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FAQ: CAR T-Cell Therapy
Frequently Asked Questions About CAR T-Cell Therapy

Released: March 24, 2020

Expiration: March 23, 2021

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This commentary features a selection of questions asked by participants during an ASH 2019 satellite symposium focused on current best practices and emerging directions in CAR T-cell therapy, with responses provided by members of the program faculty.

As of March 2020, the CD19-targeted CAR T-cell therapies axicabtagene ciloleucel and tisagenlecleucel are both approved for use in the United States. Tisagenlecleucel is approved for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse. Tisagenlecleucel is also approved for adults with relapsed/refractory (R/R) large B-cell lymphoma after ≥ 2 lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from follicular lymphoma, and high-grade B-cell lymphoma. Axicabtagene ciloleucel is also approved for adults with R/R large B-cell lymphoma after ≥ 2 lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from follicular lymphoma, primary mediastinal large B-cell lymphoma, and high-grade B-cell lymphoma.

Timing of CAR T-Cell Therapy in Acute Lymphoblastic Leukemia

Does response rate vary if CD19-targeted CAR T-cell therapy is administered earlier or later in the treatment course?

The response rate is generally similar when CD19-targeted CAR T-cell therapy is administered earlier or later in the treatment course: approximately 70% to 80% in most studies. There are differences, however, in duration of remission and relapse rate after CAR T-cell therapy depending on when the treatment is administered and what the baseline disease burden is.

Should a patient with refractory disease and low disease burden receive an allogeneic stem cell transplant instead of CAR T-cell therapy, if possible?

That is an option. Transplantation does not cure all patients and there are toxicities associated with this procedure; transplant-related mortality remains between 15% and 20%. Although CAR T-cell therapy can be associated with significant toxicity, mortality with this treatment is significantly lower than that observed with transplantation. Although we await data from studies that compare CAR T-cell therapies with standards of care, including transplantation, it is the hope that earlier CAR T-cell therapy might improve outcomes for patients with refractory disease.

What treatments do patients receive after CAR T-cell therapy?

After CAR T-cell therapy, for patients who have achieved remission, there is generally no immediate maintenance or consolidation therapy, but for some, bone marrow transplantation may be a consideration. Once patients have received a single infusion of CAR T-cells, they are monitored closely for recurrence of disease with serial bone marrow biopsy and also observed for B cell aplasia; if relapse occurs, they receive standard salvage therapy.

CAR T-Cell Therapy for Lymphoma

Should patients receive maintenance treatment following CAR T-cell therapy?

As with acute lymphoblastic leukemia, current knowledge of treatment with CAR T-cell therapy is based on data from studies of a single infusion of the CAR T-cells, without maintenance therapy. In general, most people who fail CAR T-cell therapy do so within 3 months, even when there is CAR T-cell expansion, and there are ongoing studies examining the role of additional therapies for these patients. Once a patient maintains remission for 6 months, most responses appear durable, and no maintenance therapy is indicated.

Managing CAR T-Cell–Associated Toxicities

Does toxicity correlate with response to CAR T-cell therapy?

There are interesting data now emerging that suggest that severe toxicity may actually be detrimental to duration of response and overall survival in patients treated with CAR T-cell therapy, so there may be a middle ground where a certain amount of T cell expansion and cytokine-release syndrome and neurotoxicity might indicate better response, but extremes may be detrimental. However, this needs to be tested in a clinical trial setting.

Do you recommend NSAIDs following CAR T-cell therapy?

Any drugs that may injure the kidneys or lead to platelet dysfunction (as NSAIDs can) should be used with caution following CAR T-cell therapy.


Investigational Approaches to Treating Multiple Myeloma With CAR T-Cell Therapy

How do you explain the dose response observed with anti–B-cell maturation antigen (BCMA) CAR T-cell therapy for myeloma?

A dose response was observed with anti-BCMA CAR T-cell therapy for myeloma in multiple phase I studies, including a trial of idecabtagene vicleucel (formerly bb2121). At present, it is unclear why this should be. The effect may be CAR and disease specific; it is possible that by changing a CAR, the clinical outcome may in turn be changed.

How do you sequence CAR T-cell therapy with bispecific antibodies?

This is currently an unanswered question. In myeloma, treatment with bispecific antibodies is currently an experimental approach, as is CAR T-cell therapy, so any decisions would be based on clinical trial inclusion and exclusion criteria. Selected studies of agents further along in clinical trial development for patients with R/R multiple myeloma include the following:

  • Phase III trial of idecabtagene vicleucel (formerly bb2121; CAR T-cell therapy) vs standard triplet regimens (KarMMa-3/NCT03651128)
  • Phase I/II trial of AMG 420 (bispecific antibody; NCT03836053)
  • Phase I/II trial of REGN5458 (bispecific antibody; NCT03761108)

Future Directions

Are there any studies that compare CAR T-cell therapies with standard of care?

Currently, there are no data from studies comparing CAR T-cell therapy with standard care; however, there are currently several ongoing randomized phase III trials comparing CAR T-cell therapies with standard treatment approaches.

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