Whether newly diagnosed or living with multiple myeloma for years, patients and their loved ones are witnessing remarkable advancements in treatment. Here, we highlight some of the most recent breakthroughs.
In 2024, the FDA approved two four-drug combinations for newly diagnosed multiple myeloma (NDMM). DVRd, comprising Darzalex Faspro® (daratumumab plus hyaluronidase-fihj), Velcade® (bortezomib), Revlimid® (lenalidomide), and dexamethasone, is approved for transplant-eligible patients. IsaVRd, including Sarclisa® (isatuximab), Velcade, Revlimid, and dexamethasone, is approved for those not eligible for transplant.
Why are these approvals significant? The drugs used in frontline therapy greatly impact long-term outcomes, namely the depth of response and the duration of that response. This is particularly important as the first remission is typically the longest. Quadruplet combinations combat the complex biology of myeloma, achieving response rates over 90% by combining drugs with different mechanisms of action. Although patients do experience side effects, they are mostly manageable with these newer treatments. This means patients can enjoy longer and better-quality lives.
Advancements in relapse therapies
Despite these great advances, myeloma does relapse in nearly all patients. Great progress is being made by exploring the potential of moving CAR T-cell therapies and bispecific antibodies — typically used after late relapse — into earlier-line treatment. Indeed, in 2024, the FDA approved both CAR T-cell therapies — Carvykti® (ciltacabtagene autoleucel) and Abecma® (idecabtagene vicleucel) in earlier relapse (as soon as first relapse). Clinical trials are investigating bispecific antibodies, like Tecvayli™ (teclistamab), early relapse, and even frontline therapy. These developments could further transform initial myeloma care.
The “Down with Dex” movement
For many, the steroid dexamethasone may be a dreaded myeloma treatment due to its significant side effects, including insomnia, psychiatric issues, and diabetic complications. Fortunately, recent research shows that reducing dexamethasone doses in newly diagnosed patients does not compromise progression-free survival (PFS) or overall survival (OS).
Historically, high doses of dexamethasone were standard, but studies like the ECOG E4A03 trial have demonstrated better outcomes and fewer side effects with reduced dosing. Recent analysis of the SO777 and S1211 trials confirms that dose reductions are both effective and tolerable. This research shows the need to tailor dexamethasone dosing to individual patient characteristics, potentially minimizing side effects, improving quality of life, and supporting long-term treatment adherence.
Treating high-risk smoldering multiple myeloma
Multiple myeloma develops from precursor conditions, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which is categorized into low-, intermediate-, and high-risk groups. In December 2024, a notable study presented at the 66th American Society of Hematology (ASH) Meeting & Exposition focused on high-risk SMM. It compared observation with treatment using single-agent daratumumab, finding significant benefits with treatment in both time to progression to active myeloma as well as overall survival. This will likely change our practice very soon.
Approaches to disease monitoring
Minimal residual disease (MRD) refers to the small number of myeloma cells that may remain after treatment, often undetectable by standard tests. MRD testing, however, can identify one myeloma cell among a million healthy cells, making it an invaluable tool for monitoring disease.
In research settings, MRD testing has guided treatment decisions, allowing some patients to pause therapy once MRD-negative status is achieved. It is very clear that MRD testing will guide more of our therapies and will allow some patients to reduce if not even discontinue treatment.
Staying informed and taking action
These highlights represent just a fraction of the ongoing advances in myeloma research. To stay updated, consider subscribing to the International Myeloma Foundation’s e-newsletter, “The Myeloma Minute,” or visiting myeloma.org.
March is Myeloma Action Month, an opportunity to raise awareness and share resources. Join the movement by sharing graphics and stories from mam.myeloma.org.
Together, we can ensure patients and their loved ones have the information and support they need to navigate the ever-improving landscape of multiple myeloma.
