Quadruplet Regimen Preferable to Triplets in Multiple Myeloma

When weighing treatment options for patients with multiple myeloma, a four-drug treatment regimen is currently preferable to treatment with three drugs, as Dr. Cesar Rodriguez explained.

“What we need to keep in mind is that our first shot is always going to be our best shot at controlling myeloma, and it's going to give us the longest duration of response,” said Rodriguez during the CURE Educated Patient® Multiple Myeloma Summit. “So, we want to use the most effective drugs, up front. Now, as we add monoclonal antibodies, bispecific T cell engagers and CAR-T [cell therapy], we might not have to add all four classes of drugs. We might be able to do away with some of them, but for now, four drugs is still better than three, until we learn if CAR-T or bi-specific T cell engagers can come to the front line. And adding a monoclonal antibody does not add toxicity to the standard three-drug regimen.”

Rodriguez is an associate professor of medicine (hematology and medical oncology) at the Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute and the Center of Excellence for Multiple Myeloma, and serves as Clinical Director of Multiple Myeloma at The Mount Sinai Hospital in New York City. He gave a talk on “Triplets or Quadruplets: Navigating Treatment Options” during the summit.

During the summit, Rodriguez discussed the phase 3 CEPHEUS trial evaluating the addition of the monoclonal antibody Darzalex (daratumumab) to Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone (VRd) in patients with transplant-ineligible or -deferred newly diagnosed multiple myeloma, findings from which were presented at the 2024 ASH Annual Meeting. The combination, known as D-VRd demonstrated improved minimal-residual disease responses and complete response rate, and led to improved progression-free survival, regardless of MRD negative or positive status.

“We see here that by adding this fourth agent to three agents, there really is an added benefit in terms of the depth of the response and the control of the disease,” Rodriguez said. “And one would say, ‘OK, well, why are we doing this in somebody who's frail or who's transplant ineligible?’ It's a very good question, and we need to figure out, ‘OK, what is our goal for the treatment?’ Is our goal the treatment to achieve a remission and a durable remission, or is the goal of our treatment to just maintain the disease and to keep it from growth? If we really want to try to knock off the disease from the patient and we want to try to get the best control possible, then a combination of four drugs is possible, as you can see by this study.”

Rodriguez also discussed a number of phase 3 clinical trials that challenged the role of triplet regimens as induction or consolidation therapy in transplant-eligible patients, including the EMN17/PERSEUS, GMMG-HD7 and EMN24/ISKIA trials.

The PERSEUS trial, for example, showed that D-VRd followed by autologous stem cell transplant (ASCT), followed by D-VRd consolidation and Darzalex plus Revlimid (DR) maintenance improved rates of sustained minimal residual disease negativity compared with VRd induction, ASCT, VRd consolidation and Revlimid maintenance in transplant-eligible patients with newly diagnosed multiple myeloma, according to updated data presented at the 2024 SOHO Annual Meeting.

“When we add the monoclonal antibody and we see how it's controlling the disease up front, and it's maintaining the disease very well controlled, even after 12 months, compared to just doing three drugs,” said Rodriguez. “And in terms of safety, there was a slight increase in infections, but this was very minimal and not statistically significant to say, ‘OK, the amount of infections we're getting definitely are worse than the responses and the benefit that we're getting from the drug.’ So thanks to that, the D-VRd got approved [by the FDA] for use here in the United States.”

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