Deepening Responses after Upfront Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction Therapy

Abstract

High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Achievement of complete response (CR) and minimal residual disease (MRD) negativity are associated with improved progression-free survival (PFS) and overall survival (OS). With superior triplet- and quadruplet-based induction regimens, a higher proportion of patients are achieving deep responses of at least a very good partial response (VGPR) or better. The probability of achieving different levels of deeper hematologic responses post-ASCT based on the pre-ASCT depth of response is less clear in the existing literature but would be of value to patients and providers in discussing the added benefit of ASCT. We assessed the rate of deepening the hematologic response with upfront ASCT in patients with NDMM, mainly to MRD-negative CR, based on the response achieved after induction therapy. We retrospectively reviewed 210 patients with NDMM who underwent upfront ASCT at Mayo Clinic Rochester between May 1, 2018, and July 31, 2019. In addition to the availability of next-generation flow cytometry (NGF) testing for MRD status, which yielded a sensitivity of 10^-5, the more sensitive mass spectrometry-based assessment of peripheral blood (ie, MASS-FIX) for monoclonal proteins was used rather than conventional immunofixation. Pre-ASCT, 23 patients (11%) achieved MRD-negative CR, which increased to 66 patients (31%) post-ASCT. Of 187 patients not in MRD-negative CR pre-ASCT, 45 (24%) converted to MRD-negative CR. Patients with MRD-positive CR before ASCT had the highest rates of conversion to MRD-negative CR. HR cytogenetics did not impact rates of MRD-negative CR achievement post-ASCT irrespective of pre-ASCT IMWG response (P = 1.0). Overall, irrespective of IMWG response, 43 patients (20%) were MRD-negative pre-ASCT (19 in VGPR, 24 in CR or sCR), and 102 patients (49%) were MRD-negative post-ASCT (36 in VGPR, 66 in CR or sCR). Among 85 patients with VGPR post-ASCT, 36 achieved MRD negativity, of whom 8 (22%) progressed, whereas 49 had MRD-positive disease, of whom 24 (49%) progressed (P = .014). Upfront ASCT in patients with NDMM led to deeper responses, with 24% converting to MRD negative CR and more than doubling of the total rate of MRD negativity irrespective of IMWG response depth.

Keywords: Autologous stem cell transplantation; MASS-FIX; Minimal residual disease; Multiple myeloma.