FDA News

FDA expands approval of Kymriah to include relapsed or refractory large B-cell lymphoma

The FDA expanded the approval of tisagenlecleucel to include treatment of patients with relapsed or refractory large B-cell lymphoma, according to the agent’s manufacturer.

The approval applies to use of tisagenlecleucel (Kymriah, Novartis) — a chimeric antigen receptor (CAR) T-cell therapy — for patients with diffuse large B-cell lymphoma, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma who received two or more lines of systemic therapy.

Tisagenlecleucel — developed by Novartis in collaboration with University of Pennsylvania — is not indicated for treatment of patients with primary central nervous system lymphoma.

“The goal of Kymriah is to provide physicians with a therapy that has demonstrated durable response rates in relapsed or refractory DLBCL patients, a patient population that has endured multiple rounds of chemotherapy with many having experienced unsuccessful stem cell transplants,” Stephen J. Schuster, MD, Robert and Margarita Louis-Dreyfus professor in chronic lymphocytic leukemia and lymphoma clinical care and research at Penn’s Perelman School of Medicine and director of the lymphoma program at Abramson Cancer Center, said in a Novartis-issued press release. “With this approval, physicians now have a meaningful therapeutic option that can achieve and maintain a sustained response without stem cell transplant along with a consistent safety profile.”

Tisagenlecleucel is the only CAR T-cell therapy to receive FDA approval for two distinct indications.

In August, the FDA approved the agent for treatment of patients aged 25 years or younger with B-cell precursor acute lymphoblastic leukemia that is refractory or in second relapse.

The FDA based the expanded approval on results of the pivotal phase 2 JULIET study, the first multicenter, global registration study of tisagenlecleucel for adults with relapsed or refractory DLBCL.

The efficacy analysis included 68 evaluable patients. Results showed a 50% (95% CI, 38-62) overall response rate, a 32% complete response rate and an 18% partial response rate. Median duration of response had not been reached.

The Novartis-sponsored study included 106 patients who underwent infusion.

Adverse events that occurred among more than 20% of infused patients included cytokine release syndrome, infections, pyrexia, diarrhea, nausea, fatigue, hypotension, edema and headache.

Approximately one in five (23%) developed grade 3 or grade 4 cytokine release syndrome, 18% experienced grade 3 or grade 4 neurologic events, and 11% experienced severe or life-threatening encephalopathy.

One-quarter (25%) of patients developed grade 3 or grade 4 infections. Grade 3 or grade 4 cytopenias lasting more than 28 days included thrombocytopenia (40%) and neutropenia (25%).

No deaths occurred due to neurological events, and no fatal cases of cerebral edema occurred.

“[This] 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,” Liz Barrett, CEO of Novartis Oncology, said in the press release. “We look forward to leveraging all of our learnings and new capabilities from the initial launch of Kymriah in pediatric and young adult B-cell ALL for this larger group of patients.”

The FDA expanded the approval of tisagenlecleucel to include treatment of patients with relapsed or refractory large B-cell lymphoma, according to the agent’s manufacturer.

The approval applies to use of tisagenlecleucel (Kymriah, Novartis) — a chimeric antigen receptor (CAR) T-cell therapy — for patients with diffuse large B-cell lymphoma, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma who received two or more lines of systemic therapy.

Tisagenlecleucel — developed by Novartis in collaboration with University of Pennsylvania — is not indicated for treatment of patients with primary central nervous system lymphoma.

“The goal of Kymriah is to provide physicians with a therapy that has demonstrated durable response rates in relapsed or refractory DLBCL patients, a patient population that has endured multiple rounds of chemotherapy with many having experienced unsuccessful stem cell transplants,” Stephen J. Schuster, MD, Robert and Margarita Louis-Dreyfus professor in chronic lymphocytic leukemia and lymphoma clinical care and research at Penn’s Perelman School of Medicine and director of the lymphoma program at Abramson Cancer Center, said in a Novartis-issued press release. “With this approval, physicians now have a meaningful therapeutic option that can achieve and maintain a sustained response without stem cell transplant along with a consistent safety profile.”

Tisagenlecleucel is the only CAR T-cell therapy to receive FDA approval for two distinct indications.

In August, the FDA approved the agent for treatment of patients aged 25 years or younger with B-cell precursor acute lymphoblastic leukemia that is refractory or in second relapse.

The FDA based the expanded approval on results of the pivotal phase 2 JULIET study, the first multicenter, global registration study of tisagenlecleucel for adults with relapsed or refractory DLBCL.

The efficacy analysis included 68 evaluable patients. Results showed a 50% (95% CI, 38-62) overall response rate, a 32% complete response rate and an 18% partial response rate. Median duration of response had not been reached.

The Novartis-sponsored study included 106 patients who underwent infusion.

Adverse events that occurred among more than 20% of infused patients included cytokine release syndrome, infections, pyrexia, diarrhea, nausea, fatigue, hypotension, edema and headache.

Approximately one in five (23%) developed grade 3 or grade 4 cytokine release syndrome, 18% experienced grade 3 or grade 4 neurologic events, and 11% experienced severe or life-threatening encephalopathy.

One-quarter (25%) of patients developed grade 3 or grade 4 infections. Grade 3 or grade 4 cytopenias lasting more than 28 days included thrombocytopenia (40%) and neutropenia (25%).

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No deaths occurred due to neurological events, and no fatal cases of cerebral edema occurred.

“[This] 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,” Liz Barrett, CEO of Novartis Oncology, said in the press release. “We look forward to leveraging all of our learnings and new capabilities from the initial launch of Kymriah in pediatric and young adult B-cell ALL for this larger group of patients.”

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