Jesus G. Berdeja, MD

Jesus G. Berdeja, MD, director of multiple myeloma research at Sarah Cannon Research Institute and hematology specialist at Tennessee Oncology, discusses the potential of chimeric antigen receptor (CAR) T-cell therapy to be approved for earlier lines of treatment in multiple myeloma.

Ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) have been approved for patients with relapsed/refractory multiple myeloma following 4 lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. Both of these CAR T-cell therapies have strong efficacy in this setting, and Berdeja says there are studies underway that could support earlier usage.

Additional trials such as the phase 2 KarMMA-2 trial (NCT03601078) of ide-cel and the phase 2 CARTITUDE-2 trial of cilta-cel (NCT04133636) are exploring treatment in patients who have received 1 to 3 lines of therapy. According to Berdeja, patients with high-risk disease could benefit greatly from CAR T-cell therapy early in the course of treatment, so CAR T-cell therapy could have a place as a frontline option.

Berdeja says that adopting these therapies is especially significant for certain populations that will not respond to alternative therapies. He also hopes that CAR T-cell therapy will be more readily available so patients with aggressive disease can receive it more easily.

Right now, the commercial CAR Ts, both ide-cel and cilta-cel, are approved for patients who've had at least 4 prior lines of therapy—who have had a PI, an immunomodulatory agent, and an anti-CD38 antibody—so relatively late in the course of treatment. I think they'll have an immediate impact in the relapsed/refractory setting as they are now. But definitely studies are ongoing and trying to move these therapies earlier in the course of treatment.

 There are several studies, both KarMMA and CARTITUDE, ongoing in patients with 1 to 3 prior lines of therapy, comparing it to standard of care. There's actually a significant need in the high-risk population, even from the first line of therapy and there are actually studies ongoing in that high-need population even early on.

But beyond that, there are actually now studies also looking at CAR T cells in the frontline setting. So, I think the future for CAR Ts is that these will be sort of implemented into the treatment paradigm of myeloma from the very beginning, and definitely in at least certain patient populations. And hopefully, they will be used better than where we are now, where oftentimes patients’ myeloma is so aggressive that they can't get to the CAR T cells. There is a potential that it could be used in every aspect of myeloma, again, depending on the availability and some of these logistical challenges.

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Jesus G. Berdeja, MD, discusses the potential of chimeric antigen receptor T-cell therapy to be approved for earlier lines of treatment in multiple myeloma. 

CAR T Cells Have Potential as Earlier-Line Therapy for Multiple Myeloma

Jesus G. Berdeja, MD, director of multiple myeloma research at Sarah Cannon Research Institute and hematology specialist at Tennessee Oncology, discusses the results of the CARTITUDE-1 trial (NCT03548207) for chimeric antigen receptor (CAR) T-cell therapy with the newly-approved agent ciltacabtagene autoleucel (cilta-cel; Carvykti) for relapsed/refractory multiple myeloma.

CARTITUDE-1 treated 97 patients with a median of 6 prior lines of therapy for multiple myeloma with 0.75 x 106 cells per kg, which Berdeja says is low compared with the dose of idecabtagene vicleucel (ide-cel; Abecma). At 18 months median follow-up, there was an overall response rate (ORR) of 98% and a stringent complete response (sCR) rate of 80.4%, with 94.8% of patients achieving a very good partial response or better. Berdeja says these results for a heavily pretreated population are comparable with those of frontline treatment for patients with multiple myeloma.

Progression-free survival (PFS) was not reached at 2 years, suggesting that the median PFS will be over 2 years, while Berdeja says patients like this population normally have a PFS of only a few months. Considering both the depth of response and duration of response, he says these results are very impressive.

 in February 2022 for patients with relapsed/refractory multiple myeloma who had received 4 or more prior therapies including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.

CARTITUDE-1 is the study for cilta-cel in relapsed/refractory patients with [multiple] myeloma. These were heavily pretreated patients with a median lines of therapy of 6. These patients underwent treatment with a relatively low dose of CAR T [cells] compared to other products. I think it was point 0.75 x 106 per kg, which is roughly about 50 to 70 million CAR T cells compared to ide-cel, for example, which went up to 450 million CAR T cells. So, the results are spectacular and unprecedented.

Again, in this relapsed/refractory population, the expectation for new drugs is that if we see a response rate of 20% to 30%, that that's an active drug. That's often [why] drugs in the past have been approved in [multiple] myeloma.So, the overall response rate of 98% seen with cilta-cel is quite impressive. Those are the kind of responses that we see in the frontline population. And furthermore, it was the depth of response that was even more impressive, with almost 80% of patients having complete remission or better. Again, those are very impressive results.

 I think what's even more impressive thus far is that when we looked at the 2-year mark, the median PFS had not been reached, which tells us that the median PFS will be over 2 years. Again, something that we never see this late in patients with myeloma. These patients in general have a median PFS of just a few months. So, there’s lot more to come from this trial as it becomes more mature, but that's what's making this very impressive—not only the response rates, the depth of the response, but the durability of those responses.

Jesus G. Berdeja, MD, director of multiple myeloma research at Sarah Cannon Research Institute and hematology specialist at Tennessee Oncology, discusses the results of the CARTITUDE-1 trial for chimeric antigen receptor T-cell therapy with the newly-approved agent ciltacabtagene autoleucel for relapsed/refractory multiple myeloma. 

Cilta-cel Shows Deep and Durable Responses for R/R Multiple Myeloma

Jesus G. Berdeja, MD, director of Myeloma Research at Sarah Cannon Research Institute, discusses the findings from the phase 2 results of ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) as treatment of patients with relapsed/refractory multiple myeloma in the CARTITUDE-1 study (NCT03548207).

Researchers were gratified by the results seen in this study, says Berdeja, especially in regard to the response rates. The objective response rate was 97% with 57% of patients achieving a stringent complete response and 92% a partial response or better.

According to Berdeja, the median progression-free survival had not been reached yet, but at 12-months, 76.6% of patients remained in remission in the study.

Jesus G. Berdeja, MD, discusses the findings from the phase 2 results of ciltacabtagene autoleucel as treatment of patients with relapsed/refractory multiple myeloma in the CARTITUDE-1 study.

CARTITUDE-1 Study Demonstrates Promising Response Rates in Relapsed/Refractory Myeloma

Jesus G. Berdeja, MD, director of Myeloma Research, senior investigator, Hematologic Malignancies Principal Investigator, Sarah Cannon Research Institute, discusses a phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed or relapsed/refractory multiple myeloma.


Jesus G. Berdeja, MD | Authors

Articles

CAR T Cells Have Potential as Earlier-Line Therapy for Multiple Myeloma

Cilta-cel Shows Deep and Durable Responses for R/R Multiple Myeloma

CARTITUDE-1 Study Demonstrates Promising Response Rates in Relapsed/Refractory Myeloma

Combination of Panobinostat and Carfilzomib in Relapsed or Relapsed/Refractory Multiple Myeloma