INTRODUCTION With the advent of novel therapeutic agents, the management of relapsed multiple myeloma (MM) has shifted markedly, and the value of a second salvage autologous hematopoietic cell transplantation (AHCT2) remains contentious. Nevertheless, in many countries these innovative treatments are not yet accessible, leaving AHCT2 as a viable alternative. Accordingly, we performed a retrospective analysis of MM patients who underwent AHCT2 after first relapse in Latin American countries.

METHODS Retrospective analysis on previously transplanted patients with MM who underwent AHCT2 as consolidation following first relapse between 2003-2024, at thirteen transplant centers from Argentina, Chile, Mexico and Uruguay. The primary objective was to evaluate progression-free survival (PFS2) defined as the time from AHCT2 (infusion date) to the date of relapse, death, or last follow-up.

RESULTS One hundred forty-one patients were included: 62% IgG, 55% kappa light chain, 21% ISS III, 10% R-ISS III and 16% high-risk cytogenetics at diagnosis. Median time between the first and second AHCT was 61.0 months (IQR 47-76). At the time of AHCT2 the median age was 59 years (IQR 54–64) and the median of prior lines of therapy was 2 (range 2–5). Twelve patients (8%) had extramedullary involvement. Prior exposure to bortezomib, lenalidomide and daratumumab was 121 (86%), 70 (50%), and 24 (17%), respectively, while 33%, 16%, and 3% were refractory to immunomodulators, proteasome inhibitors, and anti-CD38 antibodies, respectively. Four patients were triple refractory.

All patients received conditioning with melphalan single-drug and cryopreserved grafts in 77 cases (55%). Stem cell mobilization occurred at the time of relapse in 92 % of cases. Disease status prior to AHCT2 was: complete response (CR) 31 (22%), very good partial response (VGPR) 38 (27%), partial response (PR) 53 (37%), stable disease (SD) 2 (2%), progressive disease (PD) 2 (2%), and unknown in 15 cases. At day +100 post AHCT2 response rates was: CR 52 (37%), VGPR 29 (21%), PR 32 (23%), and no cases of PD (unknown in 28 cases). Maintenance therapy after AHCT2 was administered in 80/98 patients (lenalidomide monotherapy 47/80). With a median follow-up after AHCT2 of 48 months (IQR 17-78), 4-year OS was 57.7% and 4-year PFS2 was 31.2%. Median PFS was 30.6 months (95%CI:23–36). Lenalidomide-refractory patients showed significantly shorter PFS2: 15.2 months (95%CI:11–26) vs 34.0 months (95%CI:25–41) in non-refractory patients (p=0.011). The median PFS2 was 9.9 months for patients with extramedullary disease at the time of AHCT2 versus 31.9 months for those without extramedullary involvement (p < 0.001). In the multivariate analysis, extramedullary disease at the time of AHCT2 (HR 2.53; p=0.006) and Len-refractory disease (HR 1.96; p=0.025) were independent predictors of PFS2. The following variables did not significantly impact PFS2 in the model: age, disease status prior to AHCT2, ISS, R-ISS, high-risk cytogenetics, number of prior lines and cryopreservation.

Seventy-six patients relapsed after AHCT2 with a 4-year cumulative incidence of relapse of 61%. Seventy-one patients died (52 due to progression, 9 unknown causes, 8 infections and 2 secondary malignancy) with a 3-month cumulative non-relapse mortality of 1.4%. Six patients developed secondary malignancy after AHCT2 (four solid tumor and two hematological malignancies).

CONCLUSION A second AHCT is a valid and safe consolidation strategy that achieved a PFS2 of more than 2.5 years and improved the quality of response. Collection of stem cells is feasible in this setting, thereby avoiding the need for long-term storage of cryopreserved stem cells. Len-refractory and extramedullary disease may obtain less benefit with AHCT2.

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2025
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