# Second Salvage Autologous Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Multiple Myeloma in the Era of Novel Agents: Results of the KMM2301 Study

## TL;DR

This study finds that a second stem cell transplant can still help some multiple myeloma patients if done early after relapse and when the first treatment was effective.

## Contribution

The study clarifies the clinical benefit of second salvage autologous stem cell transplantation in the era of novel agents for multiple myeloma.

## Key findings

- Patients with a long response after first transplantation and early SAT had better survival.
- SAT was associated with longer overall survival compared to drug-based regimens in selected patients.
- Later-line SAT was linked to worse outcomes, emphasizing the importance of timing.

## Abstract

Multiple myeloma is a blood cancer in which most patients eventually relapse after initial treatment, including a first autologous stem cell transplantation. Although many new drugs are now available, it remains unclear whether a second salvage autologous stem cell transplantation (SAT) still provides benefit in current clinical practice. In this study, we examined outcomes of patients who received SAT after relapse and compared them with patients treated with a commonly used drug-based salvage regimen without transplantation. We found that patients who had a long-lasting response after their first transplantation and who received an SAT early after relapse tended to have better survival outcomes. These results suggest that SAT may still be a useful treatment option for carefully selected patients, rather than a routine approach for all relapsed patients. This study helps to clarify when SAT may remain relevant in the era of effective modern therapies.

Background: Second salvage autologous stem cell transplantation (SAT) is a therapeutic option for patients with multiple myeloma (MM) who relapse after a first autologous stem cell transplantation (ASCT) in the era of novel agents. However, the clinical context in which SAT provides benefit relative to contemporary salvage regimens remains unclear. Methods: We retrospectively analyzed 51 patients who underwent SAT after novel agent-based induction and first ASCT, and salvage re-induction, and compared outcomes with 113 patients treated with salvage carfilzomib–lenalidomide–dexamethasone (KRd) without SAT. Results: Median interval from first ASCT to relapse was 27 months. In the SAT cohort, median progression-free survival (PFS) and overall survival (OS) from initiation of salvage therapy were 30 and 99 months, respectively. A time to relapse ≥18 months after first ASCT and receipt of SAT as second-line of therapy were associated with significantly longer PFS and OS. In multivariate analysis, administration of SAT at later lines was independently associated with inferior outcomes, while a time to relapse ≥18 months after first ASCT was associated with significantly longer OS. Compared with the KRd-only cohort, SAT was associated with longer OS, whereas PFS was numerically longer without statistical significance. Among patients who had received both a proteasome inhibitor and an immunomodulatory drug as salvage induction, SAT was associated with longer PFS and OS. Conclusions: SAT may provide clinical benefit in selected patients with MM, particularly those with a durable response to first ASCT and those undergoing SAT at an earlier line of relapse in the novel agent era.