Predictors of Lenalidomide Refractory Relapse Timing With Newly Diagnosed Multiple Myeloma: A FIRST Trial Subanalysis

Treatment-refractory relapse timing, CRAB symptoms, and baseline characteristics may predict outcomes in patients with newly diagnosed multiple myeloma. Late relapse ( >= 12 months; n = 186) was associated with better survival versus early relapse ( < 12 months; n = 203). Lower lactate dehydrogenase, /32 microglobulin, and IgG subtype predicted late relapse. Considering these factors can help identify treatments for patients with early relapse risk.Introduction/Background: Multiple myeloma (MM) is considered an incurable cancer. Patients with newly diagnosed MM (NDMM) are at risk for relapse within 1 year of frontline therapy. The immunomodulatory agent lenalidomide combined with dexamethasone (Rd) may be used as treatment for NDMM or relapsed MM, including in patients ineligible for autologous stem cell transplant.Patients: This subanalysis of the phase III FIRST trial characterized patients with transplant-ineligible NDMM who experienced relapse while receiving Rd therapy by relapse timing (early [<12 months] versus late [>= 12 months]) and type (CRAB vs. non-CRAB).Methods: The Kaplan-Meier product limit method was used to estimate time-to-event endpoints, including progression-free survival (PFS) and overall survival (OS). Factors associated with the odds of late relapse were identified by logistic regression with univariate and multivariate analyses using a binary outcome (relapse at <12 vs. >= 12 months) in patient-, disease-, and treatment-specific baseline variables.Results: Patients with early refractory relapse had functionally high-risk disease and inferior outcomes. In patients with early relapse versus those with late relapse, median OS (95% CI) was 26.8 months (21.9-32.8) versus 63.9 months (57.0-78.0), median OS from disease progression to death was 19.9 months (16.0-25.5) versus 36.4 months (27.9-47.0), and median PFS from randomization to second progression was 19.1 months (17.3-22.5) versus 42.1 months (37.4-44.9). Lactate dehydrogenase, baseline beta 2 microglobulin, and myeloma subtype were shown to predict time to relapse.Conclusions: Clinicians could use these factors to consider more aggressive treatment regimens for those at highest risk of early relapse.