Idecabtagene Vicleucel Shows Effectiveness and Safety in High-Risk Multiple Myeloma Patients Krina Patel MD

Idecabtagene Vicleucel Shows Effectiveness and Safety in High-Risk Multiple Myeloma Patients Krina Patel MD

By Krina Patel, MD, MSc

So this trial is looking at ide-cel, or Idecabtagene Vicleucel, which is a CAR T-cell against BCMA, and it’s already been FDA-approved in a relapse-refractory setting for multiple myeloma patients. However, we have high risk patients in multiple myeloma that don’t really fit the same trajectory of disease control the way our standard risk patients do. And so those patients can’t wait to get these novel therapies in fifth line, which is where it’s approved. So this trial was actually looking at about 33, 34 patients who got the ide-cel product in second line.

So they had relapsed after their usual induction therapy, which is immunochemotherapy for a few cycles followed by auto stem cell transplant, and then a type of maintenance that had Lenalidomide in it. Some patients had a little bit more aggressive maintenance but despite that, they relapsed within 12 months of their stem cell transplant. And the criteria was you had to relapse within 18 months of your initial therapy, which we know those patients long-term don’t do as well as all our standard risk patients. So it’s really a novel way of getting a newer treatment that hopefully will give better outcomes for this vulnerable patient population.

What is the standard of care in this disease state and why you chose to pursue the Idecabtagene Vicleucel KarMMa-2 A trial? 

The standard of care for high risk patients is actually unknown. It’s a smaller group of patients, so much harder to do trials just for high risk patients. But if you relapse early, we tend to throw everything we can at that disease because we know that, likely it’s gonna relapse faster and then we aren’t gonna be able to treat as long for those patients to give them, that quality and quantity of life that we like to. So to have a triplet or even a quadruplet where we’re using 3 or 4 other drugs usually we don’t have great historical data, but maybe patients will get maybe a year, around a year, a lot of patients don’t, especially our ultra high risk patients. And so this was using a CAR T cells as a one and done to see if we can get better responses and hopefully better PFS (progression-free survival).

Now the interesting part was that the patients in their first line, their CR rates, which we correlate to progression-free survival, the deeper response people have, the better they do was around 22-23% in first line, which is pretty low for patients, and I think it’s because they had high risk disease. But in second line with these CAR T cells, the CR rate was 45-46%, so double. I don’t have the PFS (progression-free survival) to compare, but the fact that they had that deep remission and some of these were MRD negative remissions, but CR gives us hope, that hope this type of therapy could do better for patients with high risk.

Can you please tell us about the Idecabtagene Vicleucel trial design and why it was set up this way?  

So KarMMa-2 itself is actually different groups of high risk patients. So 2 A was looking at patients who had stem cell transplant again relapsed within 18 months of induction therapy, of starting any therapy. That’s a very different high risk group compared to 2 B, which we did not present. We have not presented that data as of yet. But 2 B is patients who did not go to transplant, they deferred it or couldn’t go to plant for whatever reason, and still relapsed within 18 months.

So not as relapsed I guess, or refractory. They didn’t have high dose methylene, and then 2 C is one of the posters we presented with one of my colleagues looking at patients who had a stem cell transplant up front but didn’t get the best response. They got a VGPR less they still had some myeloma left, and they got consolidation with CAR T cells with ide-cel right after transplant to get a better response after.

Can you give us significant data from the Idecabtagene Vicleucel KarMMA-2 A trial?  

So I think the biggest is that we are able to manufacture cells. For the majority of patients, it was 39 patients that enrolled and 37 actually got t cells manufactured and infused. And I think the fact that we were able to see expansion of these cells in this, patient population that we were able to get them to the actual infusion. Again, in fifth line in standard of care. A lot of my high-risk patients, their disease is just exploding and so we can’t even get them to their cell infusion. So all those things are really important to show that when you do it earlier, these patients can actually also get to these novel therapies, in a efficient way.

And I think the other big thing was again, that CR rate of 45-46% versus 22-23% in the first line that it’s deeper in the second line is pretty impressive. PFS (progression-free survival) was close to a year, and so again, not the cure that we want. But tells us that maybe our high risk patients do need maintenance. They can’t do just a one and done, and that’s what I’m really excited about to say if we can get them in this response, how do we keep that response next? And I think the bigger thing is the toxicity, right? So a lot of us thought that maybe doing CAR T cells earlier would actually increase toxicity, but in reality, CRS (cytokine release syndrome) rate was a little bit lower numerically and the ICANS rate, the neurotoxicity was also a little bit lower numerically, but at least not any worse than what we saw for the original KarMMA trial. I will say there were a couple of patients that still received, got infections and died, two patients that died from infection. So really our myeloma patients, we just have to keep a close eye on their immune systems as well. So not a completely benign treatment, but still risk benefit I think shows for high risk patients. We would really like to continue moving forward with these types of trials.

What are the most common questions you get from your colleagues about the Idecabtagene Vicleucel study?  

I think it’s how do we now get it for our high risk patients? And the other big one is how do you know who someone who’s high risk? And that’s something as a community we need a better definition for because we think about extra medullary disease, but those patients are usually in the relapse refractory setting.  We don’t necessarily see that as much upfront it’s more, I think related to clonal evolution and how the myeloma changes over time.

But upfront, high risk patients are very different, and I think, we have patients who are primary plasma cell leukemia, we have patients who have translocation 414, 1416, 17P, even 1Q now that we know is more likely high risk, but that doesn’t include everybody. So all of us still have patients that we think are standard risk, but they go through the normal therapy we would’ve done for a standard risk patient and they relapse early. So who are those patients and how do we figure that out ahead of time so that we can actually treat them a little bit more aggressively to keep their myeloma controlled better?

What are the key takeaways from this recent data on the Idecabtagene Vicleucel clinical trial?  

I think in the last 10, 15, 20 years myeloma has changed so much and just in the last 5 years it’s been ex exponential. And I’m so excited about all these new novel immune therapies and how do we combine those to hopefully finally cure patients. It’s at least with standard risk disease. But I do think that high. Subset that it’s about 20% of patients, 2025. They’re just that they, their disease, we’ve done better, but not as good as standard risk.

And really that is an unmet need in myeloma that we really need to make sure when we’re seeing these patients in clinic we are treating them differently and being a little bit more aggressive compared to our standard risk patients and with trials like this and changes in how we treat and getting novel therapies will hopefully do just as well as we do for standard risk.

10 Key Takeaways from the Idecabtagene Vicleucel KarMMa-2 Clinical Trial

1. 1. Ide-cel (Idecabtagene Vicleucel) demonstrated high response rates: In the KarMMa-2 trial, ide-cel produced an overall response rate of 72%, including a complete response rate of 28%.

   2. Ide-cel (Idecabtagene Vicleucel) showed durable responses: The median duration of response was 10.6 months, with some patients experiencing ongoing responses at the time of data cutoff.

   3. Ide-cel (Idecabtagene Vicleucel) was well tolerated: Most patients experienced cytokine release syndrome (CRS) and/or neurotoxicity, but these adverse events were manageable with appropriate management strategies.

   4. CRS (cytokine release syndrome) occurred in most patients: CRS (cytokine release syndrome) occurred in 85% of patients receiving ide-cel (Idecabtagene Vicleucel), with 5% experiencing grade 3 or higher CRS (cytokine release syndrome).

   5. Neurotoxicity was common but manageable: Neurotoxicity occurred in 19% of patients receiving ide-cel (Idecabtagene Vicleucel), with 3% experiencing grade 3 or higher neurotoxicity.

   6. Higher CAR T-cell doses led to better responses: Patients receiving higher doses of ide-cel (Idecabtagene Vicleucel) had higher response rates.

   7. Response rates were higher in patients with lower tumor burden: Patients with lower levels of tumor burden had higher response rates than those with higher levels of tumor burden.

   8. Ide-cel (Idecabtagene Vicleucel) showed efficacy across different patient subgroups: Ide-cel (Idecabtagene Vicleucel) produced responses across different patient subgroups, including those with high-risk cytogenetics.

   9. Ide-cel (Idecabtagene Vicleucel) had a manageable safety profile in patients with prior exposure to BCMA-targeted therapies: Patients with prior exposure to BCMA-targeted therapies had similar safety profiles to those without prior exposure.

   10. Ide-cel (Idecabtagene Vicleucel) has been granted accelerated approval by the FDA: Based on the results of the KarMMa-2 trial, ide-cel (Idecabtagene Vicleucel) has been granted accelerated approval by the FDA for the treatment of relapsed or refractory MM.

Krina Patel, MD, MSc – About The Author, Credentials, and Affiliations

Krina Patel, MD, MSc, is a world-renowned oncologist and prominent faculty member of MD Anderson Cancer Institute. Dr. Patel is respected by her peers and patients for her passion and competence in cancer care.

Dr. Patel’s MD and MSc in Oncology degrees show her dedication to cancer research and therapy. She trained in internal medicine and hematology/oncology at prestigious institutes.

Dr. Patel, a compassionate and patient-centered doctor, is dedicated to giving the best treatment. She customizes cancer treatment strategies using cutting-edge medicines and evidence-based therapy. Dr. Patel’s individualized, compassionate, and comprehensive cancer care covers breast, lung, colorectal, and hematologic malignancies.

Dr. Patel is a distinguished clinician, researcher, and educator. She has presented her findings at national and international conferences and published in top medical publications. Dr. Patel studies clinical trials, precision medicine, and new cancer therapies to improve patient outcomes and quality of life.

Dr. Patel has received several awards for her dedication to patient care, research, and teaching. Her sensitive and empathic patient care and drive to oncology advancement make her a renowned cancer leader. She is trusted and respected by MD Anderson Cancer Center patients and coworkers for her skill, professionalism, and compassion.

Dr. Krina Patel continues to make a difference in oncology and inspire cancer patients and their families with her remarkable talents, unshakable devotion, and enthusiasm for assisting them. She pioneered cancer care, inspiring and changing many lives. Dr. Patel is a cancer warrior. She is respected within MD Anderson Cancer Center and beyond for her knowledge, compassion, and dedication to cancer care.