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Multiple myeloma; Autologous stem cell transplantation; Refractory myeloma; Progression-free survival; Overall survival; High-dose chemotherapy; Response rates; Retrospective analysis; Hematologic malignancy; Salvage therapy

Introduction

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by complex genetic alterations, bone marrow infiltration, and systemic organ damage. While the introduction of novel agents—such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies—has significantly improved outcomes, a subset of patients progresses to a refractory disease state, defined by resistance to at least two major drug classes. This stage presents a critical therapeutic challenge, as prognosis is generally poor and options are limited [1-5]. Autologous stem cell transplantation (ASCT) has remained a cornerstone in the management of eligible MM patients, especially in newly diagnosed cases. However, its role in refractory multiple myeloma (RMM)—especially after failure of multiple lines of therapy—remains under debate. This retrospective cohort analysis explores the efficacy and safety of ASCT in patients with refractory MM, using real-world data to evaluate survival outcomes and treatment response [6-10].

Discussion

This analysis reviewed the medical records of 176 patients with refractory MM who underwent ASCT between 2012 and 2021 across four tertiary cancer centers. All patients met eligibility criteria based on performance status (ECOG ≤2), organ function, and previous exposure to at least one proteasome inhibitor and one immunomodulatory agent. The majority of patients (61%) had triple-class exposed disease, while 39% had dual-class refractory disease. Median age at transplant was 59 years, and median time from diagnosis to ASCT was 32 months.

Pre-transplant induction regimens included carfilzomib-based triplets (44%), daratumumab-based regimens (28%), and pomalidomide-dexamethasone combinations (18%). Stem cell mobilization was achieved using cyclophosphamide and G-CSF, and high-dose melphalan (200 mg/m²) was administered for conditioning in most patients.

Post-ASCT outcomes showed a median progression-free survival (PFS) of 11.6 months and a median overall survival (OS) of 27.8 months. Importantly, 58% of patients achieved a very good partial response (VGPR) or better, while 21% achieved complete response (CR). These rates were notably higher in patients who responded to salvage therapy pre-ASCT, emphasizing the importance of disease control prior to transplant.

Patients with high-risk cytogenetics (del17p, t(4;14)) had a significantly shorter median PFS of 8.2 months, compared to 14.5 months in standard-risk patients (p<0.01). However, OS was not significantly different, suggesting that ASCT still offered meaningful disease control even in high-risk groups.

Transplant-related mortality (TRM) at day 100 was low at 2.3%, with most complications related to neutropenic sepsis. Non-hematologic toxicities included mucositis (42%), febrile neutropenia (38%), and gastrointestinal complications (18%). No secondary malignancies were observed within the follow-up period.

Maintenance therapy post-ASCT was administered in 61% of patients, most commonly with lenalidomide or ixazomib, and was associated with improved PFS in multivariate analysis. A smaller subset received consolidation therapy, which showed a trend toward deeper response, but did not reach statistical significance due to sample size.

While newer cellular therapies such as CAR-T and bispecific T-cell engagers are emerging in this space, ASCT remains accessible, cost-effective, and feasible even in heavily pretreated patients, especially in regions where advanced therapies are not readily available.

Conclusion

Autologous stem cell transplantation offers a viable and beneficial option for selected patients with refractory multiple myeloma, achieving meaningful response rates, manageable toxicity, and extended survival even in the context of heavily pretreated disease. Although its efficacy may be limited in ultra-refractory or high-risk cytogenetic subgroups, ASCT remains a critical bridge therapy in the modern era of myeloma management. Future research should explore integration of ASCT with immunotherapies, maintenance strategies, and precision-based risk stratification to further enhance its role in this challenging patient population.

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