Salvage or Second Autologous SCT in Relapsed Multiple Myeloma (2016–2026): A Decade in Review

TL;DR

This review finds that a second stem cell transplant can still be a safe and effective treatment for some patients with relapsed multiple myeloma, especially those who had a long initial remission.

Contribution

The paper provides an updated, evidence-based evaluation of second autologous stem cell transplants in the context of modern immunotherapies for multiple myeloma.

Findings

ASCT2 is feasible with low non-relapse mortality and offers improved outcomes for patients with prolonged remission after the first transplant.

Patients relapsing ≥24 months after the first transplant achieve the best progression-free and overall survival results.

ASCT2 should be used selectively and in combination with maintenance therapy or immunotherapies, not as a routine procedure.

Abstract

Multiple myeloma is a blood cancer that often returns after initial treatment, which can include a stem cell transplant. For these relapsed patients, a second transplant is a possible treatment, but its value is being re-evaluated as newer immune-based therapies become available. This review examines research from the past decade and confirms that a second transplant remains a safe and effective choice for carefully selected patients. The best results are seen in patients who had a long period of remission after their first transplant. Our findings suggest that a second transplant should be considered a personalized tool, used alongside other modern treatments, rather than a routine procedure for every relapsed patient. This highlights the need for studies directly comparing it to new immunotherapies.

Background: The role of second or salvage autologous stem cell transplantation (ASCT2) in relapsed multiple myeloma (MM) has evolved substantially over the past decade with the introduction of novel agents, maintenance strategies, and cellular immunotherapies. The clinical value of ASCT2 in the contemporary era requires reappraisal based on modern real-world and prospective data. Methods: We conducted a targeted literature review of PubMed-indexed studies published between January 2016 and January 2026 evaluating second or salvage autologous transplantation in adult patients with relapsed or refractory multiple myeloma. Retrospective registry analyses, real-world cohorts, and prospective randomized trials were included, focusing on feasibility, toxicity, progression-free survival (PFS), overall survival (OS), and prognostic determinants. Fourteen key studies formed the core evidence base, supplemented by guideline statements and comparative immunotherapy data. Results: Across large registry and institutional series, ASCT2 was consistently feasible with low non-relapse mortality (≤5% at day 100–1 year). The median PFS ranged from 9.8 to 30.2 months and the median OS from approximately 30 to >80 months, with outcomes strongly influenced by duration of remission after first ASCT. Patients relapsing ≥24 months after ASCT1 derived the greatest benefit, achieving a median PFS of 17–45 months and OS exceeding 60 months in favorable-risk subgroups. Post-ASCT2 maintenance, particularly with lenalidomide or carfilzomib-based regimens, significantly prolonged disease control in randomized and real-world studies. Conversely, the phase III GMMG ReLApsE trial did not demonstrate a survival advantage for routine salvage ASCT over continuous lenalidomide-based therapy, highlighting the importance of patient selection. In heavily refractory or cytopenic populations, ASCT2 provided modest disease control but enabled hematopoietic recovery and access to subsequent therapies. Conclusions: In the modern treatment landscape, second or salvage autologous transplantation remains a valid, safe, and effective strategy for carefully selected patients with relapsed multiple myeloma, particularly those with chemosensitive disease and prolonged initial remissions. ASCT2 should be integrated in a risk-adapted manner alongside maintenance therapy and emerging immunotherapies, serving as a durable consolidation or bridging approach rather than routine therapy for all relapsed patients.

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