Cellular Therapies Had Especially Significant 2024, Including Earlier Treatment Lines

Since the first chimeric antigen receptor T cell (CAR-T) therapy was approved on Aug. 30, 2017, several similar cellular agents have followed, and 2024 was a particularly noteworthy year. Accomplishments included the first cell therapy for treating a solid tumor, the first new CAR-T since 2022 and two approvals of existing therapies in earlier lines of treatment.

On Feb. 16, 2024, the FDA gave accelerated approval to Iovance Biotherapeutics, Inc.’s Amtagvi (lifileucel) for the treatment of adults with unresectable or metastatic melanoma previously treated with a programmed death receptor-1 (PD-1) inhibitor and, if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor. The tumor infiltrating lymphocyte (TIL) therapy — which is created from patients’ unique T cells from their tumor as opposed to the T cells in a patient’s blood that the CAR-Ts use — is the first and only one-time individualized T cell therapy with FDA approval for a solid tumor cancer.

Last year, the FDA also approved the first new CAR-T since the February 2022 approval of Carvykti (ciltacabtagene autoleucel) from the Janssen Pharmaceutical Companies of Johnson & Johnson and Legend Biotech USA, Inc. On Nov. 8, 2024, the FDA approved Autolus Therapeutics plc’s Aucatzyl (obecabtagene autoleucel) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. While the therapy shares similar black-box warnings as the other CAR-Ts, the company said it is the first such agent approved without a Risk Evaluation Mitigation Strategy (REMS) program.

That agent joins six legacy CAR-Ts that have 17 approvals overall, with five of those happening in 2024. Three of those five went to Breyanzi (lisocabtagene maraleucel) from Bristol Myers Squibb unit Juno Therapeutics, Inc., which was first approved on Feb. 5, 2021. On March 14, 2024, the FDA granted it accelerated approval for adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic leukemia after at least two lines of therapy, making it the first CAR-T approved for that indication.

The next two approvals came within weeks of each other. On May 15, 2024, the agency gave Breyanzi accelerated approval for adults with relapsed or refractory follicular lymphoma after at least two lines of therapy. And then on May 30, 2024, the agent gained approval for relapsed or refractory mantle cell lymphoma after at least two lines of therapy.

“This FDA approval marks the fourth distinct subtype of non-Hodgkin lymphoma for which Breyanzi is approved, making it the CAR T cell therapy available to treat the broadest array of B-cell malignancies,” pointed out Bristol Myers Squibb after the third approval.

The other two CAR-T approvals, however, may have been the most significant among the legacy CAR-Ts. On April 4, 2024, the FDA approved Abecma (idecabtagene vicleucel) from Bristol Myers Squibb and 2seventy bio, Inc. for the treatment of adults with triple-class exposed relapsed or refractory multiple myeloma after at least two lines of therapy. The following day, the FDA approved Carvykti for the treatment of adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy.

Abecma was first approved on March 26, 2021, and Carvykti less than a year later on Feb. 28, 2022, both for the treatment of multiple myeloma after at least four prior therapies. People who have the disease often will relapse, so having it available in earlier-line settings is significant for patients for a couple of reasons. First, studies have shown that only a small percentage of patients will be able to actually receive a fifth line of treatment, so this expands the potential patient population. In addition, patients now can receive the one-time treatment in a more timely fashion without having to go through more continuous treatment.  

For the Managed Care Oncology Index: Q3 2024, from Aug. 19, 2024, to Sept. 16, 2024, Zitter Insights polled 36 commercial payers covering 121.1 million lives, 27 Medicare payers covering 47.3 million lives, 50 oncologists and 26 practice managers about their management and prescribing of multiple myeloma treatments.

AIS Health and Zitter Insights are both divisions of MMIT.

More than two-thirds of payers expressed moderate satisfaction with current treatment options, while half of oncologists said they were highly satisfied with them. Payers covering 60% of commercial lives and 77% of Medicare lives said there is moderate unmet need in the treatment of the disease, and 52% of oncologists agreed.

Still, 25% of payers and 32% of oncologists claimed that high unmet need exists. Among those respondents, all the payers and 77% of the oncologists said that the lack of effective drugs/unacceptable high number of nonresponders was the top reason for their perception of high unmet need.

Payers reported a varying level of aggressiveness in managing branded multiple myeloma therapies.

When asked about their management of the CAR-Ts as the agents are approved in earlier lines of treatment, 61% of payers said they will cover the therapies to label, but almost one-third said they would allow exceptions (see infographic).