Larry D. Anderson, Jr, MD, PhD

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.


 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?

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?

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.

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Larry D. Anderson, Jr, MD, PhD, discusses the rationale behind using chimeric antigen receptor T-cell therapy in relapsed/refractory multiple myeloma, data from the KarMMa trial, and other trials investigating this treatment. 

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 updated results of the KarMMa trial in relapsed/refractory multiple myeloma.

These long-term data for idecabtagene vicleucel (ide-cel, bb2121) demonstrated deep and durable remissions in a majority of patients on the trial, according to Anderson. Patients with relapsed/refractory multiple myeloma on this trial had a median of 6 prior lines of therapy. With a median 24.8-month follow-up, the median overall survival on trial was 24.8 months also. For the 128 patients, there was a 73% overall response rate, and the median progression-free survival (PFS) was 8.6 months. Those who received the target dose of 450 million chimeric antigen receptor T cells had a median PFS of 12.2 months.

Anderson says another notable topic was the FDA label for ide-cel requires patients to have 4 prior lines of therapy while the trial only required 3 prior lines of therapy. One of the study analyses looked at efficacy for patients who received 3 prior lines versus 4 or more. There was not a significant difference in outcomes for these 2 groups.

Larry D. Anderson, Jr, MD, PhD, discusses the updated results of the KarMMa trial in relapsed/refractory multiple myeloma.

Larry D. Anderson, Jr, MD, PhD | Authors

Articles

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

Updated KarMMa Trial Results Show Durable Responses in Multiple Myeloma