Episode 150: Myeloma Series, Pt. 10 - Role of CAR T for relapsed/refractory multiple myeloma (2026)
In this week’s episode, we take a practical dive into the relapsed/refractory myeloma space, with a focus on the role of CAR T therapy for relapsed/refractory. In our next episode, we will continue on with a discussion on bispecific agents! This is a conversation that is so important in the current treatment landscape and one that you don’t want to miss.
This episode is sponsored by The Lymphoma, Leukemia and Myeloma Congress! To learn more and register for the meeting, click here! Be sure to use our SPECIAL TFOC code TFOC40 to save 40% off registration.
What are treatment options for patients who progress through first line therapy?
The general rule is to treat patients with therapies they had not previously been exposed to
Different proteosome inhibitors: Since bortezomib is often used in the front-line, can consider carfilzomib, which has great outcomes based on CANDOR trial
Immunomodulatory agent: Since lenalidomide is often used, consider pomalidomide
If they have not been exposed to anti-CD38 antibody, consider adding
Great Mayo Clinic document: https://www.msmart.org/mm-treatment-guidelines
In the current treatment landscape, many patients are also being referred for cellular therapy options including chimeric antigen receptor T-cells (CAR T) and T-cell engager antibodies (often called bispecific antibodies)
Will be important to still keep carfilizomib-based regimens in mind as “bridging” therapy
What are the fundamentals of CAR T as it relates to myeloma treatment?
Be sure to check out episode 075 where we discussed CAR T (including a great video!) highlighting how they work
CAR T is a form of immunotherapy where a patient’s own T-cells are obtained via apheresis and are then sent to a manufacturer where they are modified ex vivo to have a “chimeric receptor” on their surface
What is “chimeric” about them? They have three components that are normally separate but have been fused into one receptor: an extracellular domain, a T-cell activation domain, and a co-stimulatory domain.
The extracellular domain targets the myeloma cells and in the current treatment landscape, the target antigen is B-cell maturation antigen (BCMA)
BCMA is found widely on plasma cells and other B-cell lineage cells.
As the name implies, the T-cell activation domain is the portion that allows the T-cell to become activated and trigger an immune response once it binds to BCMA. This is typically done with CD3-zeta.
The co-stimulatory domain helps to keep the activation signaling, and this is generally done with 4-1BB.
What are the current (at the time of our recording) available CAR T options for patients?
Idecabtagene vicleucel (“Ide-cel” for short, Brand name: Abecma)
Ciltacabtagene autoleucel (“Cilta-cel” for short, Brand name: Carvykti).
Keep in mind that none of the products that we are discussing today have been directly compared head-to-head in a randomized trial, so any discussion of similarities and differences must be viewed in that context.
What is the key trials leading to the approval of these agents?
Ide-cel: KarMMa-3 (NEJM, Feb 2021)
KarMMa-3
All patients had progressed through at least 2-4 prior lines of therapy (and were required to have previously received daratumumab)
Patients were randomized to receive ide-cel versus standard of care with typical combination regimens used for relapsed disease
Standard of care consisted of one of five approved regimens: DPd, DVd, ixazomib-RD, Kd, EPd
The median PFS with ide-cel was 13.3 months, compared to 4.4 months in the standard of care arm
The median OS with ide-cel was 41.4 months, compared to 37.9 months in the standard of care arm
This was not statistically different - however crossover was allowed in this trial, and 56% of patients who were initially assigned to standard of care eventually crossed over and received ide-cel when they progressed
Cilta-cel: CARTITUDE-4 trial (NEJM 2023; update in Lancet 2026)
CARTITIUDE-4
All patients had progressed through 1-3 prior lines of therapy
Prior daratumumab exposure was NOT required, and only about a quarter of patients had been on daratumumab before.
Patients were randomized to receive cilta-cel versus standard of care with combination regimens used for relapsed disease
Standard of care options: PVd or DPd
At the time of the initial publication, the median PFS and OS had not yet been reached with cilta-cel.
However, an updated analysis of CARTITUDE-4 was just published in February 2026.
PFS at 30 months was 59% with cilta-cel versus 26% with standard of care.
OS at 30 months was 76% with cilta-cel versus 64% with standard of care.
Note: Unlike with the KarMMa trial, patients in CARTITUDE-4 who progressed on the standard of care arm were NOT allowed to cross over to receive cilta-cel.
What patients should we consider referring for CAR T?
Younger patients
Patients with rapid relapse of disease
Keep in mind that there is no head to head comparisons between Cilta-cel and Ida-cel, but with very impressive data in CARTITUDE-4, many will reach for Cilta-cel
What are the major differences in side effect profiles between ida-cel and cilta-cel?
Shared side effects:
Cytokine release syndrome (CRS)
Immune effector cell associated neurotoxicity syndrome (ICANS)
See episode 075 for more information on these
Cytopenias, infections, and a delayed HLH-like syndrome that we call IEC-HS.
A key difference: Cilta-cel was also associated with what we call “non-ICANS neurotoxicity”
These are delayed neurologic symptoms that can include things like cranial nerve palsies, atypical Guillain-Barre syndrome, and most importantly, Parkinsonism.
Parkinsonism symptoms occurred in about 6% of patients in the initial CARTITUDE-1 trial and about 1% of patients in the CARTITUDE-4 trial.
How do you choose one option over the other?
Remember that there are no head-to-head comparisons and fundamentally there are differences in the ways the trials were designed, including:
Prior daratumumab exposure
Cross-over option
The prevailing opinion in the myeloma community is that cilta-cel seems to be more likely to keep patients in remission for a longer period of time.
Part of this comes from data from the single-arm CARTITUDE-1 study. These patients had all progressed through at least 3 lines of therapy, but even though they had advanced disease we saw a median overall survival of 60 months on long-term follow up.
This is also backed by real-world analysis which show an association with longer PFS and OS in cilta-cel compared to ide-cel (albeit with higher rates of infection, severe CRS, and delayed neurotoxicity)
Need to always consider the side effect profiles in the context of your patient
Helpful review article on CAR T (and bispecific agents): https://ashpublications.org/hematology/article-abstract/2025/1/324/556925/CAR-T-cell-therapy-and-bispecific-antibodies-in?redirectedFrom=fulltext
What are the logistics of CAR T?
Insurance approval
After CAR-T is approved, the first real step is the T-cell collection, which involves collecting a patient’s T-cells via apheresis.
Keep in mind that before we start collection, we generally need to hold any myeloma treatments for at least 7-14 days to ensure good quantity and quality of collected T-cells.
Once the T cells are collected, they’re shipped to the manufacturer where they’re re-engineered with the recombinant CAR-T receptor.
Manufacturing can take anywhere from 4-6 weeks on average, and once manufacturing is complete the cells are shipped back to the clinic.
During this time, patients will frequently receive some sort of bridging therapy.
A few days before patients receive their CAR-T cells, patients receive lymphodepleting chemotherapy
Finally, the patient receives their CAR-T cells.
All of this means that the patient’s myeloma needs to be stable enough to allow time for this to all happen - if a patient’s myeloma is rapidly progressing, they may not be able to wait long enough to go through all of the steps that it takes to get CAR-T treatment.
This episode is sponsored by The Lymphoma, Leukemia and Myeloma Congress! To learn more and register for the meeting, click here! Be sure to use our SPECIAL TFOC code TFOC40 to save 40% off registration.
The crew behind the magic:
Show outline: Vivek Patel, Sean Taasan
Production and hosts: Sean Taasan, Vivek Patel, Ronak Mistry
Editing: Resonate Recordings
Shownotes: Ronak Mistry
Graphics, social media management: Ronak Mistry
