Usmani Projects a Future of CAR T in Community for Myeloma and Other Cancers

This is the second article of a 2-part series. See the first part here.

CASE SUMMARY

• A 60-year-old woman was diagnosed with Revised International Staging System (R-ISS) stage II/R2-ISS stage III IgGκ multiple myeloma​.
• Medical history: acute onset of renal insufficiency and hypercalcemia ​
• Cytogenetics: 1q21+ amplification; t(14:16); high risk​
• ECOG performance status: 0​
• Patient was considered transplant eligible.​
• She received daratumumab (Darzalex), bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone, followed by lenalidomide plus bortezomib maintenance.​
• Achieved ​very good partial response post-induction therapy.
• Patient underwent stem cell mobilization and 2 months later underwent autologous stem cell transplant (ASCT).
  • Achieved VGPR post-ASCT

Two Years Later

• The patient continued lenalidomide maintenance therapy​.
• On routine follow-up, she reported having mild fatigue but continued to work full-time​.
  • Bone marrow plasma cells, light chains, and M protein levels rising​
  • Kidney function worsening; estimated glomerular filtration rate: 28.7 mL/min/1.73 m²​
  • Now stage IV chronic kidney disease​
• Following second relapse, the patient was initiated on daratumumab, carfilzomib (Kyprolis), and dexamethasone with a best response of VGPR.

One Year Later

• After 2 prior lines of therapy​, the patient presented to her oncologist with complaints of increased fatigue and persistent bone pain in her lower back exacerbated by minimal movement​.
• She expressed interest in chimeric antigen receptor (CAR) T-cell therapy with her clinical team.​
• She also stated that she wants to travel out of the country for her daughter’s wedding in 3 months.
• The patient ultimately proceeded to CAR T-cell infusion.
• Patient demonstrated stringent complete response (CR) at day 30.

Saad Z. Usmani, MD, FACP, MBA

Myeloma Specialist & Cellular Therapist

Memorial Sloan Kettering Cancer Center

New York, NY

Targeted Oncology: What would the quality of life (QOL) be for this patient if she received ide-cel (idecabtagene vicleucel; Abecma)?

Saad Z. Usmani, MD, FACP, MBA: The QOL of patients after CAR T recovery is quite remarkable.1 They're not on any maintenance treatment and so, they have really good quality of life. They're just coming in once a month for their laboratory tests and to see every other month and they do fine. You can watch for the disease relapse based on symptoms or laboratory results.

What have the real-world results for ide-cel shown?

In the real world, there has been a CIBMTR study that was published on 600 or so patients who have received ide-cel and the patterns were very similar to what was observed in the clinical trials in terms of cytokine release syndrome, grading, and neurologic adverse events.2 Patients who get to a complete response or better, the anticipated median progression-free survival for those patients as well is very much in line with what's been [published in clinical trials]. Patients who have had prior BCMA treatments, such as bispecific antibodies or antibody-drug conjugates, still respond to ide-cel, and BCMA loss is not a common mechanism of [resistance] that we see in patients, so you can rechallenge patients with different BCMA-directed treatments. There's a difference in how much mileage you get out of that intervention. It's not the same as someone who is not BCMA-exposed, but you still get some bang for the buck.

Is CAR T-cell therapy a reasonable option for community centers?

For CAR T-cell therapy, we eventually want to get to a place where it's more commonly available, that even smaller centers will be able to deliver that product and have that efficacy. We're focused on myeloma right now, but…there are CAR T cells coming for lung cancer and breast cancer. All the good things start in hematology, and then get expanded to other malignancies. Once you get [options like] a relapsed non–small cell lung cancer CAR T cell, the community hospitals will develop mechanisms to manage those patients and build smaller programs.

I think the cost of therapy will also decline as these technologies become more readily available and even potentially have point-of-care treatment. I'm talking about the future; we started with hematology, with some lymphomas and myeloma, but I can tell you that more than half of the CAR T that we have on service at Memorial Sloan Kettering Cancer Center are the experimental solid tumor CAR T cells. That train is coming and so it's not going to be just at academic centers. There's no way possible, even with all the resources that big centers have, that you can manage that kind of capacity. We will never be able to have 5000-bed hospitals just focused on managing that kind of volume. And 80% of the cancer care happens in the community, so that's the only way to move forward, honestly.

_References:

_{1. Delforge M, Patel KK, Eliason L, et al. Effects of idecabtagene vicleucel (ide-cel) versus standard tegimens on health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 2–4 prior regimens: updated results from the phase 3 KarMMa-3 trial. Blood. 2023;142(1):96. doi:10.1182/blood-2023-179152}

_{2. Sidana S, Ahmed N, Akhtar OS, et al. Real world outcomes with idecabtagene vicleucel (Ide-Cel) CAR-T cell therapy for relapsed/refractory multiple myeloma. Blood. 2023;142(suppl 1):1027. doi:10.1182/blood-2023-181762}