Efficacy in Clinical Trials vs Effectiveness in the Real World for Multiple Myeloma Treatment Regimens

Kelvin Chan, MD, PhD, the Ottawa Hospital Research Institute, Ontario, Canada, and colleagues recently investigated the efficacy of registrational randomized controlled trials (RCTs) vs the real-world (RW) effectiveness for patients using standard of care regimens for multiple myeloma (MM). The study consisted of three primary outcomes: progression-free survival (PFS), overall survival (OS), and serious adverse events (AEs).

The authors pulled data from the Institute for Clinical Evaluative Sciences in Ontario, Canada, on patients with multiple myeloma who had been treated with a standard of care regimen between January 2007 and December 2020. The study consisted of 3951 real-world patients with MM who were treated with the following seven regimens: lenalidomide + dexamethasone (Rd) and bortezomib + dexamethasone (VRd) for newly diagnosed, transplant-ineligible patients, and carfilzomib + lenalidomide + dexamethasone (KRd), carfilzomib + dexamethasone (Kd), daratumumab + lenalidomide + dexamethasone (DRd), daratumumab + bortezomib + dexamethasone (DVd), and pomalidomide +  dexamethasone (Pd) for patients with relapsed refractory MM (RRMM).

To determine the gap in PFS and OS outcomes between RW and RCT patients, Dr Chan and colleagues performed meta-analyses. For the RW cohort, PFS was defined as the time from the start of the treatment regimen until death, initiation of subsequent MM treatment, or last follow-up. The authors used hospital admissions data during treatment with the index regimen as a surrogate for serious AEs in the RW cohort, which was abstracted from published RCTs.

The study found that for six out of the seven regimens, the patients with MM who had been treated in the real world had a worse PFS compared to the “highly selected” patients in the RCTs, with a hazard ratio (HR) of 1.44 (95% CI, 1.34-1.54). In addition, they had worse OS outcomes compared to the RCT patients (HR of 1.75 [95% CI, 1.63-1.88]).

Notably, real-world patients with RRMM had previously been exposed to lenalidomide at higher rates vs the RCT patients. The authors note, “. . . perhaps patients included in the MM-003 RCT may have had more RRMM (given the higher prior immunomodulatory drug exposure and longer time from diagnosis to treatment among Pd RCT patients) compared to RW patients in this study.” As such, the Pd regimen was the only regimen that resulted in better outcomes in the real-world cohort compared to the RCT cohort.

Both cohorts experienced similar rates of inpatient hospitalization and AEs while receiving their treatment regimens (VRd 57% vs not reported [NR]; Rd 64% vs NR; Kd 57% vs 59%; KRd 53% vs 60%; DVd 36% vs NR; DRd 46% vs 49%; Pd 59% vs 61%).

The aim of this study was to further investigate the efficacy-effectiveness gap between registrational RCTs and real-world use of MM treatment regimens. Overall, the research found that the real-world patients with MM had 75% worse OS vs RCT patients. In addition, they experienced 44% worse PFS than the RCT cohort. The results highlight the need for ongoing examination of real-world data for patients with MM in order to better “contextualize effectiveness and toxicity of selected regimens in the clinic.”

Reference: Chan KKW, Seow H, Pond G, et al. Comparison of the Efficacy in Clinical Trials Versus Effectiveness in the Real-World of Treatments for Multiple Myeloma: A Population-Based Cohort Study. Presented at: 2023 ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA, and virtual; Abstract 541.