Continued Development of T-Cell–Redirecting Therapies Remains at the Heart of Myeloma Research

Joshua Richter, MD

The treatment landscape for multiple myeloma continues to advance with the expansion of T-cell–redirecting therapies, according to Joshua Richter, MD, who added that these agents have built upon the era of treatment options such as immunomodulatory drugs (IMiDs), proteasome inhibitors, and anti-CD38 monoclonal antibodies.

In the second part of an interview with OncLive® during Multiple Myeloma Awareness Month—observed annually in March—Richter discussed the evolving therapeutic landscape of multiple myeloma, the role of BCMA-targeted therapies and other T-cell–redirecting treatments, and key considerations for optimizing treatment sequencing as additional agents continue to emerge. In the first part of the interview, Richter highlighted the importance of symptom recognition and understanding precursor conditions in multiple myeloma.

Richter is an associate professor of medicine in the Division of Hematology and Medical Oncology at the Tisch Cancer Institute, as well as director of Multiple Myeloma at the Blavatnik Family-Chelsea Medical Center at Mount Sinai in New York, New York.

OncLive: What should clinicians understand about multiple myeloma and its treatment paradigm in 2025?

Richter: The way I think about approaching myeloma is that there have been three epochs of treatment. The first was the old days of chemotherapy. These were the days of oral melphalan; vincristine plus doxorubicin and dexamethasone; and cyclophosphamide. [Chemotherapy regimens] didn't do all that well. Then we moved into the era of novel therapies [using] IMiDs, proteasome inhibitors, and even [anti-CD38] monoclonal antibodies.

Now, in the last couple of years, we started to embrace the third epoch: the T-cell–redirection age, where we're using bispecific antibodies and CAR T-cell therapies. A lot of these therapies have been relegated to academic centers; [however], we're starting to optimize these [therapies] so that they can be administered anywhere. At the end of the day, bispecific antibodies—an off-the-shelf, T-cell–redirecting therapy—are going to change the way we approach myeloma.

Community oncologists originally were all about chemotherapy. When immunotherapy and things like checkpoint inhibitors came along, I think there was a little apprehension. However, now [when you] go to any community center, many patients [with cancer] are getting [immune checkpoint inhibitors] like ipilimumab [Yervoy], nivolumab [Opdivo], and pembrolizumab [Keytruda]. Bispecific antibodies are also working their way into [the treatment of] solid tumors, [such as] the approval of tarlatamab-dlle [Imdelltra], a bispecific antibody, for [extensive-stage] small cell lung cancer. We're on the precipice of moving T-cell redirection into the hands of everyone, [meaning] that no matter where you are in the country, [patients with multiple myeloma and other tumors] could get access to these amazing new treatments.

What are the latest treatment advancements available in 2025 for multiple myeloma, particularly in CAR T-cell therapy and other therapeutic strategies?

In 2025, the buzzword is BCMA. BCMA, also known as CD269, is located on all myeloma cells, and BCMA-targeted therapy is the new modality for treating relapsed disease.

Now, at the moment, there are 4 FDA-approved BCMA-targeted agents: 2 CAR T-cell therapies [ciltacabtagene autoleucel (Carvykti) and idecabtagene vicleucel (Abecma)] and 2 bispecific antibodies [teclistamab-cqyv (Tecvayli) and elranatamab-bcmm (Elrexfio)]. However, by the end of [2025], we are likely to have 1 additional BCMA-targeting bispecific antibody [approved with linvoseltamab (REGN5458)].

We also have belantamab mafodotin [Blenrep], which is a BCMA-targeting antibody-drug conjugate [ADC] previously approved, then taken off the market. [A biologics license application] has been refiled [seeking the approval of belantamab mafodotin] in combination with [bortezomib (Velcade) and dexamethasone and in combination with pomalidomide (Pomalyst) and dexamethasone].

Therefore, the likelihood is that we're going to start off 2025 with 4 FDA-approved BCMA-targeted treatments and end [the year] with 6 or more.

We like to think of the pecking order [among BCMA-targeted therapies] as CAR T-cell therapy as probably the best, then bispecific antibodies, then ADCs. However, at the end of the day, I live by the adage, never let perfection be the enemy of the good. [For] some patients, a CAR T-cell therapy is not appropriate because it's too aggressive or they don't want to be hospitalized. The same thing may be true for a bispecific [antibody], where [the patient] may not have access to it, and an ADC may be the best [option]. The reality is that [each] of these modalities has provided unprecedented response rates, and they need to become part of our regular armamentarium [in multiple myeloma].

What advice would you give to colleagues on selecting the most appropriate agent for different patient populations?

My advice is that myeloma is a chess game. It doesn't matter what the next move is; rather, how does this move affect [subsequent moves]? For example, we know that all else being equal, it's better to give a CAR T-cell therapy [before] a bispecific [antibody] vs a bispecific followed by CAR T-cell therapy. Once you're about to start dipping your toe into the immunotherapies such as the BCMA-targeted bispecific antibodies, the GPRC5D-targeted bispecifics, the ADCs, and the CAR T-cell therapies, [providers need to] make sure to contact a myeloma expert at one of the amazing myeloma centers in this United Stated to have that conversation. You want to make sure that if you're going to give a bispecific [antibody that you consider how it could] alter a potential CAR T-cell therapy response for an eligible patient [in the future]. Having that interchange between community and academic [clinicians] is key as far as which moves should be made, where, when, and how.