Jesus Berdeja, MD, director, Multiple Myeloma Research, Tennessee Oncology, discusses the evolving guidelines regarding the use of CAR T-cell therapy in patients with multiple myeloma.

The current guidelines for CAR T-cell therapy administration in patients with multiple myeloma state that patients must have received a minimum of 4 prior lines of therapy, Berdeja begins. However, notable advancements have emerged through 2 phase 3 trials: the KarMMa-3 (NCT03651128) and CARTITUDE-4 (NCT04181827) trials, which evaluated idecabtagene vicleucel (Abecma; ide-cel) and ciltacabtagene autoleucel (cilta-cel; Carvykti), respectively, in earlier stages of treatment, he explains. The results of these trials have demonstrated the superiority of CAR T-cell therapy compared with other multiple myeloma therapies, according to Berdeja. KarMMa-3 enrolled patients who had received 2 to 4 prior lines of therapy, most of whom had been exposed to anti-CD38 treatments. Contrarily, CARTITUDE-4 evaluated patients who had received 1 to 3 prior lines of therapy, with a lower proportion having been previously exposed to anti-CD38 therapies, Berdeja emphasizes. Both trials revealed the effectiveness of CAR T-cell therapy over the standard treatment regimen, he states.

Oncologists anticipate that the FDA will revise the indication for CAR T-cell therapies for patients with multiple myeloma, potentially moving them into earlier stages of treatment, Berdeja expands. The specific indications remain to be defined, but there is a possibility that the stipulation regarding the number of prior lines of therapy may be lifted, he explains. This development would be important because it would address the concerns of many patients who may struggle to endure 4 lines of therapy before accessing CAR T-cell treatment, especially when CAR T-cell therapy has proven to be a superior regimen, Berdeja says.

Moreover, ongoing research efforts are now focusing on incorporating CAR T-cell therapies and bispecific antibodies into the frontline setting for patients with multiple myeloma, Berdeja continues. The primary population of interest in this research includes high-risk patients who have historically not responded favorably to standard therapies, Berdeja says. Furthermore, randomized phase 3 trials are beginning to explore the possibility of using CAR T-cell therapies beyond the high-risk population in patients who are either eligible or ineligible for transplantation.

Considering these developments, it is possible that in coming years, CAR T-cell therapies and bispecific antibodies could become integrated into the frontline treatment setting for patients with multiple myeloma, potentially reshaping the therapeutic landscape, Berdeja concludes.

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Jesus Berdeja, MD, director, discusses the evolving guidelines regarding the use of CAR T-cell therapy in patients with multiple myeloma.


Dr Berdeja on the Evolving Use of CAR T-Cell Therapy in Multiple Myeloma

Jesus G. Berdeja, MD, director, Myeloma Research, Sarah Cannon Research Institute, discusses the investigation of BMS-986393 in patients with relapsed/refractory multiple myeloma.

BMS-986393 is a GPRC5D-directed CAR T-cell therapy. Interim results from the dose-escalation portion of a phase 1 trial (NCT04674813) examining the product were presented at the 2022 ASH Annual Meeting.

Patients on the trial were administered BMS-986393 across 5 dose levels, ranging from 50 x 10

 CAR T cells, Berdeja explains. Among patients evaluable for efficacy (n = 19), BMS-986393 elicited an overall response rate of 89.5%, including a complete response rate of 47.4%, Berdeja says.

Regarding safety, any-grade neutropenia occurred in 66.7% of patients, Berdeja notes. Among non-hematologic treatment-emergent adverse effects, any-grade cytokine release syndrome (CRS) was reported in 63.6% of patients; however, only 6.1% of patients experienced grade 3/4 CRS, Berdeja concludes.

Jesus G. Berdeja, MD, discusses the investigation of BMS-986393 in patients with relapsed/refractory multiple myeloma.

Dr Berdeja on the Safety and Efficacy of BMS-986393 in R/R Multiple Myeloma

Jesus G. Berdeja, MD, the director of Multiple Myeloma Research at Sarah Cannon Research Institute, discusses the dosing of the investigational CAR T-cell product JNJ-4528 in patients with ​relapsed/refractory multiple myeloma.

The median administered dose of JNJ-4528 in the ​phase 1b/2 CARTITUDE-1 trial was 0.72 x 106 CAR + viable T cells/kg,which is lower than other available CAR T-cell products, says Berdeja.

With this dosing strategy, a 70 kg patient would receive about 50 million CAR T cells, explains Berdeja. Although additional information is needed, making fewer CAR T cells may lead to less manufacturing failures.

Moreover, data from the ​CARTITUDE-1 trial showed that the ​median time to onset of cytokine release syndrome (CRS) was 7 days after receiving JNJ-4528. Comparatively, CRS can be observed immediately after infusion with other ​CAR T-cell products, Berdeja concludes.

Jesus G. Berdeja, MD, discusses the dosing of the investigational CAR T-cell product JNJ-4528 in patients with ​relapsed/refractory multiple myeloma.

Dr.  Berdeja on Dosing JNJ-4528 in Relapsed/Refractory Multiple Myeloma

Jesus G. Berdeja, MD, the director of Multiple Myeloma Research at Sarah Cannon Research Institute, discusses next steps for the phase 2 CARTITUDE-1 study with JNJ-4528 in relapsed/refractory myeloma.

The phase 1b/2 CARTITUDE-1 trial enrolled patients with relapsed/refractory multiple myeloma and treated them with the BCMA-targeted CAR T therapy JNJ-4528. The second phase of the study is fully enrolled, says Berdeja. The goal is to combine the data observed with the agent from both phases of the trial to determine its efficacy in this patient population, adds Berdeja. Although this was a phase 1b trial, it was not a dose-escalation trial, clarifies Berdeja. The dose used in the phase 2 portion (0.73x106 CAR plus viable T cells/kg) was the same dose used in the LEGEND trials. The patient population should be fluid, and therefore, it will be the same dose for both phases of the trial.

Data from the phase 2 portion of the trial are highly anticipated, along with longer-term results, says Berdeja. The hope is that the data will reveal how durable responses to the agent will be, although the results that have been seen so far are very encouraging, adds Berdeja.

breakthrough therapy designation by the FDA

, and Berdeja is hopeful that it will be one of the first candidates to obtain FDA approval for patients with relapsed/refractory multiple myeloma. Phase 2 and 3 studies are examining this product in earlier lines of therapy, including high-risk populations, potentially asfrontline consolidation, concludes Berdeja.

Jesus G. Berdeja, MD, discusses next steps for the phase 2 CARTITUDE-1 study with JNJ-4528 in relapsed/refractory myeloma.


Dr. Berdeja on Next Steps With JNJ-4528 in Relapsed/Refractory Myeloma

Jesus G. Berdeja, MD, the director of Multiple Myeloma Research at Sarah Cannon Research Institute, discusses updated safety results from the ongoing phase 1b/2 CARTITUDE-1 trial (NCT03548207) with the CAR T-cell therapy JNJ-4528 in multiple myeloma.

In the study, neurotoxicity was rare; only 1 patient reported an event that was grade 3 or higher in severity, Berdeja says. Significant cytopenias were also observed with JNJ-4528, including neutropenia and thrombocytopenia, although most events resolved within 60 days, says Berdeja. All-grade upper respiratory tract infections were reported in 31% of the patients, however, none of these infections were unexpected, adds Berdeja.

Additionally, results showed a 100% overall response rate with the product, which included a stringent complete response rate of 86% and very good partial response rate of 97% at a median follow-up of 11.5 months, explains Berdeja.

Finally, 16 patients with a CR achieved minimal residual disease (MRD)–negative disease status. Of those patients, 81% were MRD negative at 10-5 or better and 69% were MRD negative at 10-6. The estimated progression-free survival rate at 9 months was 86%, concludes Berdeja.

Jesus G. Berdeja, MD, discusses updated safety results from the ongoing phase 1b/2 CARTITUDE-1 trial (NCT03548207) with the CAR T-cell therapy JNJ-4528 in multiple myeloma.

Dr. Berdeja on Updated CARTITUDE-1 Results With JNJ-4258 in Multiple Myeloma

Jesus G. Berdeja, MD, director of Myeloma Research, principal investigator, Sarah Cannon Research Institute, discusses the FDA approval of frontline daratumumab (Darzalex) in combination with bortezomib (Velcade), melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).

Jesus G. Berdeja, MD

Articles

Dr Berdeja on the Evolving Use of CAR T-Cell Therapy in Multiple Myeloma

Dr Berdeja on the Safety and Efficacy of BMS-986393 in R/R Multiple Myeloma

Dr. Berdeja on Dosing JNJ-4528 in Relapsed/Refractory Multiple Myeloma

Dr. Berdeja on Next Steps With JNJ-4528 in Relapsed/Refractory Myeloma

Dr. Berdeja on Updated CARTITUDE-1 Results With JNJ-4258 in Multiple Myeloma

Dr. Berdeja on FDA Approval of Frontline Daratumumab Plus VMP in Multiple Myeloma