Dr Dorritie on the Role of Quadruplet Regimens in Multiple Myeloma

“Any patient [with multiple myeloma] who can possibly tolerate a quadruplet [regimen] should be offered a quadruplet because we [can] improve overall response rates and rates of [minimal residual disease] negativity [with these regimens], which translate into progression-free survival benefits.”

Kathleen A. Dorritie, MD, a hematologist/medical oncologist at the University of Pittsburgh Medical Center Hillman Cancer Center, discussed the role of quadruplet regimens for the treatment of patients with multiple myeloma.

Although triplet regimens have remained the standard of care for patients with multiple myeloma for a significant amount of time, quadruplet regimens are becoming more relevant for these patients, Dorritie began. A significant amount of data have emerged, particularly in the transplant-eligible setting, from the phase 2 GRIFFIN trial (NCT02874742) and the phase 3 PERSEUS trial (NCT03710603), she noted. The studies compared quadruplet regimens with triplet regimens, she explained.

For example, in GRIFFIN, daratumumab (Darzalex) plus lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (D-RVd) was compared with lenalidomide, bortezomib, and dexamethasone (RVd) in patients with newly diagnosed multiple myeloma. At a median follow-up of 49.6 months (IQR, 47.4-52.1), the stringent complete response rate was 67% in the D-RVd arm (n = 100) compared with 48% in the RVd arm (n = 98; odds ratio, 2.18; 95% CI, 1.22-3.89; P = .0079). Of note, the 4-year progression-free survival (PFS) rate was 87.2% (95% CI, 77.9%-92.8%) in the investigational arm compared with 70.0% (95% CI, 55.9%-80.3%) in the control arm.

Furthermore, patients who are considered transplant-ineligible or transplant deferred were included in the phase 3 IMROZ (NCT03319667), CEPHEUS (NCT03652064), and BENEFIT (NCT04751877) trials, Dorritie continued. Data from these trials demonstrated that patients who can potentially tolerate a quadruplet regimen should be offered a quadruplet regimen instead of a triplet due to improved overall response rates, along with minimal residual disease negativity, which can lead to PFS benefits, she said.

Overall, the takeaway is that quadruplet regimens should be given to all patients with multiple myeloma if eligible, and triplet regimens to those who are ineligible for quadruplet. These regimens are more widely used in clinical practice, as doublet regimens are no longer a standard of care option, Dorritie concluded.