Dive Brief:

• The makers of CAR-T cell therapies will need to warn about the risk of new blood cancer, the Food and Drug Administration said, following a review of reports involving so-called T cell malignancies following their use.
• In Jan. 19 letters to the manufacturers of six CAR-T therapies, the FDA said the prescribing information will need to include boxed warnings, the strongest type. In communication with industry executives, FDA officials have said they believe the benefits of these treatments, which are approved for types of lymphoma, leukemia and multiple myeloma, outweigh their risks.
• Since the FDA’s review began in late November, academic researchers have been probing the issue, too. One cell therapy advocacy group noted how the rate of 20 cases of T cell malignancies in roughly 34,000 CAR-T treated patients “is notably lower than that reported for more conventional alternative treatments.” The organization called for more studies to determine if some patients are at higher risk than others.

Dive Insight:

The CAR-T therapies — Abecma and Breyanzi from Bristol Myers Squibb, Carvykti from Johnson & Johnson and Legend Biotech, Kymriah from Novartis, and Tecartus and Yescarta from Gilead — can drive deep and durable responses in patients with lymphoma, leukemia and multiple myeloma who have progressed following numerous other treatments.

These therapies are made from patients’ own T cells, which are genetically engineered with a “chimeric antigen receptor,” or CAR, that’s aimed at certain protein flags found on malignant cells. Once reinfused, the cells home in and destroy cancers that express that flag. The approved ones target proteins called CD19 or BCMA.

The current labeling already warns of secondary malignancies. However, the FDA in November announced it was investigating malignancies “including chimeric antigen receptor CAR-positive lymphoma.” Those reports came from clinical trials and postmarketing adverse events data sources.

In a presentation at the Alliance for Regenerative Medicine meeting on Jan. 8, Peter Marks, director of FDA’s Center for Biologics Evaluation and Research, told CAR-T makers that they need to monitor clinical trial enrollees and patients receiving CAR-T post-approval for the rest of their lives to identify new malignancies, and test for the CAR gene when they do happen.

A day after Marks’ presentation, the International Society for Cell and Gene Therapy published an expert consensus statement on CAR-T risks, calling for continued evaluation but urging continued access.

The regulatory evaluation appears to have created new speed bumps as CAR-T makers seek to gain approval or expand use, however. In a regulatory filing Tuesday, Legend Biotech disclosed the FDA and European Medicines Agency both intend to call in expert advisers to review its application for Carvykti use in a second-line multiple myeloma setting. It is currently only approved for use only after patients progress on four lines of therapy.

The FDA is also convening an advisory panel to consider earlier use of Bristol Myers’ Abecma.