Outcomes Following Salvage Autologous Stem Cell Transplant for Multiple Myeloma

High-dose therapy and stem cell transplant (SCT) has improved the progression-free and overall survival of patients with MM. However all patients eventually develop disease recurrence. In the era of effective novel agents (such as bortezomib, lenalidomide and thalidomide), the optimal salvage strategy is undefined.

We retrospectively analyzed the outcomes of patients who underwent salvage melphalan-based SCT for relapsed MM at Memorial Sloan-Kettering Cancer Center.

Between 1995 and 2010, 53 patients with MM received a second autograft for relapsed disease at our center. Conditioning was with melphalan 100 (N=8), 140 (N=18) or 200mg/m2 (N=27). The median age at 2^nd SCT was 60 years (range 36–75) and 62% (N=33) were male. Twenty-three percent (N=12) had high risk cytogenetics (including t(4;14), +1q, p53 loss, or del 13q by karyotype) while 77% had standard risk or cytogenetic studies were not available. The median interval between SCTs was 34 mos (range 6.2–88.7). Of evaluable patients, 79% (37/47) had chemotherapy sensitive disease prior to salvage SCT and 21% were chemoresistant. Response was assessed at 2–3 mos post-SCT and 70% of evaluable patients achieved >= partial response (PR), 17% had stable disease (SD), and 13% progressed despite salvage SCT. Following salvage SCT, 6 patients received maintenance therapy and 7 went on to allogeneic SCT. The median progression-free survival (PFS) following second autograft was 13.1 mos (95% CI: 10.1–18.4). Patients with high-risk cytogenetics at the time of second SCT had higher risk of progression (HR 2.5, 95% CI: 1.15–5.24, P = 0.02) compared to patients who had standard risk cytogenetics. However, interval from first to second SCT, chemosensitivity, and response following second transplant had no significant impact on PFS. The median OS following salvage SCT was 24 mos (95% CI: 18 – 41) and was superior for patients with standard versus high risk cytogenetics (HR 3.51, 95% CI: 1.57–7.86, P = 0.002). Again, interval since prior SCT and response following salvage SCT did not impact survival. Chemosensitivity was associated with reduced risk of death (HR 0.42, 95% CI: 0.18–0.96, P = 0.04). Although the sample size was small, the OS was not significantly extended for patients who received maintenance therapy or allogeneic SCT following salvage autologous SCT.

Salvage SCT is an effective strategy for relapsed MM following initial autograft and results in responses in the majority of patients. Although OS and PFS following salvage SCT is similar to other salvage strategies, novel conditioning regimens and/or effective maintenance strategies may improve this approach.

Comenzo:Millenium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Elan Pharmaceuticals: Consultancy; Genzyme: Research Funding; Celgene: Research Funding; Ortho: Research Funding.