FDA Pushes Bristol Myers' BLA for CAR-T Drug to End of 2020
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New Jersey-based Bristol Myers Squibb announced on Wednesday that the U.S. Food and Drug Administration (FDA) has extended the action date of its biologics license application (BLA) for lisocabtagene maraleucel (liso-cel) by three months to November 16, 2020. The CD19-directed chimeric antigen receptor (CAR) T cell therapy is a treatment for adults with relapsed or refractory large B-cell lymphoma after at least two prior therapies.
Bristol Myers Squibb submitted additional information to the FDA, which will require more time for the FDA to review. The company also intends to work closely with the FDA to support the ongoing review of liso-cel.
On Monday, Healio reported that research from a Phase II study, which was presented at the American Association for Cancer Research Annual Meeting, showed treatment with atezolizumab after the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel (axi-cel) is safe and clinically effective for refractory diffuse large B cell lymphoma.
“Studies have shown that PD-1 is upregulated on CAR T cells and PD-L1 is upregulated on tumor cells and in most of the tumor microenvironment following CAR T-cell infusion,” Caron A. Jacobson, MD, medical director of the immune effector cell therapy program at Dana-Farber Cancer Institute, said during a presentation, according to Healio. “This upregulation may contribute to T-cell exhaustion and tumor cell immunization, leading to the hypothesis that checkpoint blockade may augment CAR T-cell activity.”
Adults with refractory diffuse large B cell lymphoma who received previous CD20-targeted therapy and an anthracycline-containing chemotherapy regimen were eligible for the Phase 2 study, known as ZUMA-6. Overall, the combination of axi-cel and atezolizumab appeared to be efficacious, with little or no safety issues. However, the findings still need to be evaluated in a larger randomized trial.
A study published in Hematological Oncology in April suggested that the presence of hypercalcemia when a patient is diagnosed with large B-cell lymphoma is associated with negative prognostic factors. Researchers drew their conclusions after analyzing 305 subjects with the condition between January 2006 and June 2018. In the end, hypercalcemia was associated with adverse prognostic factors in patients with de novo diffuse large B-cell lymphoma (DLBCL). These factors ultimately translated into lower event-free survival rates at 24 months, shorter progression-free survival and overall survival (median 4.7 years) in patients with lymphoma-related hypercalcemia.
The researchers also concluded that cancer-related hypercalcemia can present in nearly 30 percent of patients, especially with those with cancers such as renal cell carcinoma.
“In conclusion, our study, conducted on a homogeneous and routine clinical practice cohort of de novo DLBCL, demonstrates that hypercalcemia at diagnosis is strongly associated with adverse prognostic factors and a short diagnosis‐to treatment interval,” the authors concluded. “Its adverse impact on outcome appears to be closely linked to IPI parameters suggesting that hypercalcemia is rather a biomarker of the underlying biological aggressiveness of DLBCL.”
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma (NHL) in the world, according to the Lymphoma Research Foundation. It also accounts for about 22 percent of newly diagnosed cases of B-cell NHL in the U.S., with approximately 18,000 people diagnosed with it annually.
The condition can develop in the lymph nodes or other areas, such as the gastrointestinal tract, tests, thyroid, skin, breast or essentially any other organ of the body. Although it is aggressive, it is considered potentially curable.