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SOHO 2024 | Will CAR-T be best when used in early relapse in myeloma?
Krina Patel, MD, MSc, The University of Texas MD Anderson Cancer Center, Houston, TX, outlines the growing body of evidence suggesting that CAR T-cell therapy should be moved into earlier lines of treatment in multiple myeloma (MM) to improve patient outcomes. Dr Patel highlights that both data from the KarMMa-3 (NCT03651128) and CARTITUDE-4 (NCT04181827) trials support this, as well as discussing the logistical challenges associated with treating patients with CAR-T later down the line when they have relapsed/refractory (R/R) disease, which proves difficult to control. This interview took place at the Twelfth Annual Meeting of the Society of Hematologic Oncology (SOHO 2024) congress in Houston, TX.
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Transcript
So I think CAR-T out of everything we’ve ever tested in myeloma has had the best responses – the best overall response, the best depth of response, the best MRD undetectability, as well as progression-free survival for patients with relapsed/refractory disease. Now, we have early-line trials – we have two trials with KarMMa-3 as well as CARTITUDE-4, that were done in a randomized Phase III fashion, where they were against standard of care treatment versus the CAR-T, and both of them significantly better PFS and overall response rate...
So I think CAR-T out of everything we’ve ever tested in myeloma has had the best responses – the best overall response, the best depth of response, the best MRD undetectability, as well as progression-free survival for patients with relapsed/refractory disease. Now, we have early-line trials – we have two trials with KarMMa-3 as well as CARTITUDE-4, that were done in a randomized Phase III fashion, where they were against standard of care treatment versus the CAR-T, and both of them significantly better PFS and overall response rate. And again, MRD undetectability compared to the standard of care options. So that tells us by prospective data that we should be doing our best therapies, first. And really they did beat out the standard of care options. So for that reason alone, just the efficacy, and, you know, toxicity was also, not worse than our standard of care, potentially better because the quality of life surveys that were done for both studies also show that quality of life actually improved drastically for the patients that got the CAR-T over any of the standard of care options. So, again, multiple reasons, just based on pure clinical trial data that says we should do CAR-T first, but then the logistics come in. And again, patients who are really relapsed/refractory, unfortunately, more of those patients don’t ever get to CAR-T. They either have manufacturing issues with manufacturing failure or out of spec cells, or their disease is just so bad that we can’t keep it controlled with bridging therapy because there’s no other options left for bridging therapy. And so then they end up with either, you know, subpar myeloma control going in where they end up with more risk toxicity like CRS, ICANS, HLH, IECHS, etc.. So going earlier, when you have a controlled setting and you can actually decrease that myeloma without having to give big doses of high dose chemo, decreases that infection risk, the cytopenias, and just more patients can actually get through the CAR-T process. So again, not just the data that’s out there, but even the logistics really show that if someone is going to get CAR-T, they really should do it earlier, to actually get the benefit of what CAR-T offers.
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