Nivolumab Demonstrates Activity in Hematologic Cancers

The anti–PD-1 (programmed death 1) antibody nivolumab has shown activity in hematologic cancers, according to two presentations at the 2014 American Society of Hematology (ASH) Annual Meeting, held December 6–9 in San Francisco.

Nivolumab is also being developed in solid tumors where the antibody has demonstrated significant efficacy in non–small-cell lung cancer and melanoma. Nivolumab has received a priority review by the US Food and Drug Administration (FDA) for pretreated metastatic melanoma patients.

In the first presentation, of 23 patients with relapsed Hodgkin lymphoma, most of whom failed three or more prior therapies including autologous stem cell transplant and brentuximab vedotin, 87% (20 patients) responded to nivolumab. Seventeen percent had a complete response and 70% had a partial response after a median follow-up of 40 weeks. The 24-week progression-free survival rate was 86%.

“These preliminary results of 87% overall response is quite high in a group of patients, all of whom are heavily pretreated,” said study presenter and senior author Philippe Armand, MD, PhD, of Dana-Farber Cancer Institute in Boston.

Sixty percent of patients responded by week 8 of treatment; 48% of patients continue to respond and participate in the trial.

Grade 3 adverse events were experienced by 22% of patients, and included pneumonitis, gastrointestinal inflammation, leukopenia, and increased lipase level. There were no grade 4 events or any treatment-related deaths on study.

These Hodgkin lymphoma patients were treated with 3-mg/kg nivolumab every 2 weeks as part of an expansion cohort in the larger phase I dose-escalation trial (NCT01592370) that will include a cohort of patients receiving the combination of nivolumab and another immunotherapy, the anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) antibody ipilimumab.

The median age of patients was 35. Eighteen patients (78%) had undergone an autologous stem cell transplant, seven patients (30%) had four or five prior therapies, and eight patients (35%) underwent six or more prior therapies.

All patients tested had an abnormality on chromosome 9 that led to an overexpression of programmed death-ligand 1 (PD-L1) on patients’ tumors. “This supports the hypothesis that classical Hodgkin lymphoma appears to be a tumor with genetically determined vulnerability to PD-1 blockade,” said Armand. “We hope that anti–PD-1 blockade, in the future, will become an important part of the treatment of patients with classical Hodgkin lymphoma.”

These results were also published in the New England Journal of Medicine.

Based on these early results, nivolumab has been granted a breakthrough therapy designation from the FDA. A phase II registration trial (CheckMate 205; NCT02181738) in patients who have failed on an autologous stem cell transplant has already been initiated.

Another presentation of preliminary results from the same phase I hematologic malignancy trial demonstrated that nivolumab had activity in B-cell non-Hodgkin lymphoma (36% overall response among 29 patients), as well as in T-cell non-Hodgkin lymphoma (17% overall response, all partial responses, in 23 patients). Of those with B-cell non-Hodgkin lymphoma, three patients with diffuse large B-cell lymphoma (DLBCL) and three patients with follicular lymphoma (FL) responded to the treatment. Of the T-cell non-Hodgkin lymphoma patients, two with peripheral T-cell lymphoma and one with another type of T-cell lymphoma responded. There were no responses among the 27 patients with multiple myeloma in the study. A phase II study in DLBCL and FL is currently ongoing (CheckMate 140; NCT02038946).