Primary mediastinal B cell lymphoma (PMBCL) — a rare subtype of diffuse large B cell lymphoma — is very difficult to treat in the relapsed/refractory setting. A recent study showed, however, that pembrolizumab provides an objective response rate of 41%.1
PMBCL frequently exhibits an abnormality in chromosome 9, which is associated with copy number alterations and rearrangements of the PD-L1 and PD-L2 genes, leading to an overexpression of PD-L1 and PD-L2.
The efficacy and safety of pembrolizumab, a PD-1 inhibitor, were reported from an analysis of 18 patients enrolled in KEYNOTE 013 (ClinicalTrials.gov Identifier: NCT01953692), an ongoing phase 1 study for patients with hematologic malignancies.
The report indicated also that 61% of patients experienced drug-related adverse events, though these events were mostly grade 1 to 2 and generally manageable.
“These positive and interesting results show that pembrolizumab provides outcomes better than salvage therapy in patients with rrPMBCL [relapsed/refractory PMBCL],” Nadia Khan, MD, of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, told Cancer Therapy Advisor.
Dr Khan explained that although 80% to 90% of patients in this setting are cured using first-line therapy with DA EPOCH (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and DA-EPOCH with rituximab, it is much harder to eradicate disease in relapsed patients. “There are no proven best salvage therapies for these patients,” she said.
KEYNOTE 013 Results
Eleven patients with rrPMBCL received pembrolizumab 10 mg/kg every 2 weeks intravenously for the trial’s duration and, after a protocol amendment, 8 patients received a fixed dose of 200 mg every 3 weeks. Treatment continued up to 2 years, until unacceptable toxicity, or until confirmed disease progression. The median duration of follow up was 11.3 months.
Although 19 patients with rrPMBCL were enrolled in the study, by analysis cutoff date, 18 received 1 or more dose of the drug and 1 patient had not yet reached the first response assessment.
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In this heavily pretreated group of patients, pembrolizumab was the median fourth line of therapy.
In a safety analysis — a co-primary endpoint — the most common drug-related adverse events were hypothyroidism, diarrhea, nausea, fatigue, pyrexia, and decrease appetite (2 patients each). Grade 3 neutropenia was reported in 1 patient.