Does Treatment Sequencing Impact Survival in Transplant-Ineligible MM?

A simulation “supports the use” of daratumumab, lenalidomide, and dexamethasone as an initial therapy in patients with transplant-ineligible newly diagnosed multiple myeloma (MM), according to a recent study.

Rafael Fonseca, MD, of the Mayo Clinic and colleagues performed the clinical simulation to “assess potential outcomes with different treatment sequences.”

They used a partitioned survival model to compare overall survival (OS) among three treatment strategies:

• First-line daratumumab, lenalidomide, and dexamethasone followed by a second-line pomalidomide- or carfilzomib-based regimen
• First-line bortezomib, lenalidomide, and dexamethasone followed by a second-line daratumumab-based regimen
• First-line lenalidomide and dexamethasone followed by a second-line daratumumab-based regimen

They used published clinical and real-world data from the Flatiron health database to determine the probabilities of transitions among health states, which were first-line therapy, second-line or later therapy, and death. Dr. Fonseca and colleagues estimated the proportion of patients discontinuing treatment after first-line therapy with a binomial logistic model using data from the MAIA trial.

The simulation showed that using first-line daratumumab, lenalidomide, and dexamethasone conferred a median OS of 8.9 years. It showed that using daratumumab-based regimens as second-line therapies following bortezomib, lenalidomide, and dexamethasone conferred a median OS of 6.92 years, while using daratumumab-based regimens after lenalidomide and dexamethasone conferred a median OS of 5.75 years.

“Results of scenario analyses were consistent with the base case,” Dr. Fonseca and colleagues wrote. “Our simulation, which incorporates clinically representative treatments and attrition rates, supports the use of [daratumumab, lenalidomide, and dexamethasone] as initial therapy, rather than delaying the use of daratumumab until later lines of therapy, in patients with transplant-ineligible [newly diagnosed] MM.”

Reference

Fonseca R, Facon T, Hashim M, et al. Impact of treatment sequencing on overall survival in patients with transplant-ineligible newly diagnosed myeloma. Oncologist. 2023;28(5):e263-e269. doi:10.1093/oncolo/oyad053