Dr Larry D. Anderson Jr on Updated Phase 2 KarMMa Findings, Implications of COVID-19 for CAR T-Cell Therapy

Findings indicate an overall response rate of 73% for the chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel) in the treatment of relapsed or refractory multiple myeloma, with the safety profile remaining consistent regardless of the number of prior lines of therapy, said Larry D. Anderson Jr, MD, PhD.

Transcript

Can you discuss the long-term data on ide-cel being presented at the 2021 ASCO Annual Meeting?

This is an updated analysis from the KarMMa study presented at ASCO ‘21 that shows longer-term efficacy and safety results in patients treated with ide-cel in the KarMMa trial overall, and broken down by number of prior lines of therapy of 3 vs 4 or more, since the FDA label is requiring at least 4 prior lines of therapy and the study only required 3.

Our results showed a 24.8-month median overall survival in triple class–exposed, relapsed refractory multiple myeloma now at a median follow-up of 24.8 months, the longest follow-up to date for a global clinical trial of CAR T-cell therapy for myeloma.

Overall survival was similar after 3 vs 4 or more prior lines of therapy. And also of note, it was over 20 months for those with extramedullary disease and with triple class refractory. Overall, 128 patients were infused with ide-cel in this study, with a range of 150 to 450 million CAR T-cells infused. These were patients that had received a median of 6 prior lines of therapy, ranging from 3 to 16.

The overall response rate was 73%. Median progression-free survival [PFS] was 8.6 months. This study showed an average response rate that wasn't affected by the number of prior lines of therapy. However, the patients that received the highest target dose of 450 million CAR T-cells did have higher response rates of 81% and the complete response rate was higher at 39% and the median PFS was 12.2 months.

Responses were durable, with a median duration of response of 10.9 months among all ide-cel–treated patients [and] an increase with depth of response to 21.5 months of duration of response for those achieving complete response.

Although 84% of patients in this study experienced some level of cytokine release syndrome, only 6% had grade 3 or higher, and fortunately, only 18% of patients in the study experienced any grade of neurotoxicity, with only 4% experiencing grade 3 and no grade 4 or 5 neurotoxicity.

So, the safety profile in this study was similar regardless of the number of prior lines of therapy [and] remained consistent with longer follow up, with similar rates of infections, second primary malignancies, and no unexpected gene therapy–related toxicities. And based on this study, the ide-cel product has now been FDA approved for patients with relapsed refractory multiple myeloma who have received at least 4 prior lines of therapy.

Were patients given ide-cel during the pandemic? If so, can you describe the protocols and what you have learned? Should patients with refractory multiple myeloma be vaccinated if CAR T-cell therapy is contemplated?

Certainly, we have been giving CAR T-cell [therapy] during the pandemic. We did have a pause for a couple months at the very beginning of the pandemic when we didn't really know which way things were going. So, everything was on hold for a couple months last year, but since then we've been moving forward.

We do have a lot of protocols in place to ensure the safety of our patients. We’ll screen them with a swab for coronavirus before their infusion, before their collection, and then usually we'll admit them to a cell therapy unit where all the other patients are also screened for coronavirus so that these patients don't come down with coronavirus during their period of low immune system.

We will recommend revaccination against coronavirus starting around 3 months out from CAR T-cell therapy. So, even if they've had a prior vaccine before, just because of the possible dysfunction of the residual immunity, we'll recommend repeating that vaccination starting about 3 months out, but certainly if patients are not immediately about to go through their CAR T-cell therapy, just thinking about it in the next few months, then certainly would also recommend going ahead and getting that coronavirus vaccine to build up some immunity that might help protect them during their procedure as well.