Lonial Reviews 2023 Highlights for Multiple Myeloma, Forecasts 2024 Research Interests

Sagar Lonial, MD, FACP

Updated data from phase 3 trials evaluating ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma), which continued to show improved progression-free survival (PFS) for patients with relapsed or refractory multiple myeloma vs the standard-of-care (SOC), represent one of the highlights of 2023 for the field, according to Sagar Lonial, MD, FACP.

Data presented at the tail end of the year at the 65th ASH Annual Meeting and Exposition from the final PFS analysis of the phase 3 KarMMa-3 trial (NCT03651128) revealed that the median PFS was 13.8 months in the ide-cel arm (n = 254) vs 4.4 months in the SOC arm (n = 132; HR, 0.49; 95% CI, 0.38-0.63) at a median follow-up of 30.9 months for patients with triple-class–exposed relapsed or refractory multiple myeloma.¹ In addition to the significant benefit observed regarding PFS with CAR T-cell therapy vs SOC in KarMMa-3, data published in the New England Journal of Medicine from the phase 3 CARTITUDE-4 trial (NCT04181827) showed that treatment with cilta-cel resulted in a significantly lower risk of disease progression or death vs SOC for patients with lenalidomide (Revlimid)-refractory multiple myeloma. The median PFS was not reached in the cilta-cel arm (n = 208) compared with 11.8 months in the SOC arm (n = 211; HR, 0.26; 95% CI, 0.18-0.38; P < .001).²

“Referral even at the time of first relapse so that you get on the agenda of the CAR T-cell center and receive guidance on what to do next and when to see the patient back [is needed],” Lonial, the chief medical officer at Winship Cancer Institute, said. “Early visits with a CAR T center are going to remain critically important.”

In an interview with OncLive®, Lonial, who is also professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine, detailed additional agents of interest outside CAR T-cell therapies including the recently approved agents elranatamab-bcmm (Elrexfio) and talquetamab-tgvs (Talvey).

OncLive: What were key trials that impacted clinical practice for multiple myeloma in 2023 and what would a community oncologist take away from these trials?

Lonial: There were a number of trials that came out in the past 12 to 18 months that are driving current treatment practice. The trials comparing CAR T cells with standard therapies in earlier lines of therapy—CARTITUDE-4 and KarMMa-3—are important studies that are setting the stage for bringing CAR T-cell therapy earlier in the treatment paradigm.

Seeing the updated data on the T-cell engagers elranatamab and teclistamab was important in the past year [regarding] how to use these agents in an effective way. The other new targeted [agent] we got in the past year was talquetamab. Seeing updates of the MonumenTAL trials were some of the big highlights of where we were up until the ASH Meeting in 2023.

Treating a patient [who experiences] late relapse is more complicated now than it was 3 years ago [because] we have more options targeting BCMA, options targeting GPRC5D, and [we are] getting comfortable with either referring patients for CAR T-cell [therapy] earlier or referring for T-cell engager therapy earlier. [These] are things that need to be top of mind unless your practice can sustain giving patients T-cell engagers from the get-go or sustain CAR T cells on their own, depending upon the kind of practice setting you’re in. Those are key parts of improving outcomes for patients with myeloma.

How are you incorporating approvals for elranatamab or talquetamab into care for relapsed/refractory disease?

These treatments allow an off-the-shelf approach for management of relapsed and refractory myeloma. CAR T-cell therapies are great, but of the people that you want to give a CAR T-cell therapy to, maybe half of them [receive one], whereas talquetamab, elranatamab, and even teclistamab are off the shelf. There are some logistical challenges to giving them if you’re in a community practice, but in general, they can be done within a week, which from a patient perspective is a whole lot easier than waiting 6 or 8 weeks and figuring out what to do from a CAR T perspective.

What novel approaches are you investigating in your current research?

Our question is how do you take these individual treatment approaches and put them together in a comprehensive treatment plan? We’ve gotten good at giving continuous therapy in myeloma, but we need to get away from the continuous therapy model and get to defined duration of therapy guided by depth of response—things like minimal residual disease might be helpful. The question I always get from patients is: Can we replace transplants with CAR T cells? I don’t know that we can right now so transplants need to remain an important part of their treatment approaches. But is there a way to put our best drugs and best targets together so [we] can combine them and ultimately cure [patients with] the disease and stop treatment?

What agents are you keeping your eye on in the hematology space in 2024?

The targets that we’re excited about are the next-generation BCL2 inhibitors. We saw data at the ASH meeting from compounds [such as] sonrotoclax, [which] appears to be more potent than venetoclax [Venclexta] with a better adverse effect profile. That is a drug and target we’re very interested and excited about.

Another T-cell engager, cevostamab, which targets FcRH5, is a drug that we’re excited about.

The new cereblon E3 ligase modulatory drugs iberdomide [CC-220] and mezigdomide [CC-92480] are drugs we’re very excited about. They’re more potent than lenalidomide and pomalidomide [Pomalyst] and seem to have a better safety profile as well. Those are the sort of targets that we’re excited about.

References

1. Otero PR, Ailawadhi S, Arnulf B, et al. Idecabtagene vicleucel (ide-cel) versus standard (std) regimens in patients (pts) with triple-class–exposed (tce) relapsed and refractory multiple myeloma (RRMM): updated analysis from KarMMa-3. Blood. 2023;142(suppl 1):1028. doi:10.1182/blood-2023-178933
2. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379