Stem Cell Mobilization and Autograft Purity with Novel Induction Regimens in Multiple Myeloma

Abstract

Background High-dose chemotherapy and autologous stem cell transplantation (ASCT) remains the standard-of-care in transplant-eligible patients with multiple myeloma (MM). Bortezomib with lenalidomide and dexamethasone (RVD) is the most common triplet induction regimen for patients with newly diagnosed MM in the US. Carfilzomib with lenalidomide and dexamethasone (KRD), however, has shown promising efficacy and may ultimately supplant RVD. Comparative studies of stem cell collection yields and autograft purity after RVD vs KRD induction have not been performed and merit investigation. Methods Study subjects received RVD or KRD induction therapy at Memorial Sloan Kettering Cancer Center between 2014-2018. Statistical analyses included unpaired t-test, chi-square test, ANOVA, and Fisher's exact test (P value Results Demographics were similar for the 2 cohorts (RVD: 126 patients, KRD: 101 patients) (Fig 1A). Deeper responses (VGPR or better), including bone marrow (BM) minimal residual disease (MRD) negativity by 10-color flow cytometry, were higher with KRD (Fig 1B). Pre-collection BM cellularity, interval from end of induction therapy to start of stem cell collection, and method of stem cell mobilization were similar for the 2 cohorts (Fig 2). Average time to stem cell collection completion (collection target = 10 × 106 CD34+ cells/kg) was slightly greater with KRD (RVD 1.87 vs KRD 2.2 days), as was the fraction of patients requiring ≥3 days to complete collection (RVD 21.4% vs KRD 39.6%) (Fig 2). Viable CD34+ cell content (cells/mcL) was significantly higher with RVD (111.31 vs 63.54, p=0.0019), which associated with higher total stem cell yield after RVD (RVD 11.21 × 106 vs KRD 9.44 × 106, p=0.0245). Collection failure was rare but higher with KRD (4 patients, 3.96%) than with RVD (1 patient, 0.8%) (p=0.17). Advanced age (≥70) was a common factor predictive of lower stem cell yields for both cohorts ( Conclusion KRD induces deeper clinical responses and greater stem cell graft purity than RVD without compromising stem cell yield or post-transplant engraftment kinetics, despite decreased viable CD34+ content of autografts and lower stem cell collection totals.