Multiple Myeloma Treatment Advancements

There are many types of drugs that treat multiple myeloma (MM), like monoclonal antibodies, immunomodulators, and proteasome inhibitors. They target and destroy cancer cells. The outlook for longer survival with MM continues to improve with the approval of new classes of medications and new combinations of existing medications that are both more effective and less debilitating.

These lab-made proteins were first introduced for the treatment of relapsed multiple myeloma in 2015 and are given intravenously. They mimic the antibodies made by your own immune system. They bind to certain proteins on myeloma cells and kill them. Daratumumab (Darzalex), developed in 2015, was a game changer. In 2026, it was added to the triple therapy of bortezomib, lenalidomide, and dexamethasone as a first-line treatment. Isatuximab (Sarclisa) is another possible addition to that triple therapy. Elotuzumab (Empliciti) is a monoclonal antibody for relapsing MM. It is used in combination with certain other treatments.

Bispecific antibodies are drugs made up of two antigen-binding sites. One activates your T cells, while the other targets a protein on myeloma cells. These drugs are for people whose multiple myeloma didn’t respond or respond well enough to other regimens. Examples include elranatamab (Elrexfio) and teclistamab (Tecvayli), both of which go after the BCMA protein on myeloma cells, and talquetamab-tgvs (Talvey), which attacks the protein GPRC5D and is an option when certain other drugs don't work. Most bispecific antibodies are given as a shot and some are given through an IV.

These drugs have the potential to be a major step forward in therapy for multiple myeloma, especially resistant or relapsing MM. Currently, there’s no standard dosing schedule, and clinical trials are in progress. Trispecific antibodies target both BCMA and GPRC5D, plus they activate the protein CD3 on your T cells. At least three combinations of trispecific antibodies are in early clinical trials. Results for people with returning or hard-to-treat MM are promising, and the FDA has fast-tracked at least two trials, those for ISB 2001 and IBI3003, opening them up to more participants. Approval could be years sooner than normal, with advance access possible.

These are combination drugs that pair a monoclonal antibody with a chemotherapy drug. The antibody recognizes the BCMA protein on the cancer cells and the chemo agent kills them. One antibody-drug conjugate approved in October 2025 is belantamab mafodotin-blmf (Blenrep). This therapy is for people with relapsed or refractory (hard to treat) multiple myeloma, or RRMM, who have received at least two prior types of treatment.

These are a specialized, targeted form of MM therapy designed to focus radiation in tumor tissue. The concept is the same as antibody-drug conjugates (ADCs), but instead of pairing a monoclonal antibody with a chemo drug, it uses isotopes that bond to and kill cancer cells. There are nine radio-conjugates in the preclinical stage or in early-stage clinical trials. Most far along in the study process is the radiotherapeutic iopofosine I-131, now in a phase 2B trial. Radioconjugates are designed for people with RRMM.

Cereblon E3 ligase modulatory drugs or CELMoDs are a new type of multiple myeloma medication, one that comes in pill form. Beyond killing myeloma cells directly, these meds also engage other immune cells. 

Iberdomide (Zenbexus) was recently FDA-approved in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd) for treatment of multiple myeloma in adults who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. Another CELMoD, mezigdomide, is in clinical trials. Early findings show that mezigdomide may be better for those who relapsed early or whose prior treatments were unsuccessful.

Another new and novel type of drug, EP300/CBP bromodomain inhibitors are designed to block the activity of EP300 and CBP proteins. When overactive, those proteins promote tumor growth. By stopping them, two of the gene mutations that drive cells in myeloma, IRF4 and MYC, can be stemmed. The EP300/CBP bromodomain inhibitor inobrodib in combination with pomalidomide and dexamethasone is being studied in a phase 1/2a trial of people with RRMM. OPN-6602 is another bromodomain inhibitor in a phase 1 clinical trial with results expected by the end of 2026. The FDA granted it the orphan drug designation in February 2025, which could shorten the typical length of the drug approval process.

CAR T-cell therapy is a type of immunotherapy introduced for treatment of multiple myeloma in 2021. It involves removing and making changes to your own T cells to attack BCMA proteins on cancerous cells. You’ll get your reengineered cells back via a transfusion, but the process can take up to two months. Aimed at people with RRMM, available drugs include idecabtagene vicleucel (Abecma) and cilta-cel or ciltacabtagene autoleucel (Carvykti). Other CAR T-cell drugs being studied target the protein GPRC5D or both BCMA and GPRC5D. These include RD118, which uses fully human CAR T cells that attack GPRC58 proteins on cancerous cells.

Scientists at Dana-Farber Cancer Institute are developing a therapy called CAR-Enhancer, or CAR-E. It has the potential to boost the effectiveness and longevity of traditional CAR T-cell treatment by prompting CAR T cells to form a memory of the cancer cells. Then they can spring back into action if MM returns.

Dana-Farber is also running a study comparing CAR T-cell therapy with cilta-cel to autologous stem cell transplant after induction therapy with daratumumab, lenalidomide, bortezomib and dexamethasone in newly diagnosed people with MM to see what’s more effective.

New drug combinations are being studied, with one already available.

• The FDA recently approved the immunotherapy pairing of the bispecific antibody teclistamab and the anti-CD38 monoclonal antibody daratumumab plus hyaluronidase-fihj (Darzalex Faspro) for people who had at least one prior form of therapy. It had an 89% response rate in its phase 3 study called MajesTEC-3.
• The combination of the bispecific antibody talquetamab plus daratumumab have shown effective results. Tec-DP, or teclistamab, daratumumab and pomalidomide (an oral immunomodulator), are being studied as an option for RRMM.
• A Phase 1/2 trial is looking at the combination of the drug selinexor, which blocks the XPO1 protein, and the CELMod mezigdomide for people with RRMM who weren't helped by or can't have CAR T-cell treatment.