Second Autologous Stem Cell Transplant: An Effective Therapy for Relapsed Multiple Myeloma

Abstract

Therapeutic options for patients with multiple myeloma (MM) whose disease has relapsed after a prior autologous stem cell transplant (ASCT) include an expanding armamentarium of novel agents, often combined with traditional chemotherapy, or a second ASCT, with no clear standard of care. We retrospectively analyzed the outcomes of 75 patients who underwent salvage melphalan-based ASCT for relapsed MM at Memorial Sloan-Kettering Cancer Center between 1995 and 2012. Conditioning was performed with melphalan 200 mg/m(2) (n = 43), 180 mg/m(2) (n = 1), 140 mg/m(2) (n = 22), and 100 mg/m(2) (n = 9). The median age at second ASCT was 59 years (range, 36 to 75), and 58% (n = 35) were men. Of those with available data, 19% had high-risk cytogenetics (including t (4;14), p53 loss, or del 13q by karyotype) at the time of second ASCT. Median interval between first and salvage ASCT was 37.5 months (range, 6.9 to 111.4). Of 72 assessable patients, 57% had chemotherapy-sensitive disease before to salvage ASCT and 43% were chemoresistant. Four patients died within 100 days of ASCT. Response was assessed at 2 to 3 months post-ASCT, and of 71 assessable patients, 82% achieved at least a partial response, 15% had stable disease, and 3% progressed despite salvage ASCT. After salvage ASCT, 38 patients received maintenance therapy and 14 went on to allogeneic ASCT. The median progression-free survival (PFS) after second autograft was 10.1 months (95% confidence interval [CI], 7.6 to 13.4) and median overall survival (OS) 22.7 months (95% CI, 19.2 to 41.2). Patients with chemosensitive relapse had a trend toward better PFS (hazard ratio [HR], .60 [95% CI, .36 to 1.02]; P = .058) and significantly longer OS (HR, .49 [95% CI, .27 to .88]; P = .017) than patients with resistant relapse. Those with high-risk cytogenetics at the time of second ASCT had higher risk of death (HR, 2.98 [95% CI, 1.28 to 6.97]; P = .012) compared with patients with standard-risk cytogenetics. Salvage ASCT is an effective strategy for relapsed MM with chemosensitive disease and results in comparable PFS and OS to other salvage strategies.

Effect of melphalan 140 mg/m2 vs 200 mg/m2 on toxicities and outcomes in multiple myeloma patients undergoing single autologous stem cell transplantation—a single center experience

“…These three retrospective studies involved tandem transplants which makes drawing conclusions difficult in the non‐tandem transplant population. When used for second ASCT, MEL140 and MEL200 had similar progression free survival and OS …”

Outcome of allogeneic transplantation in newly diagnosed and relapsed/refractory multiple myeloma: long‐term follow‐up in a single institution

“…Although the overall survival of patients relapsing after 18 months is promising, the short PFS in this group suggests a poor graft‐vs.‐myeloma effect and the extended OS probably reflects effective relapse treatment after allo‐SCT with novel agents. For patients relapsing beyond 1.5‐2 yr after auto‐SCT, we generally recommend novel agent‐based therapy or, in case of transplant eligible patients, a second auto‐SCT .…”

The Role of Salvage Second Autologous Hematopoietic Cell Transplantation in Relapsed Multiple Myeloma

“…The optimal PFS following first ASCT for consideration for SAT varies in the literature from as short as 12 months [15,21] to as long as 36 months [11] to be predictive of a PFS advantage following SAT and from as short as 9 months [16] to as long as 36 months [11] to be predictive of an OS advantage (Table 1). Other studies have shown a linear relationship between increasing PFS following first ASCT and PFS and OS advantages following SAT [15,21,22]. The only exception to this trend was a recent study by Tremblay et al [23], in which PFS after first ASCT was not found to be predictive of PFS or OS following SAT.…”