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Combination Therapy With Immunochemotherapy and an Antibody-Drug Conjugate in DLBCL


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As reported in The Lancet Oncology, Hervé Tilly, MD, and colleagues found that the combination of polatuzumab vedotin, an antibody-drug conjugate targeting the CD79b component of the B-cell receptor, with immunochemotherapy showed high response rates in the phase II portion of a phase I/II study in previously untreated diffuse large B-cell lymphoma.

Hervé Tilly, MD

Hervé Tilly, MD

The phase II expansion of the study (conducted at 11 sites in the United States and France) included 66 patients with newly diagnosed disease. Patients received the polatuzumab vedotin recommended phase II dose of 1.8 mg/kg on day 2 of cycles 1 and 2 and on day 1 of subsequent 21-day cycles in combination with R-CHP (rituximab plus cyclophosphamide, doxorubicin, and prednisone; n = 45) or obinutuzumab plus CHP (G-CHP; n = 21) for a total of 6 or 8 cycles according to investigator preference.

Adverse Events

Among the patients receiving the phase II dose of polatuzumab vedotin, the most common adverse events of grade ≥ 3 were neutropenia (30%), febrile neutropenia (18%), and thrombocytopenia (9%). Grade 1, 2, and 3 peripheral neuropathy were observed in 27%, 11%, and 3% of patients. Two treatment-related deaths were reported—one due to complications of atrial fibrillation, and one due to septic shock.

Response Rates

Among the 66 patients receiving the phase II dose, at median follow-up of 21.5 months, 59 patients (89%) had an objective response, including a complete response in 51 (77%). Responses were observed in 40 (89%) of 45 patients receiving polatuzumab vedotin plus R-CHP and 19 (90%) of 21 receiving polatuzumab vedotin plus G-CHP. Among all 66 patients, 12-month progression-free survival was 91%, and 24-month progression-free survival was 83%.

The investigators concluded: “The safety of incorporating polatuzumab vedotin to R-CHP or G-CHP was as expected and manageable. Preliminary clinical activity in newly diagnosed diffuse large B-cell lymphoma seems promising and encouraged a phase III trial comparing polatuzumab vedotin with R-CHP to R-CHOP.” 

Tilly H, et al: Lancet Oncol. May 14, 2019 (early release online).


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