Outcomes of allogeneic hematopoietic stem cell transplantations (HSCT) for treatment of secondary primary malignancies arising post-autologous HSCT for multiple myeloma

Abstract

Abstract Secondary primary malignancies (SPMs) are a known complication of multiple myeloma (MM) and its treatment; resulting from baseline cell changes in MM, myeloma-specific therapies, and the autologous hematopoietic stem cell transplantations (Auto-HSCT) utilized as an attempt to induce a deep long-term remission. Strong associations exist with hematological SPMs, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In the event of hematological SPM development following Auto-HSCT, allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is often utilized. While there have been considerable efforts placed into studying the long-term outcomes of Auto-HSCT, as well as the associations of hematological SPM development with preceding treatment, there is a paucity of data on the outcomes of patients who undergo Allo-HSCT in this situation. We performed a single-institution retrospective review utilizing the Karmanos Cancer Institute (KCI) bone marrow transplant database. Any patients who received an Allo-HSCT for treatment of hematological SPM, which occurred following an initial Auto-HSCT for MM, was included. Data was summarized using count/percentage for categorical variables, and median/range for continuous variables. Kaplan–Meier estimates were used for overall survival (OS), relapse-free survival (RFS), and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). A total of 17 patients (9 females and 8 males) received Allo-HSCT under the above conditions from 2010 to 2024. The median age at the time of initial Auto-HSCT was 63 years (range 41-76). The median time to SPM development following Auto-HSCT was 1511 days (range 341-5294). The SPMs included 10 patients with MDS, 4 with B-ALL, and 3 with AML. Among those with MDS/AML, 6 patients had a complex karyotype. There were 8 patients with a TP53 mutation (4 with complex karyotype and 3 with deletion of 5q). The median age at Allo-HSCT was 67 years (range 48-77), and median Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score prior was 5 (range 1-11). Regarding SPM-specific induction chemotherapy regimens prior to Allo-HSCT, 14 received them and 3 did not. Status of SPM at the time of Allo-HSCT included 7 (41.2%) with complete response (CR), 2 (11.8%) with partial response (PR), and 8 (47.1%) with persistent disease (PD). All patients received peripheral blood stem cell transplants (PBSCT). Regarding HLA-matching status, 12 patients were fully HLA-matched (5 10/10-matched, 7 8/8-matched), 4 patients received 7/8 HLA-mismatched unrelated donor (MMUD) transplant, and 1 patient received haploidentical donor transplant. Of those with fully matched donors, 11 were a matched unrelated donor (MUD), and 1 from a matched related (MRD). As conditioning regimens, 12 patients received Fludarabine/Busulfan, and 5 patients received Fludarabine/Melphalan. Only 1 patient received a myeloablative regimen, the other 16 patients received reduced-intensity conditioning (RIC). For GVHD prophylaxis, 6 patients received Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil (MMF); 9 patients received Thymoglobulin, Tacrolimus, and MMF; 1 patient received Thymoglobulin, Sirolimus, and MMF; 1 patient received Tacrolimus, Methotrexate, and Abatacept. Our data demonstrates that 12-month OS and RFS were both 45.3% (95% CI, 26.5-77.5), and 12-month GRFS was 30.2% (95% CI, 13.8-65.9). There was a median follow up of 15.7 months (95% CI, 11.6-NE) among those still alive at time of analysis. At 100 days post-Allo-HSCT, cumulative incidence of aGVHD (grades II-IV) was 35.3% (95% CI, 13.8-57.8), and severe aGVHD (grades III-IV) was 23.5% (95% CI, 6.9-45.7). At 12 months, cumulative incidence of cGVHD was 35.6% (95% CI, 11.4-61.3), severe cGVHD was 21.0% (95% CI, 4.3-46.0), SPM relapse was 12.4% (95% CI, 1.8-33.6), and NRM was 42.4% (95% CI, 18.0-65.0). This single-institution retrospective analysis shows a 12-month OS and RFS of 45.3%, and a 12-month GRFS of 30.2%. Limitations of the outcome data include a relatively small population that underwent Allo-HCST, likely lower than the true number of patients with SPM following Auto-HSCT due to them either not returning to the center or opting against Allo-HSCT for treatment. This data adds to the collective understanding of the associated risks and benefits of Allo-HSCT for treatment of hematological SPM following Auto-HSCT for MM.