristol Myers Squibb: Research Funding; Novartis: Honoraria, Research Funding; Legend Pharmaceuticals: Honoraria; Merck Sharp & Dohme Corp.: Research Funding; Acerta Pharma: Research Funding; Seattle Genetics, Inc.: Research Funding; Epizyme: Honoraria; Celgene: Research Funding; Incyte Corp.: Research Funding. Holstein:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.