Quadruplet Regimens for NDMM
Frontline therapy
Frontline therapy is the first treatment given to patients with newly diagnosed multiple myeloma (NDMM). Frontline therapy has a long-term effect on patients with myeloma as their first remission is usually their longest. This is why the choice of frontline therapy is so important for patients. Myeloma doctors strive for higher response rates with lower rates of side effects. Response to treatment refers to a clinically meaningful improvement in the signs and symptoms of myeloma.
Biology of myeloma
The biology of myeloma is complex. Extensive research has established that myeloma is controlled better with multiple drugs from different drug classes than with a single drug. Different mechanisms of action (MoA), the process through which a drug induces its effect in the body, have different ways of attacking myeloma. Each drug can enhance the activity of the other drugs in a combination therapy.
Triplet regimens
For many years, the standard of care for patients with NDMM was the “triplet” (3-drug) combination of the proteasome inhibitor Velcade® (bortezomib) + the immunomodulatory agent Revlimid® (lenalidomide) + the steroid dexamethasone [VRd]. The other commonly used triplet, primarily for transplant-ineligible patients, has been the monoclonal antibody Darzalex® (daratumumab) + Revlimid + dexamethasone [DRd]. (continues on reverse side)
Quadruplet regimens
As of August 2025, the U.S. Food and Drug Administration (FDA) has approved two “quadruplet” (4-drug) VRd-based combination therapies for NDMM, which demonstrated impressive improvements in progression-free survival (PFS) and overall survival (OS) when compared to VRd alone:
DVRd
In July 2024, the FDA approved the combination of monoclonal antibody Darzalex Faspro® (daratumumab hyaluronidase-fihj) + VRd [DVRd] for induction therapy (initial treatment given in preparation for a transplant) and consolidation therapy (treatment given to deepen response after transplant) in patients with NDMM who are eligible for autologous stem cell transplant (ASCT).
Isa-VRd
In September 2024, the FDA approved the combination of monoclonal antibody Sarclisa® (isatuximab-irfc) + VRd [Isa-VRd] for patients with NDMM who are not eligible for ASCT.
Based on data emerging from currently ongoing clinical trials, FDA approvals of other quadruplet regimens are anticipated in the near future.
Sign up at subscribe.myeloma.org for the IMF’s weekly e-newsletter Myeloma Minute, as well as alerts about IMF news, events, and actions.
Use the QR code or visit medications.myeloma.org for more information.
As always, the IMF urges you to discuss all medical issues with your doctor and to contact the IMF InfoLine with your myeloma-related questions and concerns at 1.818.487.7455 or InfoLine@myeloma.org .
myeloma.org