Multiple Myeloma Treatment Advances: Five Things to Know 

For patients with multiple myeloma, an incurable cancer that affects blood plasma cells, there are many new options for treatment that are producing better, and increasingly long-lasting outcomes. Approved options include immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies. More recently, immunotherapies such as CAR T-cell therapies and bispecific antibodies for patients with relapsed disease not responding to current treatment are showing great promise.  

There also are therapies under investigation that show similar promise for patients with relapsed/refractory multiple myeloma, newly diagnosed multiple myeloma, and a pre-cancerous condition called smoldering myeloma, with a beneficial impact felt across the whole spectrum of disease. 

“This is a very  encouraging time for our patients,” says Paul G. Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber. “We have many novel agents to work with, but we still have much more work to do because myeloma remains a difficult-to-treat disease. There is an increasing population of patients benefitting from novel therapies and enjoying prolonged disease control, but in subset of about a third overall who have high-risk disease, durable control and prolonged remissions can be very hard to achieve.” 

Multiple immunotherapy options for relapsed/refractory myeloma 

Immunotherapy refers to treatments that use the body’s own immune system to combat diseases such as cancer. 

CAR T-Cell Therapy: Currently, there are two CAR T-cell therapies approved for relapsed/refractory multiple myeloma. These therapies (ide-cel and cilta-cel) have been approved for several years. Dana-Farber and other specialized medical centers have the expertise and resources needed to administer these medicines.  

These therapies have shown very positive results in practice, says Dana-Farber hematologic oncologist Omar Nadeem, MD, clinical director of the Myeloma Immune Cell Effector Cell Therapy Program, even in patients who have received many lines of previous treatments. Cilta-cel is approved for use in patients after one prior line of therapy, and ide-cel after two, based on positive results from clinical trials led by Dana-Farber and other experts. 

CAR T-cell therapy might not be appropriate for patients who have disease that is advancing rapidly, or those who might not be able to tolerate the serious side-effects that can accompany CAR T-cell therapy. The therapy also may require extensive time away from home if the patient doesn’t live near a medical center that provides it.  

Bispecific Antibody Therapy: There are also several bispecific antibody therapies approved for relapsed/refractory multiple myeloma. These therapeutics are also showing promising response rates and can be an option for patients who might not be able to tolerate CAR T-cell therapy or for patients who already had CAR T-cell therapy. 

Your Dana-Farber care team can help you determine if one of these options is right for you.  

“It depends on where the patient is in the lifetime of their disease, their health status, and personal logistics. All of that comes into play when we think about the best immunotherapy options for patients,” says Nadeem.  

Next-generation immunomodulatory drugs known as CelMoDs show promise for relapsed/refractory myeloma 

Drugs such as thalidomide, lenalidomide, and pomalidomide, have been integral to standard of care combination therapy for patients with myeloma over the last 10 to 20 years. These drugs leverage cellular recycling systems to make proteins that myeloma cells need disappear through a process called targeted protein degradation. They have potent immunomodulatory effects against myeloma in addition to direct killing of the myeloma cells.  

Now, a next-generation medicine in this broad category, a once-daily pill called mezigdomide, is showing great promise in early clinical trials. In 2023, Richardson and colleagues reported in the New England Journal of Medicine impressive responses to mezigdomide in combination with dexamethasone in patients with relapsed and refractory multiple myeloma which had stopped responding to all currently available therapies, including immune treatments. Phase 3 trials of mezigdomide are now underway.   

Similar work with iberdomide, also a once daily pill and in the CelMoD class, has shown benefit and is moving into the newly diagnosed and early relapse settings. 

Learn more about the history of these medicines in multiple myeloma in Dana-Farber’s Unraveled podcast.  

Efforts continue to expand options for relapsed/refractory myeloma 

Two medicines that had previously been approved within the last 3 years for multiple myeloma in the U.S. have been withdrawn from the U.S. market following their accelerated approvals because initial Phase 3 studies of each drug did not meet rigorous FDA requirements for clinical benefit. These medicines are melflufen and belantamab mafodotin. Many patients treated at Dana-Farber and elsewhere in the US have received these medicines and might wonder about these withdrawals. 

According to Richardson, these drugs are safe and have shown significant benefit to subgroups of patients in clinical trials, as well as in real-world practice. More testing is required to determine where they (or medicines like them) might best fit into myeloma treatment.  

Belantamab mafodotin, an antibody-drug conjugate, is currently available in the context of clinical trials and in an expanded access program for patients in the U.S. Favorable results were reported in recent pivotal phase III combination studies of belantamab mafodotin in combination with bortezomib and dexamethasone (the DREAMM-7 study), and pomalidomide with dexamethasone (the DREAMM-8 trial).  

Melflufen, a potent peptide drug conjugate, is fully approved in Europe and elsewhere, including Asia. Future directions in the US include planned studies of a next generation peptide drug conjugate, as well as continued compassionate use of melflufen as part of combination therapy in selected patients.  

Investigations of new options for newly diagnosed myeloma underway 

With the success of CAR T-cell therapy in patients who have received many lines of treatment, investigators are interested in learning if CAR T-cell therapy might be a good choice for patients immediately after diagnosis. Dana-Farber investigators will be opening a large phase 3 clinical trial comparing induction therapy followed by stem cell transplant to CAR T-cell therapy in newly diagnosed patients to help guide the selection of initial therapies.  

Learn more about treatment for multiple myeloma at Dana-Farber.  

Multiple therapies are in trials for smoldering multiple myeloma 

Multiple myeloma is a cancer that affects the immune system. Smoldering myeloma is a precursor condition that sometimes develops into multiple myeloma. Prior to the transition, the immune system is still healthy and hasn’t been affected by the cancer. 

Dana-Farber experts are interested in learning if immunotherapies might be more effective if given to patients early, as an intervention before smoldering multiple myeloma becomes multiple myeloma. Investigations are underway: 

• In 2023, Nadeem reported early results of phase 2 clinical trial showing that bispecific antibody therapy in patients with smoldering myeloma drove the precursor condition to undetectable levels.  
• The Center for Early Detection and Intervention at Dana-Farber is investigating whether other therapies, including combination therapy and CAR T-cell therapy, might benefit patients with smoldering multiple myeloma that is of high risk of developing into multiple myeloma. 

Learn more about clinical trials for smoldering multiple myeloma at Dana-Farber.