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“cytokine storm,” which essentially is the immune system going into overdrive and causing system-wide inflammation. The condition can be quite serious, and everyone involved in the new CAR-T field is working on ways to alleviate it.
Of the 20 patients in Juno’s ALL study, nine developed cytokine release syndrome, or CRS. (They all began treatment with an acute presence of disease, not just residual effects from previous treatments.) Researchers measured the cytokine levels, in particular the protein interluekin-6 (IL-6), and are developing a strategy to “reduce the severity of CRS and improve safety” of the therapy. In all, researchers wrote in the abstract, both the relapse rate and the development of safety protocols to alleviate side effects “strongly support” the continued use of the therapy, although they underscore that it’s still early days: “These findings will need to be evaluated systematically and confirmed in a larger phase 2 trial.”
Novartis (NYSE: NVS), with a program called CTL019 licensed from the University of Pennsylvania, made big news at last year’s ASH in CAR-T right around the time Juno came out of stealth mode. This year, the Penn researchers are reporting follow-up data from a study of 30 children with acute lymphoblastic leukemia that didn’t respond to chemotherapy or stem-cell transplant. At first, the treatment provoked 27 complete remissions, but that number is now down to 16 for various reasons that are detailed in the abstract. As with the other CAR-T programs, the cytokine side effects are important, and the researchers write that treatment for CRS was required in 37 percent of patients “and was rapidly reversed in all cases with the IL-6 receptor antagonist tocilizumab, together with corticosteroids in 5 patients.”
Novartis, the only Big Pharma so far to invest heavily in a cell-based cancer immunology program, has moved CTL019 into Phase 2 trials, the abstract said.
In Los Angeles, Kite Pharma (NASDAQ: KITE) is working on CAR-T cell therapy that, like the Juno and Novartis programs described above, attacks tumors by honing in on a surface protein called CD19. (CD19 is found all over the surface of B cells, which, once gone awry, drive several blood-borne malignancies.) The University of California, Los Angeles spinout is working with the National Institutes of Health, and NIH researchers will present an update.
The abstract says 22 of 27 patients with B-cell lymphoma that hadn’t responded to chemotherapy showed either complete or partial remission, and 10 of them remain in complete remission over various lengths of time. The researchers were also interested in reducing the treatment’s side effects, so they tracked 9 patients who were given low doses of chemotherapy before CAR-T. (So far, CAR-T requires some amount of chemotherapy as a preparation.)
Compared to previous research in which anti-CD19 CAR-T was preceded by high-dose chemotherapy, the researchers said in the abstract, “toxicity was reduced when CAR-T cells were infused after low-dose chemotherapy. None of the 9 patients treated with low-dose chemotherapy and CAR-T cells required vasopressor drugs or mechanical ventilation, although some patients did have short-term neurological toxicity.”
In other words, this particular kind of cancer immunotherapy, from research groups related to Juno, Novartis, and Kite, is moving ahead into bigger trials and more patients. The spectacular early results of the treatments aren’t sustainable over time, it seems, and there are safety concerns, but so far nothing has forced anyone to slam on the brakes.