An Anti-CD79B Antibody–Drug Conjugate Is Active in Non-Hodgkin Lymphoma

Patients with B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) often experience tumor relapse, emphasizing the need for additional therapeutic strategies. Preclinical studies suggest that polatuzumab vedotin, an antibody–drug conjugate targeting the B-cell receptor component CD79B conjugated to the microtubule-disrupting agent monomethyl auristatin E, has antitumor activity in NHL. To evaluate the safety, tolerability, and preliminary activity of polatuzumab vedotin, Palanca-Wessels and colleagues performed a multicenter, open-label phase I study in 95 patients with relapsed or refractory NHL or CLL. Thirty-four patients with NHL and 18 patients with CLL were enrolled in dose-escalation cohorts to determine the maximum tolerated dose of polatuzumab vedotin. Subsequently, 45 patients with NHL were treated with polatuzumab vedotin at the recommended phase II dose in a single-agent expansion cohort, and nine patients with NHL received polatuzumab vedotin in combination with rituximab. Grade 3-4 adverse events, most commonly neutropenia, anemia, and peripheral sensory neuropathy, occurred in 26 (58%) of 45 patients with NHL treated at the recommended phase II dose and in seven (77%) of nine patients in the combination cohort. Objective responses were observed in 23 of 42 evaluable patients with NHL, including seven complete responses and 16 partial responses, and in seven of nine patients treated with polatuzumab vedotin and rituximab, including two complete responses and five partial responses. Specifically, objective responses were reported in 14 of 25 patients with diffuse large B-cell lymphoma, seven of 15 patients with indolent NHL, and two of two patients with mantle-cell lymphoma. In contrast, polatuzumab vedotin did not exhibit activity in patients with CLL, potentially due in part to faster clearance of the antibody–drug conjugate in these patients as compared with patients with NHL. These findings indicate that polatuzumab vedotin is safe and active in NHL and support ongoing phase II clinical trials in patients with B-cell lymphoma.

Palanca-Wessels MC, Czuczman M, Salles G, Assouline S, Sehn LH, Flinn I, et al. Safety and activity of the anti-CD79B antibody–drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase I study. Lancet Oncol 2015 Apr 26 [Epub ahead of print].

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