Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

This pilot phase I trial studies the side effects of pembrolizumab and combination chemotherapy in treating patients with previously untreated diffuse large B-cell lymphoma or grade 3b follicular lymphoma. Monoclonal antibodies, such as pembrolizumab and rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab together with combination chemotherapy may be with a better treatment for diffuse large B-cell lymphoma or follicular lymphoma.

PRIMARY OBJECTIVES: I. To measure the toxicity profile of pembrolizumab (MK-3475) when co-administered with full-course RCHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) in subjects with previously untreated diffuse large B-cell lymphoma (DLBCL). SECONDARY OBJECTIVES: I. To assess clinical outcomes including response rate, event-free survival, and overall survival after MK-3475 + RCHOP induction for subjects with previously untreated DLBCL. TERTIARY OBJECTIVES: I. To measure baseline expression of proteins in the programmed death-1 (PD-1) family on tumor cells and coexisting immune infiltrates, using archival tissue when available. II. To measure peripheral blood T cell subsets before and after treatment using flow cytometry, and to measure baseline vitamin D (25-hydroxy, total). III. To explore relationships with these parameters and likelihood of response to therapy and outcomes. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and prednisone orally (PO) on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of the study treatment, patients are followed up to 5 years.