Allogeneic Stem Cell Transplantation for High-Risk Multiple Myeloma

Introduction:

Autologous transplantation (ASCT) has been the standard for transplant-eligible multiple myeloma (MM) patients. However, allogeneic transplants (AlloT) can induce a graft-versus-myeloma effect, potentially leading to long-term survival or cure in patients with MM refractory to initial therapies. This analysis evaluates the survival outcomes of a small cohort of MM patients who underwent AlloT at a single institution.

Methods: A retrospective review was performed with IRB approval of all patients diagnosed with multiple myeloma who underwent AlloT at a single institution (Georgia Cancer Center, Augusta, GA) from 2000 to 2024. Patient data was collected from the institution's electronic medical records. Overall survival (OS) was estimated using the Kaplan-Meier method. OS was calculated as time from AlloT to death from any cause.

Results: From 2003 to 2010, eight patients received AlloT, comprising six males and two females. The median age at diagnosis was 51 years (35.7 - 72.4), and the median age at transplant was 52.5 years (36.4 - 72.8). Four patients were Caucasian, three were African American, and one was Asian. 5 patients were classified as Stage II refractory/relapsed MM and 3 patients were classified as Stage IIIA refractory/relapsed MM. 6 patients had undergone previous autologous transplant and showed continued disease progression prior to obtaining allogeneic transplant. 7 patients received allogeneic transplant from HLA-matched sibling, and 1 patient received a synergistic transplant from an identical twin. For initial therapy, one patient each received VAD, DT-PACE, VTD-PACE, and VelDex, while four received LenDex. For conditioning, three patients had BuCy, four had FluCy, and one had HDM. No patients had high risk cytogenetics. The median time to AlloT from diagnosis was 0.92 years. The median overall survival (OS) was 6.7 years (range: 1.8-20.1 years), with 75% and 62.5% alive at 2 and 5 years, respectively. For the four RIC patients, OS was 50% at 2 years and 50% at 5 years, while for myeloablative therapy OS was 100% at 2 years and 75% at 5 years.

Two patients had mild acute graft vs. host disease (GVHD), while five patients experienced chronic grade I GVHD of the skin, liver, and/or bowel, which all improved and were stable with immunosuppressive therapy. One patient showed no signs of GVHD but had an exacerbation of GVTE, leading to death.

Following AlloT, seven patients entered partial remission (PR). Five of those patients relapsed and one patient died shortly after transplant. Of the two non-relapse patients, one died due to complications of immunosuppressive therapy and one had minimally residual disease (MRD) but transferred care. Of the five patients who relapsed median time to relapse was 3.64 years (0.21-9.33). One patient did not receive further treatment, one patient received MPR (4 cycles), KD (6 cycles), and pomalidomide (1 cycle) after transplant following locally recurrent disease and achieved complete remission (CR) with MRD negative disease.One patient received CyBorD-R (11 cycles), then GMCSF, and eventually thalidomide followed by maintenance lenalidomide with the patient achieving PR with MRD. Another patient received lenalidomide, then began salvage treatment with DaraDex and then lenalidomide as maintenance and eventually achieved CR. The fourth patient had persistently progressive disease treated with CyborD, then Velcade, then CTD (2 cycles), and finally PAN-VelDex and eventually entered palliative care. In total, seven of the eight patients have died and one has been lost due to transfer. Time to death following transplant was a median of 7.89 years (0.37 - 17.6).

Conclusion: Allogeneic transplantation (AlloT) for multiple myeloma (MM) has traditionally been fraught with challenges, particularly due to the associated toxicity. Despite this, allogeneic transplantation remains a viable salvage option for relapsed/refractory multiple myeloma patients, with possible use cases following a poor response to ASCT. Optimization of initial therapy/conditioning regimens continues to be a difficult aspect of management, and future studies can continue to evaluate the role of nonmyeloablative regimens and their effectiveness. Future studies should focus on utilizing AlloT as a salvage option to better understand its role and potential benefits in managing advanced (Stage II/III), refractory MM patients.

Kota:Pfizer: Honoraria; Novartis: Honoraria; Kite Pharma: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sun Pharma: Consultancy, Research Funding; Abbvie: Research Funding; Biopath Holdings: Consultancy, Research Funding; Takeda: Consultancy; Nerviano: Consultancy; Rigel: Consultancy.