Second CAR T Cell Immunotherapy Approved for Patients with Lymphoma

On May 1, 2018, the FDA approved a second CAR T cell immunotherapy—Novartis's Kymriah® (tisagenlecleucel)—for patients with relapsed or refractory large B cell lymphoma, a type of blood cancer.

Like the first lymphoma-approved CAR T cell immunotherapy, Kyrmiah® also extracts a patient’s existing T cells and then engineers them to express a chimeric antigen receptor (CAR) that targets the CD19 receptor. This receptor provides an important target because it’s found almost universally on B cells, including those that become cancerous in lymphoma or leukemia. Kymriah® is already FDA-approved for children and young adults with relapsed or refractory leukemia.

“[The] FDA approval of Kymriah provides another opportunity for Novartis to build on its leadership in CAR-T development, delivering a potentially transformative therapy with durable and sustained response rates and a well-characterized safety profile to help patients in dire need of new treatment options,” said Novartis’ chief executive officer, Liz Barrett.

Kymriah’s recent approval in lymphoma covers patients who have received at least two prior systemic treatments—but not those with primary central nervous system lymphoma—and was based on results from the phase II JULIET clinical trial, which is the largest CAR T cell lymphoma trial in the world, involving patients treated at centers located across ten countries and four continents.

In the JULIET trial, doctors witnessed responses in half of the 106 patients who received a single dose of this “living drug” after chemotherapy. Of the patients that responded, 64% had complete tumor regression, and the patients who experienced complete responses had more durable responses, suggesting this approach has the potential to provide long-term benefits for patients.

It’s important to note that lymphoma patients treated with Kymriah® had lower response rates compared to Kymriah-treated leukemia patients in prior trials.

While unfortunate, this wasn’t unexpected, and reflects the challenges involved with translating this novel cell-based immunotherapy approach from purely “liquid” cancers like leukemia to tumors that grow in more “solid” environments (i.e., tumors that reside within tissues that provide a physical architecture for cancer cells). Compared to leukemia, in which the CAR T cells are directly exposed to the cancer cells in the blood, there are more hurdles the CAR T cells must clear if they are to infiltrate into and eliminate solid tumors.

Fortunately, the promising potential of CAR T cells has motivated numerous efforts to crack the code of solid tumors and figure out how to effectively apply these immunotherapies to benefit more patient populations.