Functional high-risk (FHR) multiple myeloma (FHRMM) is often defined as progression within 12-24 months of front-line autologous hematopoietic stem cell transplantation (AHSCT). For patients with early progression after suboptimal front-line therapies, it is challenging to assign the disease progression to a true FHR phenotype versus less effective front-line therapy. In this study, we combined data from three Center for International Blood and Marrow Transplant Research studies (MM18-02, MM19-01 and MM20-03). We included patients who received front-line AHSCT between 2008 and 2018 and had progression <12 (FHR12, n = 465), <18 (FHR18, n = 672) or <24 months (FHR24, n = 853) after AHSCT. We classified induction therapy as standard lenalidomide-containing triplets (bortezomib, lenalidomide, dexamethasone VRD/carfilzomib, lenalidomide, dexamethasone KRD) versus other (bortezomib, thalidomide, dexamethasone VTD/bortezomib, cyclophosphamide, dexamethasone VCD/bortezomib, dexamethasone VD/lenalidomide, dexamethasone RD) and studied the impact of front-line therapy on post-FHR overall survival (OS). In the FHR12 cohort (follow-up 48 months), the OS after VRD/KRD (n = 238) was 21 versus 17 months with other regimens (n = 227, hazard ratio HR = 1.2, 95% confidence interval CI: 0.6-1.06). In a multivariable model, the HR for OS was 0.94 (95% CI: 0.7-1.3, p = 0.69) for VRD/KRD versus other regimens. There was no significant interaction between type of first-line (1L) therapy and time from 1L AHSCT to first relapse in predicting OS. Similar results were seen for FHR18 and FHR24. FHRMM remains a negative prognostic factor irrespective of front-line therapy and warrants consideration of T-cell engagers' second-line therapy.
Goel et al. (Thu,) studied this question.