Dr Richardson on the Role of Quadruplet Regimens in Newly Diagnosed Myeloma

“What's interesting is that in terms of the patient populations, transplant is not used in either of these trials, but the patient population for [isatuximab plus] VRd may be a little more enriched for frailty, but that being said, the CEPHEUS data are very similar to [that of] isatuximab [plus VRd].”

Paul G. Richardson, MD, the RJ Corman Professor of Medicine at Harvard Medical School and clinical program leader and director of Clinical Research of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, discussed the role of quadruplet regimens for the treatment of patients with newly diagnosed multiple myeloma.

The combination of daratumumab (Darzalex) and bortezomib (Velcade), lenalidomide (Revlimid)m and dexamethasone (VRd) has demonstrated success when combined with autologous hematopoietic stem cell transplantation (ASCT) in the phase 2 GRIFFIN trial (NCT02874742) and phase 3 PERSEUS trial (NCT03710603), Richardson began. He also noted that daratumumab plus VRd was explored in the phase 3 CEPHEUS trial (NCT03652064) in patients who were ineligible for or deferred ASCT. Notably, data from the phase 3 IMROZ trial (NCT03319667) revealed similar outcomes when patients ineligible for ASCT received isatuximab-irfc (Sarclisa) plus VRd, he emphasized. However, he added that the patient population treated with isatuximab plus VRd may be more enriched for frailty. The similarities lie in the duration of disease control with daratumumab plus VRd and isatuximab plus VRd, which surpassed expectations, he said.

In addition to the efficacy of these quadruplet regimens, Richardson noted that the delivery of these treatments has improved over time. For example, the administration of daratumumab has turned to subcutaneous injection, which has opened the door for significant change, as patients are no longer required to stay at infusion centers for hours, he explained. With isatuximab, the shorter infusion times also contribute to convenience, because it’s less complement activating, and therefore infusion reactions are not a large concern. Notably, he described that isatuximab will be coming into the subcutaneous space and looks promising.

Although isatuximab and daratumumab do not have the same complement activation, this may make complement activation more challenging when using daratumumab, as the agent could be preferred among patients with chronic obstructive pulmonary disease or more reactive airways, Richardson concluded.