Which Novel Drug Classes Hold Promise in Multiple Myeloma Therapy?

In a conversation with CancerNetwork^®, Natalia Neparidze, MD, highlighted various drug and treatment classes that may impact the multiple myeloma paradigm. Beyond CAR T-cell therapies and bispecific antibodies, she detailed the cereblon E3 ligase modulator (CELMoD) agents and trispecific antibodies that represent “exciting opportunities” in the space.

Neparidze, an associate professor of Internal Medicine (Hematology) at Yale School of Medicine, said that CELMoDs like iberdomide and mezigdomide may be “super powerful drugs” for patients with multiple myeloma, highlighting their oral availability as a promising feature. She also described the ongoing development of trispecific antibodies, which have leveraged targets like BCMA and GPRC5D to yield responses in heavily pretreated populations with refractory disease. According to Neparidze, FcRH5 is emerging as another potentially active target, with agents like cevostamab undergoing evaluation in clinical trials.

Transcript:

I will start with some of the small molecules, namely the CELMoDs. There are many [in] this class, primarily iberdomide, which may very soon receive FDA [approval] in combination with CD38 monoclonal antibodies, as well as mezigdomide and many others that are working through the IKAROS [IKZF1]/AIOLOS [IKZF3] CELMoD mechanism, [which] are super powerful drugs. These are orally available, and that’s very promising.

Some of the novel, dual-targeting trispecific antibodies represent big breakthroughs. There are many trispecific antibodies in development right now. They do have BCMA and GPRC5D targets, and these achieve nearly 100% overall response rates in heavily pretreated, refractory patients. Additionally, there’s much more to learn in terms of immune dissection; the FcRH5 target is emerging as another potentially highly active target, [for] which we now have cevostamab in clinical trials and is hopefully progressing through. [There are also] many others. Eventually, immune editing and cell therapies—which are not traditional CAR-Ts, but perhaps in vivo CAR-Ts or allogenic CAR-Ts—are all in development. There’s a lot of room for improvement and lots of exciting opportunities in that realm.