CAR T-Cell Therapy Significantly Impacts R/R Multiple Myeloma

Targeted Oncology: Please describe the phase 3 KarMMa-3 study (NCT03651128).

ABDULLAH KHAN, MBBS: This was our first phase 3 B-cell maturation antigen [BCMA] chimeric antigen receptor [CAR] T-cell therapy study in patients who had 2 to 4 prior lines of therapy.¹ Patients were randomly assigned to either idecabtagene vicleucel (ide-cel; Abecma) or [a selection of standard regimens chosen by the physician]. The [standard regimens were] specified as they could either get bridging therapy with that therapy until [the patient’s] CAR T-cells were manufactured and sent back to the institution. The primary end point was progression-free survival [PFS], and these data were published in the New England Journal of Medicine.¹

What prior regimens did the patients on this study receive?

There were European and North American patients [recruited for the study, so this impacted the use of prior therapy] as we saw thalidomide and other therapies like that used previously.¹ Generally, there was a very high use of immunomodulatory drugs, proteasome inhibitors, and a lot of these patients also had transplants, but 95% were refractory to daratumumab [Darzalex].¹ These were standard patients with multiple myeloma [who had a] second relapse.

Abdullah Khan, MBBS​

Assistant professor, Division of Hematology

The Ohio State University

How do you consider treatment for patients with relapsed/refractory multiple myeloma referred to you?

Presumably, [the patient was] referred to us because they're relapsing on their last regimen. We can probably come up with a good bridging regimen, but for some patients, where they're running out of options, [we need to just give them] something. But I don't think that’s [the case as much] anymore; I think we're able to salvage the patients a little bit better. Now, if [the patient's disease burden is] growing while we're waiting for their CAR T-cells, that's probably a bad outcome anyways. But if you're able to somehow decrease that disease burden [ahead of time] then the patient will do better, so don't go into CAR T-cell therapy [when the patient's disease burden is] increasing—have some disease control first.

What were the main efficacy results of the KarMMa-3 study?

In the final PFS analysis...the median PFS with [ide-cel] was 13.8 months [range, 11.8-16.1] compared with [the standard regimen arm] at 4.4 months [range, 3.4-5.8], which were excellent results and had a HR of 0.49 [95% CI, 0.38-0.63].² I don't think we have the same [length] observed in lymphoma…but it’s a pretty good curve compared with the standard regimen arm. I think it just needs a longer follow-up.

The depth of response was also significantly better with ide-cel vs chemotherapy [with an overall response rate of] 71% [95% CI, 66%-77%] vs 42% [95% CI, 34%-51%], respectively. Then the stringent complete response rates [sCR] of 41% [in the ide-cel arm were greater than the 5% in the standard regimen arm]. So, the depth and the quality of the response with CAR T-cell therapy is significantly better than [the standard regimens]. This also included achieving better minimal residual disease [MRD] negative CR rates [as well]. The researchers [had a smaller number of patients to] check, but a 35% [95% CI, 28%-42%] MRD negative CR rate vs 2% [95% CI, 0%-5%] for patients with 2 to 4 prior lines of therapy [is a] pretty good rate of attaining MRD negativity.²

REFERENCES:

1. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614

2. Rodriguez-Otero P, 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(1):1028. doi:10.1182/blood-2023-178933