Luciano Costa, MD, PhD, Discusses the Rationale for Examining Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma

At the 2021 International Myeloma Workshop, CancerNetwork® spoke with Luciano Costa, MD, PhD, of O’Neal Comprehensive Cancer Center, about the rationale for the phase 2 MASTER trial (NCT03224507), which examined daratumumab (Darzalex), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone in patients with newly diagnosed multiple myeloma. Additionally, investigators examined how minimal residual disease may be used to tailor treatment with this regimen. 

Transcript:

The [MASTER] study came about due to the recognition that patients with multiple myeloma can have a very heterogeneous disease that responds very differently to therapy, and some patients have outstanding response that can last many years. Some patients have a very short duration of response, regardless of what you do. Also, patients tend to achieve different levels of response at different time points. However, the treatments have been developed in clinical trials where every patient in a certain arm gets the same treatment.

The attempt here was to take a very powerful 4 drug combination leveraging the best and most established classes of therapy in myeloma [that were] combined safely to achieve a deep response [and] utilizing transplant given its known benefit in deepening responses in most patients. [From there, therapy can be] tailored to the achievement of [minimal residual disease] (MRD) negativity, not only at a single point, but also confirming at least 2 consecutive points. As a consequence, some patients need very brief therapy, and some patients need longer therapy. We also explored the possibility of [withholding maintenance therapy in] those patients who have confirmed MRD-negative responses, coming from the perspective that the role of maintenance therapy although well-established, was well established at a time when regimens did not lead to frequent, deep responses. Those patients could do very well with omission of therapy, alleviating the financial and physical burden of continuous therapy and, in exchange, monitoring disease using this very sensitive techniques that we have with MRD.

Reference

Costa LJ, Chhabra S, Medvedova E, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd), autologous transplantation and MRD response-adapted treatment duration and cessation in newly diagnosed multiple myeloma (NDMM). Paper presented at: 18th International Myeloma Workshop; September 8-11, 2021; Vienna, Austria. Accessed September 11, 2021.