January 17, 2014

Tony Berberabe, MPH

The anti-PD-1 monoclonal antibody pidilizumab showed promising clinical activity and was safely administered to patients with diffuse large B-cell lymphoma after autologous hematopoietic stem-cell transplantation.

Leo I. Gordon, MD

Pidilizumab, an anti-PD-1 monoclonal antibody, had promising clinical activity and was safely administered to patients with diffuse large B-cell lymphoma (DLBCL) after autologous hematopoietic stem-cell transplantation (AHSCT), according to data from a phase II trial.

“We think that the approach of disabling immune tolerance at a time when the immune system is remodeling, that is, after stem cell transplantation, is novel and affords an opportunity to enhance remission after stem cell transplant for large cell lymphoma,” said senior investigator Leo I. Gordon, MD, FACP, the Abby and John Friend Professor of Cancer Research, professor of Medicine, Director Lymphoma Program, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine.

In the study, 66 patients were eligible for treatment at 30 centers in the United States, Israel, Chile, and India. They received pidilizumab intravenously at a dose of 1.5 mg/kg every 42 days for three cycles, beginning 30 to 90 days from AHSCT. The primary end point was the 16-month progressionfree proportion from the time of first pidilizumab administration among all eligible patients who received at least one dose of the agent. Safety and toxicity, progression-free survival (PFS), overall survival (OS), immunogenicity of pidilizumab, and immune subset analyses were secondary end points.

Sixteen months after the first treatment, PFS was 72% (90% CI, 0.60-0.82) in the 66 eligible patients, meeting the primary end point. These findings compare favorably to two recent multicenter randomized clinical trials in this population, the researchers noted.

Among the 24 high-risk patients who remained PET-positive at the conclusion of salvage therapy, the 16-month PFS was 70% (90% CI, 0.51-0.82). Among 35 patients with measureable disease after AHSCT, the overall response rate after pidilizumab therapy was 51%.

The researchers noted that 24 hours after first treatment patients exhibited a significant increase in the number of PD-L1 bearing activated helper T-cells. This increase was sustained for at least 16 weeks. In addition, they noted changes in PD-1 ligand-bearing monocytes. They reported that the mean percentage increase was larger than the median increase at all time points, suggesting that “pidilizumab induced large increases in those cells that were early and sustained, but restricted to a subset of patients.”

Pidilizumab Phase II DLBCLa Data

PFS 16 months after first treatment

72%

Grade 3/4 neutropenia

19%

Grade 3/4 thrombocytopenia

8%

Pidilizumab, is an anti-PD-1 monoclonal antibody.

aOverall study included 72 patients with DLBCL undergoing AHSCT. AHSCT indicates autologous hematopoietic stem-cell transplantation; DLBCL, diffuse large B-cell lymphoma; PFS, progression-free survival.

Among all 72 patients who received at least one dose of pidilizumab, 96% experienced adverse events (AEs). Of the 613 AEs reported, the most frequently reported grade 3/4 AEs were neutropenia (19% of patients) and thrombocytopenia (8%). The researchers reported that all patients who had grade 4 neutropenia responded to growth factor treatment and remained asymptomatic.

The researchers concluded that PD-1 blockade is a viable therapeutic option in a high-risk subset of patients with residual disease. It may also overcome the negative prognostic value of a pretransplant positive PET scan.

“Further studies using this approach are warranted and our initial observations should be confirmed in a phase III randomized trial,” said Gordon.

Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013;31(33):4199-4206