Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost

Background Autologous hematopoietic stem cell transplant (ASCT) remains a cornerstone of therapy for eligible patients with multiple myeloma (MM) and can be incorporated as part of the initial therapy (early ASCT) or at the time of first relapse (delayed ASCT) [1]. Current guidelines recommend that adequate hematopoietic stem cells (HSC should be collected for a potential second ASCT, with a minimum goal of 2 million CD34+ cells/kg per transplant [2]. The stored HSC may be used for either a planned tandem transplant or future salvage ASCT. Less commonly, the previously stored HSC may be used for stem cell "boosts” following either dose intensive, non-myeloablative chemotherapy or for patients with "burned out” bone marrows secondary to extensive prior therapies. [3].

To our knowledge, there is a paucity of data on the effectiveness and survival outcome of patients with multiple relapsed MM who receive a stem cell boost following dose intensive chemotherapy. This study analyzes the clinical outcomes of multiply relapsed MM patients receiving multi-agent chemotherapy followed by a stem cell boost. Outcomes evaluated were overall response rate, proportion of patients who received a subsequent line of therapy, and overall survival.

Methods This is a retrospective chart review performed at 2 institutions (Hackensack University Medical Center and MedStar Georgetown University Hospital). Fifty-nine (59) patients with MM aged ≥18 years old who underwent first ASCT from 1999 to 2021 and who collected sufficient s to allow for either tandem or salvage transplant or potential future stem cell boost were included in this study. Response to therapy was defined as stable disease or better on evaluation 1 month following stem cell boost. Patients who received another line of therapy less than 1 month post boost but did not have evidence of disease progression at that time, were excluded from ORR analysis. Overall survival (OS) was defined as the time from stem cell boost to date of death or last follow up. Statistical analysis was performed using STATA v16.0 (Stata Corp, TX, USA). Survival analysis was carried out using the Kaplan-Meier method and the log-rank test was used to compare survival curves.

Results The patient characteristics who received a stem cell boost are shown in Table 1 (n=59): male gender (61 %), median age at diagnosis was 60 (range 37-81), median number of lines of therapy 6.3 5 Range 1-16). The patient who received only 1 prior line of therapy had aggressive relapse less than 100 days post melphalan-conditioned ASCT which necessitated use of urgent dose intensive chemotherapy. The stem cell dose used for the boost ASCT ranged from 0.4 to 9.8 X 10^6 CD34+ cells/kg (median 2.3). 1.6. Of the 49 evaluable patients, 28 (57.1%) had response to therapy 1 month post stem cell boost. Overall, 37 (62.7%) patients successfully received a subsequent line of therapy post stem cell boost. The median overall survival for the entire cohort was 129 days (range 1 - 1462 days) (Figure 1). OS was significantly longer in responding patients compared to those who did not respond (182 days vs 82 days, p=0.0081).

Conclusions Dose intensive, non-myeloablative chemotherapy can improve survival in heavily pretreated, usually penta-refractory MM that require disease for refractory relapse. The administration of a stem cell boost utilizing previously collected HSCs may assist with hematopoietic recovery following dose intensive chemotherapy and in this subset of patients who have poor marrow reserve from prior therapy. This study serves to demonstrate the clinical outcomes of patients treated with multiagent chemotherapy followed by a stem cell boost. With an ORR of 57.1%, this approach can be effective in the appropriate clinical setting and significantly improves OS in patients who do respond to therapy (Figure 2). The goal of such therapy is to achieve disease control, and often serves as a "bridge” for patients to receive subsequent myeloma-directed therapy that may not be readily available at the time of relapse, such as clinical trial or chimeric antigen receptor T-cell (CAR-T) therapy. This data allows for treating oncologists to appropriately implement and inform patients of the therapeutic uses and clinical outcomes of treating such patients with dose intensive multiagent chemotherapy followed by a stem cell boost.

Siegel:GSK: Honoraria, Speakers Bureau; Merck: Honoraria; Janssen: Honoraria; Celularity: Membership on an entity's Board of Directors or advisory committees; COTA: Current equity holder in private company, Current holder of stock options in a privately-held company; BMS: Honoraria, Speakers Bureau; Takeda: Honoraria. Parmar:Janssen: Consultancy, Honoraria. Biran:Amgen, Janssen, Karyopharm, Merck, BMS, Sanofi: Consultancy, Research Funding.