Polatuzumab Vedotin Well Tolerated, Active In Non-Hodgkin’s Lymphoma Patients

A phase I trial reports promising safety and activity results for polatuzumab vedotin in patients with relapsed or refractory non-Hodgkin’s lymphoma

medwireNews: The Antibody–drug conjugate polatuzumab vedotin has a favourable toxicity profile and “encouraging” clinical activity in patients with relapsed or refractory non-Hodgkin’s lymphoma, researchers report.
“This study demonstrates the feasibility of antibody–drug conjugates to deliver cytotoxic chemotherapy to tumours”, write Maria Palanca-Wessels, from the Fred Hutchinson Cancer Research Center in Seattle, Washington, USA, and co-workers in The Lancet Oncology.

On the basis of data from the initial dose-escalation phase of the phase I trial, which included 34 patients with non-Hodgkin’s lymphoma, the team established a dose of 2.4 mg/kg every 3 weeks as the recommended phase II dose of polatuzumab vedotin in these patients.

A total of 45 non-Hodgkin’s lymphoma patients, 11 of whom were part of the dose-escalation cohort, were given the monomethyl auristatin E–anti-CD79B antibody conjugate, targeting the B-cell Antigen Receptor, at the recommended phase II dose. And a further nine patients were treated with the combination of polatuzumab vedotin and rituximab.

Adverse events of grade 3 or 4 occurred in 58% of participants given single agent polatuzumab vedotin and in 77% of those who received the combination treatment.

Neutropenia was the most common grade 3 or 4 toxicity in patients who received polatuzumab vedotin, either alone or together with rituximab, occurring in 40% and 56% of patients, respectively. And anaemia of grade 3 or 4 was observed in 11% of single agent-treated participants and in 22% of those in the combination therapy group.

Moreover, grade 3 or 4 peripheral sensory neuropathy was observed in 9% of patients treated with polatuzumab vedotin alone.

Eight patients, all with diffuse large B-cell lymphoma, died during the course of the study, with one of the deaths occurring in the combination treatment arm. Three deaths, two as a result of infections and one owing to worsening ascites, were attributed to study treatment.

After a median follow-up of 4.3 months, 23 of 42 patients in the single agent group achieved an objective response of which seven were complete responses and 16 were partial. Of those given combination therapy, two patients achieved a complete response, while five had a partial response.

Median progression-free survival was 5.7 months in the single agent group and 12.5 months in the combination treatment group, with response lasting a median of 6.2 and 12.3 months, respectively.

The response to polatuzumab vedotin is “encouraging” in light of the fact that the study participants “had advanced disease and were heavily pretreated”, say Maria Palanca-Wessels et al.

In a linked commentary, Soon Lim, from the National Cancer Centre in Singapore, writes: “Polatuzumab vedotin’s tolerable safety profile and potential for combination with rituximab makes it an ideal drug to bring forward to the first-line setting.”

Soon Lim also sees a role for antibody–drug conjugates in the relapsed setting suggesting that they could be “be incorporated into second-line chemotherapy regimens to improve salvage therapy and increase the proportion of patients who could receive autologous stem-cell transplantation.”

References

Palanca-Wessels MCA, Czuczman M, Salles G, 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 1 study. Lancet Oncol 2015; Advance online publication 26 April. doi:10.1016/S1470-2045(15)70128-2

Lim ST. Antibody–drug conjugates in non-Hodgkin lymphoma. Lancet Oncol 2015; Advance online publication 26 April. doi:10.1016/S1470-2045(15)70161-0

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