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

BACKGROUND: High dose melphalan followed by autologous stem cell transplant (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 VGPR or better. The probability of achieving different levels of deeper hematological 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. OBJECTIVE: We assessed the rate of deepening the hematological response with upfront ASCT in patients with NDMM, mainly to MRD negative CR, based on the response achieved after induction therapy. STUDY DESIGN: We retrospectively reviewed 210 patients with NDMM who underwent upfront ASCT at Mayo Clinic Rochester from May 1st, 2018 to July 31st, 2019. In addition to the availability of next generation flow cytometry testing for MRD status, that yielded a sensitivity of 10-5, the more sensitive mass spectrometry-based assessment of peripheral blood (i.e., Mass-fixation) for monoclonal proteins was utilized rather than conventional immunofixation. RESULTS: Pre-ASCT, 23 patients (11%) achieved MRD negative CR which increased to 66 (31%) patients 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 (20%) patients were MRD negative pre-ASCT (19 in VGPR, 24 in CR or sCR) and 102 (49%) patients 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 which 8 (22%) progressed, while 49 had MRD positive disease of which 24 (49%) progressed (p = 0.014). CONCLUSION: Upfront ASCT in patients with NDMM leads 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.