Unpacking Data From Pivotal Trials in Multiple Myeloma: Shining a Light on the MASTER Trial Evaluating D-KRd

In this second episode of OncChats: Unpacking Data From Pivotal Trials in Multiple Myeloma, Hamza Hashmi, MD, of the Medical University of South Carolina, discusses the depth of response reported with daratumumab, carfilzomib, lenalidomide, and dexamethasone in transplant-eligible multiple myeloma.

The second clinical trial that I would like to discuss was presented at the [2022] ASCO [Annual] Meeting was the MASTER study [NCT03224507]. Here, investigators looked at a very potent quadruplet induction regimen of daratumumab [Darzalex], carfilzomib [Kyprolis], lenalidomide [Revlimid], and dexamethasone [D-KRd] for patients with transplant-eligible, newly diagnosed multiple myeloma.

In this phase 2, single-arm trial, patients received 4 cycles of induction [treatment] with D-KRd followed by high-dose melphalan and stem cell rescue, followed by 4 to 8 cycles of consolidation [treatment] with D-KRd.

Minimal residual disease [MRD] assessments were done before transplant, after 4 and 8 cycles of consolidation, and any time patients achieved sustained MRD negativity, which was defined as [having] MRD (determined by clonoSEQ) at 10-5 and sustained for least 4 to 8 full cycles. Patients entered into an MRD surveillance phase, where they just underwent observation without any consolidation or maintenance [treatment]. 

The trial showed us that D-KRd was associated with very deep responses, with MRD negativity 105 seen in about 80% of the patients and MRD negativity 106 seen in about 66% of the patients. Sustained MRD negativity 105 sustained at least 4 cycles or 4 months apart, was seen in about 70% of the patients. Seventy percent of the patients entered the MRD surveillance phase and had follow-up [data] presented after 2 years. [Here,] we learned that patients who had standard-risk multiple myeloma and zero or only one high-risk cytogenetic abnormality did not have any significant progression despite not being on maintenance [treatment]. Having said that, patients who had two or more high-risk cytogenetic abnormalities experienced progression very early after entering this observation or surveillance phase [of the research]. We learned from this clinical trial that D-KRd is a very strong, potent induction regimen—especially for [patients with] high-risk multiple myeloma, so those who have lesion 17p, translocation 4:14, translocation 14:16, and gain or amplification 1q. It leads to deep remissions in these patients.

Whether we can stop all chemotherapy after achieving sustained MRD negativity for 4 months or 4 cycles apart for a [patient with] standard[-risk] multiple myeloma needs to be determined with longer follow-up. The trial very clearly showed us that for patients who have high-risk [disease], with 2 or more high-risk cytogenetic abnormalities, taking them off chemotherapy—whether consolidation or maintenance—is perhaps not the right strategy, as these patients relapse very quickly after stopping chemotherapy.

Check back next Wednesday for the next episode in this series.