Myeloma Patients Relapsing after First Line Treatment with Tandem Auto/Allo Transplant or Auto Transplant Only Have Similar Outcomes.

Abstract

<h3>Background</h3> A better survival in patients with multiple myeloma (MM) progressing after tandem autologous (auto)/allogeneic (allo) hematopoietic stem cell transplantation (HSCT) has been previously reported (Htut M. et al. BBMT 2018), suggesting a persistent graft-versus-multiple myeloma (GvMM) effect even after relapse. We sought to confirm this observation in a homogeneous cohort of MM patients who relapsed after upfront tandem auto/allo HSCT in our institution. <h3>Methods</h3> 92 consecutive, newly diagnosed MM patients who received tandem auto/allo HSCT were paired with 81 patients who received auto HSCT only between 2001 and 2010. Patients pairing criteria were age ≤ 65 years at diagnosis, Durie-Salmon 1B, 2 or 3, a glomerular filtration rate ≥ 60 mL/min, only one line of induction treatment, absence of progression within 4 months of auto HSCT and cytogenetics (if available). After their 1^st auto HSCT with high dose melphalan, all allo transplant recipients received an outpatient nonmyeloablative conditioning of fludarabine 30 mg/m² and cyclophosphamide 300 mg/m² × 5 days followed by G-CSF mobilized stem cells from a matched sibling donor. <h3>Results</h3> Median age in the auto/allo group was 53 years, compared to 57 years in the auto group (p<0.001). Both groups were similar for sex, immunoglobulin isotype, Durie-Salmon and ISS stages. With a median follow-up of 13.1 and 10.2 years (p<0.001), respectively, median overall survival (OS) in the tandem group has not been reached, compared to 6.1 years in the auto group only (p<0.001, Fig. 1). OS and PFS at 10 years in tandem and auto groups were 61% vs 37% (p<0.001) and 49% vs 22% (p<0.001), respectively. Disease progression occurred in 46 of 92 tandem recipients and 63 of 81 auto recipients, with an estimated 10-year cumulative incidence of progression (CIP) significantly lower in the tandem group (50% vs 77%; p<0.001, Fig. 2). Median OS at 10 years after 1^st progression was 39% in the tandem group and 22% in the auto group (p=0.062, Fig. 3). In multivariate analysis of factors associated with CIP, the only significant variable was tandem transplant (hazard ratio 0.44; 95% CI: 0.24-0.80, p=0.008), independently from age, ISS stage, type of induction and response before 1^st auto HSCT. Main cause of death was MM in both groups. <h3>Conclusion</h3> Tandem auto/allotransplant enables long-term survival and offers a potentially curative option in selected newly diagnosed MM patients. At time of 1^st relapse, tandem auto/allo transplant does not confer a significant outcome advantage compared to auto HSCT only.