Rationale, Data, and Future of Using Ide-Cel CAR T-Cell Therapy

Larry D. Anderson, Jr, MD, PhD, a hematologist/oncologist at the Harold C. Simmons Comprehensive Cancer Center and an associate professor in UT Southwestern Medical Center’s Department of Internal Medicine, Division of Hematology/Oncology, discusses the rationale behind using chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory multiple myeloma, data from the KarMMa trial, and other trials investigating this treatment.

The KarMMa trial (NCT03361748) looked at idecabtagene vicleucel (ide-cel, bb2121) in the relapsed/refractory setting and showed promising efficacy and safety. It was given after at least 3 lines of therapy. However, the ongoing trials KarMMa-2 (NCT03601078) and KarMMa-3 (NCT03651128) are investigating whether ide-cel works as treatment after less than 3 lines of therapy.
Transcription:

0:08 | The reason we conducted the KarMMa study was that historically patients with relapsed/refractory multiple myeloma [who] have been exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies have a very poor prognosis, with the expected progression-free survival with other approved therapies in the 2- to 4-month range, overall survival less than a year, and overall response rates in the 25% to 31% range. So more effective therapies are desperately needed in this area of unmet need.

What were the important efficacy and safety data in the KarMMa trial?

0:43 | Certainly, we do see differences in patients that achieve a complete remission. So those patients tend to have a lot longer duration of response. So those that had a complete response had a duration of response of 21.5 months.

We wanted to show that the safety outcomes were also similar to previous reports and not showing anything new with later follow-up. So we can still show that—although the majority of patients experience some level of a [adverse] effect called cytokine release syndrome—about 84% of them had some level of cytokine release syndrome, but only about 6% had severe cytokine release syndrome, so very uncommon to have severe. Then also we wanted to have further follow-up on the rates of neurotoxicity, which can be seen with CAR T-cell therapy. Fortunately, only 18% of the patients in this study experienced any grade of neurotoxicity, only 4% had grade 3 neurotoxicity, and no patients experience grade 4 or 5 neurotoxicity. So essentially, we show that the safety was similar to previous reports. We're not seeing any long-term unexpected [adverse] effects, no increase, unexpected second primary malignancies, and no gene therapy–related toxicities.

How will this treatment be studied further in this setting?

2:22 | We have trials looking at patients who have had 2 lines of therapy called the KarMMa-3 study. We also have a trial looking at patients who have had 1 prior line of therapy with an early relapse called the KarMMa-2 study. Then more recently, we opened a study for frontline therapy. The same ide-cel CAR T-cell product for patients with high-risk chromosome myeloma. So instead of a stem cell transplant, they will be receiving ide-cel CAR T-cell therapy. We have no data from those studies yet but we're excited to see the outcomes.