KarMMa: Idecabtagene vicleucel in patients with r/r multiple myeloma

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Published: 26 Jun 2020
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Prof Jesús San Miguel - Universidad de Navarra, Pamplona, Spain

Prof Jesús San Miguel speaks to ecancer in an online interview for the virtual EHA 2020 meeting.

He discusses the KarMMa study initial results. KarMMa looks at idecabtagene vicleucel , a BCMA-targeted CAR T cell therapy, in patients with relapsed and refractory multiple myeloma.

Prof Miguel explains the very positive initial results, providing specific response data, and an outline of the toxicity profile.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.
 

The outcome of triple class refractory myeloma patients, those who have failed proteasome inhibitors, immunomodulatory drugs and CD38, is very poor with median progression free survival of approximately 3-4 months. Therefore, we need new targets for these patients and one of these is the BCMA antigen. Here we are going to discuss about ide-cel, a BCMA directed CAR T-cell therapy, that has been tested in a phase I with 33 patients and showed very promising results.

In the current study a total of 128 patients have been included at three different doses – 150, 300 and 450 million cells. These patients were heavily pre-treated, they were clearly refractory patients, they have high tumour burden, they have 39% of the patients extramedullary disease, 35% of the patients had high risk cytogenetics, 84% of the patients were triple refractory, 26% were double refractory. Interestingly, the vast majority of these patients, 88%, required bridging therapy before the CAR T-cell infusion indicating the aggressiveness of the disease and only 4% of the patients responded.

What were the results in these patients? The overall response rate was 73% including one-third of the patients achieving a complete response. When you analyse the response at the maximum dose, 450, the response rate increased to 82% and almost 40% achieved a complete response. The duration of response was 10.7 months for the global series of patients.
What about the progression free survival? The progression free survival for the total series of the 128 patients was 8.8 months but increased to 12.1 months in those patients receiving 450 million. Interestingly, also the depth of response correlated with progression free survival – in patients that achieved a complete response the progression free survival was 20 months. Overall survival is premature and most of the patients are still alive.

Regarding the safety profile, treatment was really well tolerated. CRS grade 3 and neurotoxicity were observed in less than 6% of the patients at the maximum dose of 450 million. Two-thirds of the patients required tocilizumab, 22% of the patients required corticosteroids. The most common side effect was neutropenia and thrombocytopenia that required between 2-3 months to recover. Only five deaths were observed within the first period of treatment and two of them were attributed to myeloma progression and only one to CRS.

Therefore we can say in summary that we have now a new standard of care for myeloma patients triple refractory that can benefit from a CAR T that is associated with a good safety profile and high efficacy. More than 80% of the patients would respond, a high proportion of these patients will achieve a complete response; complete response is associated with over 20 months progression free survival. Therefore I think we can congratulate all doctors and patients and families for this new opportunity.