Novartis’ CAR-T cell therapy Kymriah (tisagenlecleucel) can now be prescribed to adult patients with relapsed/refractory follicular lymphoma after treatment with two or more lines of systemic therapy. Photo courtesy of Novartis: A cancer patient’s frozen T-Cells arrive at a Novartis facility to be reengineered.
Last week, Novartis announced that their CAR-T cell therapy Kymriah® (tisagenlecleucel) has been approved for a new indication under the US Food and Drug Administration’s (FDA) Accelerated Approval Program. Kymriah can now be prescribed for adult patients with relapsed/refractory (R/R) follicular lymphoma following treatment with two or more lines of systemic therapy. This is the third indication Kymriah has received since it was first approved in 2017. Earlier in May, Kymriah was also approved by the European Commission for relapsed/refractory follicular lymphoma patients in the European Union.
Treatment Options for Follicular Lymphoma
Follicular lymphoma, or FL, is a rare cancer that is a subtype of Non-Hodgkin lymphoma. Clinical signs include inflamed lymph nodes and enlargement of the spleen. Following initial treatment, many patients experience cycles of relapse and remission. As the disease becomes more resistant to therapy, it is more difficult to treat.
Treatments for FL include standard first-line cancer therapies such as radiation and chemotherapy, as well as immunotherapies. For R/R disease, treatments include PI3 kinase inhibitors, targeted therapies and immunomodulators. A different type of CAR-T therapy (Yescarta) was approved for R/R FL in 2021.
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Potential Benefits of CAR-T Therapy
In the last ten years, oncology researchers have made enormous progress in bring chimeric antigen receptor (CAR) T-cell therapies, more commonly known as CAR-T, to patients with different types of cancers. CAR-T is a type of immunotherapy in which the patients’ own T-cells are engineered to target and remove cancer cells. Six such therapies have been approved in the past five years to treat different types of blood cancers, including lymphoma, leukemia and myeloma.
CAR-T cells have been demonstrated to be very effective and provide favorable long-term outcomes; however, their cost and side effects have created a bit of hesitancy. Nonetheless, these therapies are now being more frequently incorporated into standard treatment, particularly for challenging cancers.
Kymriah Clinical Trial Results
Kymriah is a CD19-directed genetically modified autologous T-cell immunotherapy administered as a single, intravenous dose 0.6 to 6.0 x 108 CAR-positive viable T
cells. Data from a Phase II trial demonstrated that Kymriah was safe and effective in adults with R/R FL. The ELARA trial was a multicenter, single-arm, open-label trial in which 90 patients were administered Kymriah. These patients had previously received a median of four prior lines of therapy, with over half having received more than four lines; 79 percent were refractory to their last prior treatment.
Median time to response to therapy was 2.9 months, with an overall response rate of 86 percent at three months after infusion; 68 percent of patients achieved a complete response to therapy. Results from the trial also showed long-term benefits, as 85 percent of those who achieved an initial response continued to respond at 12 months.
Safety data were evaluated in 97 patients who were followed over a median of 21 months. Over half of these patients reported cytokine release syndrome, or CRS, and over 40 percent reported neurological events. In addition, the most common side effects included infections (pathogens unspecified), fatigue, musculoskeletal pain, headache and diarrhea.
Kymriah has previously been approved to treat patients up to 25 years of age with R/R B-cell precursor acute lymphoblastic leukemia (ALL) and for adult patients with R/R large B-cell lymphoma after two or more lines of systemic therapy. It carries a Black Box Warning for CRS and neurological toxicities. Novartis is currently investigating Kymriah for high-risk ALL, and is exploring additional targeted therapies for hematological cancers and solid tumors.
A New Option for R/R FL Patients
In the ELARA trial, 18 percent of patients received treatment in an outpatient setting. Therefore, Kymriah may be administered in a more flexible manner to potentially reduce treatment burden.
“The approval of Kymriah offers patients with relapsed or refractory follicular lymphoma a new treatment option and new hope for improving patient outcomes,” said Meghan Gutierrez, Chief Executive Officer at the Lymphoma Research Foundation, in the Novartis press release.
In addition to Kymriah, several other therapies are currently being investigated to treat R/R FL. These include treatments that have been approved for other cancer indications, such as Opdivo (nivolumab) and Imbruvica (ibrutinib), and novel candidates like buparlisib.