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FDA approves Keytruda for primary mediastinal large B-cell lymphoma
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The FDA expanded the approval of pembrolizumab to include the treatment of adult and pediatric patients with primary mediastinal large B-cell lymphoma who have refractory disease or who relapsed after two or more prior lines of therapy.
Pembrolizumab (Keytruda, Merck) is the first anti-PD-1 therapy to be approved for the treatment of primary mediastinal large B-cell lymphoma. The FDA approved this indication under accelerated review.
The FDA based this approval for patients with primary mediastinal large B-cell lymphoma on data from the KEYNOTE-170 trial. This multicenter, open-label, single-arm trial assessed pembrolizumab among 53 patients (mean age, 33 years; 43% men; 92% white) with relapsed or refractory primary mediastinal large B-cell lymphoma.
Exclusion criteria included active noninfectious pneumonitis, active autoimmune disease, a medical condition that required immunosuppression, an active infection requiring systemic therapy or allogeneic hematopoietic stem cell transplantation within the past 5 years — or more than 5 years but with symptoms of graft-versus-host disease.
Researchers observed an overall response rate of 45% (95% CI, 32-60). Eleven percent of patients achieved a complete response and 34% achieved a partial response.
Median duration of response was not reached among the 24 patients who responded (range, 1.1+ to 19.2+).
Median time to complete or partial response was 2.8 months (range, 2.1 to 8.5) among the 24 responders.
Due to a lack of data among children, researchers extrapolated data from the adult primary mediastinal large B-cell lymphoma population. In another study of children with advanced melanoma, lymphoma or solid tumors, researchers administered a smaller dose of pembrolizumab. However, researchers observed more toxicities among pediatric patients compared with adults younger than 65 years.
“Relapsed or refractory primary mediastinal large B-cell lymphoma is often a challenging disease to treat and many affected patients are young adults,” Philippe Armand, MD, PhD, medical oncologist in the hematologic oncology treatment center at Dana-Farber Cancer Institute, said in a press release. “In the clinical trial that supported this approval, treatment with Keytruda resulted in meaningful responses, including complete disease remission in some patients. This approval, therefore, provides another therapeutic option for patients with primary mediastinal large B-cell lymphoma who have progressed on or after prior therapies.”
Pembrolizumab is not recommended for patients who require urgent cytoreductive therapy.
Eight percent of patients discontinued treatment with pembrolizumab due to adverse reactions, and 15% of patients interrupted treatment. Twenty-five percent of patients had an adverse event that required systemic corticosteroid therapy.
Serious adverse reactions occurred among 26% of patients. The most common serious adverse reactions included arrhythmia (4%), cardiac tamponade, myocardial infarction, pericardial effusion and pericarditis (2% each). The most common adverse reactions included musculoskeletal pain (30%), upper respiratory tract infection (28%), pyrexia (28%), cough (26%), fatigue (23%) and dyspnea (21%). Six (11%) patients died within 30 days of start of treatment.
Pembrolizumab also is indicated for the treatment of certain patients with melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, urothelial carcinoma, gastric cancer and cervical cancer.