Transplantation as salvage therapy for high-risk patients with myeloma in relapse

Abstract

Summary:Patients with myeloma relapsing after tandem transplant have a poor survival and treatment options are limited. The role of additional salvage transplant procedures for these patients is unknown. To evaluate the benefit and identify prognostic factors, the outcome of 76 consecutive patients with recurrent myeloma after tandem transplant receiving salvage transplants (ST) was analyzed. Prior to ST, 23 patients (30%) had shown chemosensitive response to preceding salvage chemotherapy: two complete remissions (CR); eight near CRs (nCR: only immunofixation positive); 13 partial remissions (PR у75% reduction in M protein). Fifty received an autologous transplant, 22 a sibling-matched allogeneic transplant, and four a matched-unrelated allogeneic transplant. Overall response after ST was 59%: eight CRs (11%); 14 nCRs (18%); 23 PRs (30%). Overall survival (OS) at 2 years was 19%; 2 year eventfree survival rate (EFS) 7%. On univariate analysis for survival, only pre-transplant chemosensitive relapse (P Ͻ 0.05), serum albumin Ͼ3 g/dl (P = 0.001), normal LDH (P = 0.04), and long interval between the second transplant and relapse/progression were significant beneficial factors. In a Cox proportional hazard model, chemosensitive relapse, and albumin Ͼ3 g/dl were significant for better OS: hazard ratio (HR) 1.4, 1.7, respectively, while normal LDH, and absence of CA13 were significant for better EFS: HR 1.8, 1.7, respectively. Patients with albumin Ͼ3 g/dl who had chemosensitive disease before ST (n = 16) had a median survival of 16 months, compared to 7 months (n = 34) and 2 months (n = 26) for patients with only one (n = 34) or no favorable prognostic factors (n = 28), respectively (P Ͻ 0.001). Their survival at 2 years post-ST was 43%, 17% and 11%, respectively. Our study suggests further transplantation should only be considered in the setting of a clinical trial in patients with favorable prognostic factors. Long-term myeloma control has become possible since high-dose therapy (HDT) with melphalan was introduced in the mid-1980s.1 Treatment-related mortality of HDT has decreased to less than 3% with autologous peripheral blood stem cell support and improved supportive care. 2,3 In newly diagnosed myeloma, about 40% of patients achieve CR, resulting in a significant increase in EFS and OS when compared to conventional therapy. [4][5][6] Further intensification of HDT by using tandem transplantation was apparently associated with progressive increase in CR rate and additional survival benefit.6 A recent randomized trial by IFM (IFM-94 02) showed significant improvement in both EFS and OS with tandem transplantation compared to a single transplant. This difference only became apparent after 42 months of follow-up.

Consensus statement from European experts on the diagnosis, management, and treatment of multiple myeloma: from standard therapy to novel approaches

“…Finally, a randomized trial comparing early versus late ASCT demonstrated improved PFS for earlier transplantation (39 months vs. 13 months), while OS was not significantly different. Early ASCT was also associated with an improved quality of life and higher remission rates, thought to arise because of the better performance status of the patients with early ASCT who were also less heavily pretreated [60][61][62][63][64][65][66][67][68][69][70] and thus less likely to have multi-drug resistant disease. Future studies will need to more clearly define the benefit of 'upfront' ASCT versus deferring the procedure, as current data suggest that the median OS with early versus delayed ASCT may be similar, bearing in mind, of course, that with later-scheduled ASCT, patients may never actually get to transplant.…”

Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma

“…To our knowledge, here is no standard salvage treatment for patients who develop disease recurrence after an autograft. Treatments ranging from conventional agents to salvage autologous and allogeneic transplants have been used 5–11…”

Stem cell mobilization in multiple myeloma patients: Do we need an age‐adjusted regimen for the elderly?

“…Also, some groups propose the transplantation of as many hematopoietic progenitor cells as possible leading to faster hematopoietic recovery and improved outcome [10]. Additionally, even after tandem transplantation, a third high-dose melphalan therapy can be of benefit in case of disease progression after a reasonable remission duration [25]. Therefore, a collection of progenitor cells in patients diagnosed with multiple myeloma should aim at enough cells for more than one transplant.…”