Second Autologous Stem Cell Transplant- an Effective Therapy for Relapsed Multiple Myeloma

Second Autologous stem cell transplant- An effective therapy for relapsed multiple myeloma with chemosensitive disease

Kamal Abbi, MD¹, Sean Devlin, PhD¹, Sergio Giralt, MD¹, Heather Landau, MD¹

¹Memorial Sloan-Kettering Cancer Center, New York, NY;

Background:  Therapeutic options for patients with Multiple myeloma (MM) whose disease has relapsed after a prior autologous stem cell transplant (SCT) include an expanding armamentarium of novel agents, often combined with traditional chemotherapy, or a second SCT, with no clear standard of care.  Methods:  We retrospectively analyzed the outcomes of patients who underwent salvage melphalan-based SCT for relapsed MM at Memorial Sloan-Kettering Cancer Center. Results: Between 1995 and 2012, 75 patients with MM received an initial SCT and then second autograft for relapsed disease at our center.  Conditioning was with melphalan 200mg/m2 (N=43), 180mg/m2 (N=1), 140mg/m2 (N=22), 100mg/m2 (N=9). The median age at 2^nd SCT was 59 years (range 36-75) and 58% (N=35) were male.  Of those with available data, 35% had high risk cytogenetics (including t (4;14), +1q, p53 loss or del 13q by karyotype) at the time of second SCT.  Median interval between first and salvage SCT was 38 months (range 7 -113).  Of 71 evaluable patients, 73% had chemotherapy sensitive disease prior to salvage SCT and 27% were chemoresistant.  Response was assessed at 2-3 mos post-SCT and 84% of evaluable patients achieved >= partial response (PR), 10% had stable disease (SD), and 7% progressed despite salvage SCT.  Following salvage SCT, 37 patients received maintenance therapy and 15 went on to allogeneic SCT.  The median PFS following second autograft was 10.1 mos (95% CI: 7.9-13.6); the median OS was 24 mos (95% CI: 19.5 – 50.5). Patients with chemosensitive relapse had better progression free survival (HR-0.51, CI: 0.22-0.77, P = 0.005) and overall survival (HR=0.37, CI- 0.19-0.70, P = 0.002) than patients with resistant relapse.  Those with high-risk cytogenetics at the time of second SCT had higher risk of death (HR 2.12, 95% CI: 1.03- 4.38, P = 0.04) compared to patients with standard risk cytogenetics. Conclusions:  Salvage SCT is an effective strategy for relapsed MM with chemosensitive disease and results in comparable PFS and OS to other salvage strategies.  With the FDA approval of multiple novel effective therapies, more relapsed patients will likely achieve measurable responses and should be evaluated for second stem cell transplant.  Incorporation of novel conditioning regimens and/or effective maintenance strategies may further improve outcomes with this approach