The U.S. Food and Drug Administration (FDA) approved CAR T-cell therapies for various types of blood cancer – only after two rounds of therapy have not worked, in most cases.
Expanding the approval – to after one round of unsuccessful therapy – could offer hope to many more cancer patients.
A new study from the publication “Transplantation and Cellular Therapy” measures the impact of expanded access to this cancer cell and gene therapy.
According to the article, only a small percentage of patients ever reach eligibility for CAR T-cell therapy. Their cancer must not respond to at least two rounds of standard of care therapy or relapse at least twice after successful therapy.
Depending on the type of cancer, the first line of standard of care can be systemic chemotherapy or immunotherapy. The second line, for many blood cancers, is a stem-cell transplant in addition to more chemotherapy.
The American Journal of Managed Care publication reported a second-line approval of YESCARTA (axicabtagene ciloleucel, or axi-cel) for large B-cell lymphoma could come by April 1, 2022. The website CURE reported the FDA will decide on BREYANZI’s (lisocabtagene maraleucel, or liso-cel) application for large B-cell lymphoma by June 24, 2022. Either approval could happen before these target dates.
These expected FDA decisions could provide access to CAR T-cell therapy for an estimated 11,000 additional blood cancer patients just in the United States.
CAR T-cell therapies approved for cancer
Alliance was instrumental in funding the research behind the first approvals of CAR T-cell therapies. The FDA approved the novel cell and gene therapy, tisagenlecleucel, for pediatric cases of acute lymphoblastic leukemia and cases of non-Hodgkin lymphoma after at least two rounds of therapy didn’t work. Tisagenlecleucel is known as the brand name, KYMRIAH®.
Since that first approval, the FDA has approved five other CAR T-cell therapies for various types of blood cancer.
For all but one of the approved products, patients become eligible for CAR T therapy after two lines of other therapy have not worked:
- YESCARTA® for non-Hodgkin lymphoma, which includes large B-cell lymphoma
- TECARTUS® (brexucabtagene autoleucel) for mantle cell lymphoma and acute lymphoblastic leukemia
- BREYANZI® (lisocabtagene maraleucel) for types of non-Hodgkin lymphoma, including large B-cell lymphoma
- ABECMA® (idecabtagene vicleucel) for multiple myeloma after four lines of therapy
Advocates of cell and gene therapy hope the FDA will expand eligibility for these CAR T-cell therapies to second-line treatment for large B-cell lymphoma. This action would make the promising treatment available in cases when one round of chemotherapy is unsuccessful, which could have a significant impact for many patients.
Limited patient access to CAR T-cell therapy
Researchers from the American Society for Transplantation and Cellular Therapy analyzed 125 cases of relapsed or treatment-resistant large B-cell lymphoma, a type of non-Hodgkin lymphoma. KYMRIAH, YESCARTA, and BREYANZI are approved for this type of blood cancer.
Of the 125 cases, 82% had disease growth within a year of starting chemoimmunotherapy:
- Approximately half of those relapsed patients were approved for a stem-cell transplant
- Around half of the approved stem-cell patients received a transplant
- One-third of transplant patients had tumor growth after the transplant
This left 7% of the initial 125 who qualified for CAR T-cell therapy, if they survived long enough to receive the innovative treatment.
By comparison, CAR T-cell therapy in the second line seemed more advantageous to patients. Researchers reported that around 65% of cases with disease growth after first-line chemoimmunotherapy qualified for second-line use of the CAR T-cell therapy YESCARTA. This equals around 66 of the original 125 patients, versus approximately 10 patients for those treated after not benefiting from two rounds of therapy.
“Whereas the current standard of care results in poor outcomes for most patients with large B-cell lymphoma, the use of CAR-T cell therapy in second line could substantially increase the proportion of patients able to receive curative-intent treatment at first progression,” the researchers wrote.
Clinical trial success for CAR T-cell therapies in second line
Recent studies show CAR T-cell therapy outperforms stem-cell transplant plus chemotherapy for some patients. Two phase 3 clinical trials – one featuring YESCARTA and the other featuring BREYANZI – provide hope that the FDA may expand approvals for types of lymphoma:
- YESCARTA quadrupled event-free survival – survival before the patient experiences a symptom or adverse event from treatment – compared to standard of care.
- YESCARTA’s two-year survival rate was 61%, up from standard of care’s 52% rate.
- BREYANZI’s event-free survival was nearly five times that of stem-cell transplant with chemotherapy.
- BREYANZI’s progression-free survival was 14.8 months, significantly better than the current second-line regimen (5.7 months).
The results are clear: CAR T-cell therapy as a second option of treatment improves outcomes for many patients.
Should CAR T cells be approved for first-line therapy?
Approving CAR T-cell therapy as an earlier option would be a major shift away from relying on chemotherapy, especially early in the treatment process. Patients have to be treated using the standard of care chemotherapy and/or radiation before they can become eligible for cell and gene therapies. The challenging impact of chemo and radiation on patients is well known.
Based on clinical research, there is certainly patient benefit to making CAR T-cell therapy available in the second line of treatment. There could be even more benefit to making this option available right away, without any requirement for not using standard of care or another therapy.
This possibility is on the minds of scientists and biomedical leaders – and may soon be at the FDA’s desk. The ZUMA-12 clinical trial, a single-arm phase 2 study, used YESCARTA as a first-line therapy for large B-cell lymphoma. The results were encouraging:
- 89% overall response rate, meaning tumors at least stopped growing and possibly shrank
- 78% complete response rate, meaning there were no signs of tumors on follow-up scans
- 91% one-year survival rate
Alliance for Cancer Gene Therapy will continue reporting about the progress of cancer cell and gene therapies, including news of FDA approvals. This progress reduces the reliance on chemotherapy and opens more options for patients with chemo-resistant blood cancers or even solid tumors.
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- Real-world eligibility for second-line CAR-T cell therapy in large B-cell lymphoma: a population-based analysis. Transplantation and Cellular Therapy. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/35123117/. Accessed: 02/14/2022.
- With Approval for Axi-cel in Second-line on the Horizon, CAR T-Cell Therapy Poised to Enter New Phase. American Journal of Managed Care. Retrieved from: https://www.ajmc.com/view/with-approval-for-axi-cel-in-second-line-on-the-horizon-car-t-cell-therapy-poised-to-enter-new-phase. Accessed: 02/16/2022.
- FDA Agrees to Review CAR-T Cell Therapy for Second-Line Treatment of Large B-Cell Lymphoma. CURE. Retrieved from: https://www.curetoday.com/view/fda-agrees-to-review-car-t-cell-therapy-for-second-line-treatment-of-large-b-cell-lymphoma. Accessed: 02/18/2022.