Paul G. Richardson, MD, Considers How Data Surrounding Standard Triplet Therapies in Myeloma Inform Use of Newer Regimens

Paul G. Richardson, MD, presented data from the phase 3 DETERMINATION study at 2022 ASCO and theorized how these findings could extend to similar regimens in newly diagnosed multiple myeloma.

At the 2022 American Society of Clinical Oncology Annual Meeting, Paul G. Richardson, MD, clinical program leader and director of clinical research for the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute as well as RJ Corman Professor of Medicine at Harvard Medical School, both in Boston, Massachusetts, presented data from the phase 3 DETERMINATION trial (NCT01208662) that examined the efficacy of lenalidomide (Revlimid), bortezomib, and dexamethasone (RVd) followed by continuous lenalidomide maintenance and delayed autologous stem cell transplant (ASCT) vs immediate ASCT. Given the recent shift in the field to rely more heavily on quadruplet therapies, he considers how these data can be used to inform the current paradigm.


The implications for clinical practice are big. The important thing to remember is this is a triplet [regimen], and the field has already moved into quadruplets. We’re [regularly] using the 3-drug platform of a proteasome inhibitor, an IMiD [immunomodulatory drug], and a steroid, but with an antibody added. That’s already moved the goalposts yet further in the right direction. We know, for example, that if you combine RVd or KRd [carfilzomib (Kyprolis), lenalidomide, and dexamethasone] with daratumumab [Darzalex], the results are dramatic with or without transplant. This is becoming a very exciting new area.

This study provides a foundation for interpreting and understanding these new results. At the same time, given the adoption of quadruplet therapy in the community because of the excellent data from various studies supporting it, we’re seeing even more innovative approaches. How can you bring CAR T-cell therapy, bispecific antibodies, and next-generation small molecules into the early treatment of patients to improve outcomes? I also believe that clearly the effect of melphalan matters. The question is, how can we do better? We also have exciting new drugs in the pipeline.


Richardson PG, Jacobus SJ, Weller E, et al. Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed multiple myeloma (NDMM): The phase 3 DETERMINATION trial. J Clin Oncol. 2022;40(suppl 17):LBA4. doi:10.1200/JCO.2022.40.17_suppl.LBA4