SAN DIEGO — Two frontline therapy combinations for patients with multiple myeloma who are not eligible for hematopoietic stem cell transplant are listed as "preferred" regimens, according to National Comprehensive Cancer Network guidelines.
However, a new analysis of real-world patient outcomes suggests that one regimen may be significantly better.
The study found that frontline triple therapy with daratumumab plus lenalidomide and dexamethasone led to significantly longer time to next treatment or time to death compared with the triple combination that includes bortezomib instead of daratumumab.
In the absence of head-to-head randomized controlled clinical trials, this study may help clinicians make more informed decisions when choosing therapies for patients with newly diagnosed, transplant-ineligible multiple myeloma, said investigator Doris K. Hansen, MD, from the Moffitt Cancer Center & Research Institute in Tampa, Florida, who presented finding from the analysis at the American Society of Hematology (ASH) annual meeting.
Despite the lack of head-to-head randomized trials in this setting, several indirect comparisons have suggested that the daratumumab regimen carries an efficacy edge.
For instance, an indirect comparison of patients who received the daratumumab regimen in the MAIA trial with those who received the bortezomib regimen in the SWOG S0777 trial revealed a 40% lower risk for disease progression or death among patients treated with daratumumab. Researchers also observed a benefit for the daratumumab regimen — a 32% lower risk for disease progression or death — when comparing patient outcomes in the MAIA and PEGASUS studies.
To more directly compare the efficacy of the two regimens, Hansen and colleagues combed data from Acentrus, a de-identified academic electronic medical records database, to find patients who started a frontline treatment regimen for multiple myeloma between January 2018 and May 2023. The team used several methods to balance baseline characteristics between cohorts.
After making these adjustments, the study included data on 302 patients who received frontline therapy with the daratumumab regimen and 341 who received the bortezomib regimen. Patients who underwent hematopoietic stem cell transplant before or during therapy were excluded, as were those who had prior primary solid tumors, hematologic malignancies, or amyloidosis.
During a 20.2-month median follow-up for patients on daratumumab, 98 (32%) switched to a new therapy or died. During a 21.5-month median follow-up for those on bortezomib, 175 (51%) switched treatments or died.
The median time to death was 37.8 months in the daratumumab group vs 18.7 months in the bortezomib group. Overall, patients who received the daratumumab regimen had a 42% lower risk for death or time-to-next treatment (adjusted hazard ratio [HR], 0.58; P < .001).
Hansen acknowledged several limitations of the study, including that the data used came from provider-based records and may be missing patients who saw an out-of-network clinician. The database also does not include information on ECOG performance status, patient frailty, or cytogenetic risk profiles, which may have influenced outcomes.
The outcome measure combined time-to-next treatment and time to death; however, Hansen noted, time-to-next treatment is not a direct surrogate for progression-free survival.
Overall, findings from this real-world study support the use of daratumumab plus lenalidomide and dexamethasone over bortezomib plus lenalidomide and dexamethasone in this population of transplant-ineligible patients with newly diagnosed multiple myeloma, Hansen concluded.
The study was supported by Janssen. Hansen reported consulting for Janssen and others, receiving honoraria from OncLive and Survivorship, and other disclosures.
Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.
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