Coordination Is Essential During and After Referral for CAR T in Myeloma
During a live event, Konstantinos Sdrimas, MD, and community oncologists discussed patient concerns over CAR T-cell therapy toxicity and how to coordinate with CAR T providers.
Konstantinos Sdrimas, MD
In more rural areas with less access to academic cancer centers, the selection of chimeric antigen receptor (CAR) T-cell for relapsed/refractory multiple myeloma poses additional challenges and makes cooperation between community and academic oncologists vital. In a recent virtual Case-Based Roundtable meeting that brought together oncologists from across the state of West Virginia, Konstantinos Sdrimas, MD, assistant professor of medical oncology at the West Virginia University (WVU) Cancer Institute in Morgantown, heard from other oncologists about what concerns patients have with the toxicities of CAR T-cell therapy and how confident they are referring patients and resuming care for patients who return after receiving this treatment.
This article is part 2 of a 2-part series from a Case-Based Roundtable event.
DISCUSSION QUESTIONS
- What factors do you prioritize when selecting bridging therapy for your patients?
- To further optimize the timing and overall care of patients, what strategies would you advise to both academic institutions and community practices?
Konstantinos Sdrimas, MD: In preparation for patients to receive CAR T, what factors do you prioritize when selecting bridging therapy for the patients?
Donald Fleming, MD: I think it's something we probably should discuss with the [physician] who is doing the CAR T. I always like to know if there's any [therapy] that's going to burn any bridges or not. Things like steroids would be something you wouldn't want to give too much of before you referred the patient. I don't know about any other BCMA [B-cell maturation antigen]–targeted therapies. Usually, we wouldn't be using bispecifics. In the past we had belantamab mafodotin [Blenrep]. I don't know if there would be some issues in the future about BCMA loss if you use that before CAR T. In the future, that might be an issue.
Sdrimas: That's a very good point, because it seems that the response rates are statistically significantly lower after previous BCMA-targeted treatment exposure.1 But otherwise, I agree with you that it's very important to refer the patient so the process starts, and then to discuss with the CAR T provider about what's going to be a good bridging regimen to get the patient to the CAR T. That question is more relevant to when it comes to using BiTEs [bispecific T-cell engagers] or other BCMA-directed treatment before CAR T and the impact that may have on the subsequent CAR T response. To further optimize the timing and overall care of patients, what strategy would you advise to both academic institutions and community practices?
Ihtishaam Qazi, MD: Good communication between the transplant team and the local oncologist. [WVU] does a good job of communicating those things.
Sdrimas: I think WVU has a good system for communicating with providers in the state. The fact that I know most of you means a lot, and we can very easily communicate when it comes to these things. I think that we do a good job.
DISCUSSION QUESTION
- Based on the CARTITUDE-4 trial (NCT04181827) results:
- How do the recent efficacy and safety data impact your treatment selection for ciltacabtagene maraleucel (cilta-cel; Carvykti) in patients with multiple myeloma at first relapse?
Fleming: Any time a patient is facing something like this, you have to have them weigh heavily on the decision, because it's going to involve going to another [cancer center]. I think some of the unknowns are the most frightening to patients, things like ICANS [immune effector cell–associated neurotoxicity syndrome. CRS [cytokine release syndrome] is pretty much something that can be controlled, but we're hearing about a lot of delayed neurologic [issues], so a lot of patients get concerned about the unknowns more than anything else. It's a one-shot deal, which is very attractive to the patient because they're not used to just getting a treatment in myeloma and you're done. I think that's a great thing, but there are some unknowns that they hear about in the news, like somebody getting parkinsonism.
Sdrimas: One of the beauties of CAR T especially in early lines of treatment is the fact that it is the first time that you can offer a person with myeloma time without treatment. That's a very big thing for a lot of the patients. I agree with you that a lot of the toxicities, especially some of the some of the neurotoxicity, have gotten a lot of attention, especially some of the toxicities that came out of the CARTITUDE-1 trial [NCT03548207] that reported a high percentage of adverse events [AEs], including secondary malignancies that got a lot of publicity, but...even the CRS, which sounds very scary, most of them are grade 1 and 2, it's very easy to manage them, and they resolve very quickly.
Qazi: When immunotherapy came out, there was a lot of worry about the AEs, and then we got used to it, and we were able to recognize AEs early on. Are there any real-world data? It's been around long enough now in high-volume centers. Are they seeing that the rates of ICANS and CRS have gone down compared with the original trials because now we're much more facile at recognizing these symptoms?
Sdrimas: The CRS and ICANS toxicity in the real world is very similar to the rates reported in the trial. In our experience here at WVU, initially we had much more ICANS than what was reported, but now after doing idecabtagene vicleucel [ide-cel; Abecma] for several years and cilta-cel starting in October [2024], now our numbers match what is reported. I don't think that the incidence changes, but we're getting better at recognizing it and starting treatment.
Mohammad Ahsan Alamgir, MD: Do newer generation CAR Ts have a better AE profile? When [CAR T-cell therapy trials] started up 10 to 11 years ago, there were so many fatalities that they had to stop the trials and then reevaluate before they started. Are new CAR Ts better, or are we better at recognizing it, or are we better at treating the AEs?
Sdrimas: There are newer formulations of CAR T under development now that have a feedback mechanism that prevents excessive activation of them. There are a lot of things in the pipeline, but for the commercially available CAR Ts, what has helped is us being more aware of the toxicities and having more experience how to handle it, more than seeing less of it. But I believe that what's coming in the future is CAR T-cell therapies that have a better toxicity profile because they're either modified to mitigate the toxicity, or the binding of the antigen in the CAR T is very different. But none of that is something that has been approved or is available to us at the moment.
[Early toxicities] are more of a question for us [physicians who administer] the CAR T-cell therapy. But a lot of these patients will be released from us within a short period of time. Cytopenias are something that a lot of people in the community see and deal with, with our help. I don't expect people to see or manage ICANS or CRS in the community. But cytopenias are something that a lot of you deal with as well.
DISCUSSION QUESTIONS
- Following CAR T, how do you decide when to transition the patients back to the community?
- What clinical scenarios would require patients to stay longer at an academic center?
Jacob Fuqua, MD: Usually, they try to send them back to the community within the first month, at 30 days, but still with a comanagement system. They have them come back. I think we're doing vaccines now for all of our [patients receiving] CAR T, like they do with autologous transplants, or at least they're working on that program. The IVIG [intravenous immunoglobulin] has been a bigger issue. But I think there are a couple patients who get IVIG locally, and then we help when they're done. [They would stay longer at the] academic center if they had bad CRS or ICANS or got an infection while they’re still here.
Sdrimas: Initially, when we started doing them, we monitored the person for 1 month, or 28 days here in Morgantown, even patients who didn't have any significant toxicity. Now we have significantly shortened that interval. With patients who do well and are out of the CRS and the ICANS window, we get them back to the community much faster, and we'll always try to not lose contact with these patients. We try to see them together with a local oncologist to manage some of the late AEs, but I think the trend is to try to get people back to their local oncologist as soon as possible.
DISCLOSURES: There were no known relevant disclosures.
