The Role of High Dose Chemotherapy and Autologous Stem Cell Transplantation In Patients with Multiple Myeloma Refractory to Initial Induction Therapy
Authors: Parrish Christopher , Rahemtulla Amin , Cavet James , Pearce Rachel , Keiran Kirkland , Lee Julia , Craddock Charles , Wilson Keith , Cook Gordon 
Published: October 2019

Abstract
Abstract 1341

Rationale:
Studies to date clearly demonstrate that patients with multiple myeloma (MM) who receive induction chemotherapy consolidated with high-dose therapy (HDT) and peripheral blood autologous stem cell transplant rescue (ASCT) have increased event-free survival (PFS) and overall survival (OS) compared to those receiving conventional chemotherapy. Maximal benefit is seen in patients who ≥ very good partial response (VGPR) following induction therapy and ASCT. However, nearly one third of patients with newly diagnosed MM fail to achieve a partial response (PR) after initial therapy and though novel therapies induce better up-front response rates, failure to achieve at least a PR is still evident in up to 20% of patients. Therefore we sought to delineate the clinical course of patients who underwent ASCT with <PR following induction therapy for MM to determine prognostic factors associated with better outcomes.

Methods:
Eligible patients were identified from the British Society of Blood and Marrow Transplantation (BSBMT) Data Registry and additional patient-specific data were acquired directly from individual centres. Patients were eligible if, after induction therapy, they demonstrated minimal response (MR), stable disease (SD) or progressive disease (PD), as defined by International Myeloma Working Group criteria. All patients received ASCT and disease response was assessed at day 100 (D+100) post-transplant.

Results:
228 eligible patients transplanted in 2000-08 were identified with a median age at transplant of 57 yrs (range 33–72). Patients had received between 1 and 7 prior therapies, and at the time of transplant 70 patients (31%) had obtained MR, 80 (35%) had SD and 77 (34%) had PD. Median time from diagnosis to transplant was 10 months (95% confidence intervals (CI) 9, 10). Median beta-2 microglobulin at diagnosis was 3.5 (range 1.1, 76), serum albumin 36 (range 13, 49), serum creatinine at ASCT 88.5 (range 43, 864). Responses to ASCT (D+100): 49/207 (24%) patients in complete response (CR), 6/207 (3%) in VGPR, 54/207 (26%) in PR, 2/207 (1%) in MR, 10/207 (5%) in SD and 3/207 (1%) had PD with 21 not evaluable for response (due to early death n=13). Non-relapse mortality (NRM) at 100 days, 1 year and 5 years was 2%, 3% and 10% respectively. By univariate analysis (UVA), albumin at diagnosis (p=0.007) impacted on NRM with a trend associated with male sex (p=0.07) and by multivariate analysis (MVA), only albumin at diagnosis (p=0.006) was an independent factor. The relapse rates at 1 year and 5 years were 29% and 79% respectively, with status at transplant (p=0.0004) the only significant variable on UVA. Progression-free survival (PFS) at 5 years was 13% with a median PFS of 18 months (95% CI 15, 21). On UVA, albumin at diagnosis (p=0.025), disease status at transplant (p=0.00003), time from diagnosis to transplant (p=0.027 for < or > 9mns; p<0.00022 for continuous analysis) significantly affect the PFS and on MVA, disease status at (p=0.022) and albumin at diagnosis (p=0.026) were independent prognostic factors. OS at 5 years was 41%, with a median of 51 months (95% CI 45,61) On UVA, disease status (p=0.00015) and time from diagnosis to transplant (p=0.0029, continuous) were significant with a trend noted for albumin at diagnosis (p=0.061) and on MVA only status at transplant (p=0.031) significantly affected OS.

Conclusion:
HDT followed by ASCT in patients failing to achieve at least a PR after induction therapy provides an effective means of inducing a deeper remission, which despite demonstrating a shorter median PFS than those transplanted in >PR, demonstrate a good 5 yr OS in an otherwise difficult-to-manage group of patients. This is likely to be reflective of advances in salvage therapy utilized at relapse.

Disclosures:
No relevant conflicts of interest to declare.