Patients with classical Hodgkin’s lymphoma who progressed after receiving autologous hematopoietic stem cell transplant (HSCT) and treatment with Adcetris (brentuximab vedotin) may benefit from the PD-1 inhibitor Opdivo (nivolumab), according to the results of a Phase 2 clinical trial.
The study, “Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial,” published in The Lancet Oncology, shows that Opdivo might be a new treatment option for patients with a high unmet need.
The current standard of care for patients with classical Hodgkin’s lymphoma is high-dose chemotherapy followed by HSCT. However, nearly half these patients relapse following HSCT and require additional treatments. Adcetris has emerged as a good therapeutic option, increasing overall survival (OS) and progression-free survival (PFS) in these patients. Still, some who were treated with both HSCT and Adcetris relapse, and no current treatment options exist.
Because Hodgkin’s lymphoma cells have been shown to upregulate PD-1 ligands, the researchers hypothesized that treating these patients with an inhibitor of the PD-1 pathway, such as Opdivo, could improve their outcomes. Activation of the PD-1 pathway in immune cells is known to impair them from recognizing and attacking tumor cells. So, inhibiting this pathway removes the breaks from the immune system, allowing for a more efficient immune response to tumors.
The study (NCT02181738) enrolled 80 patients with Hodgkin’s lymphoma who had failed to respond to HSCT and had either relapsed after or failed to respond to Adcetris. They were treated with Opdivo intravenously every two weeks until progression, death, unacceptable toxicity, or withdrawal from the study. The study’s primary endpoint was an objective response in a follow-up after at least six months.
After a median follow-up of 8.9 months, 53 patients achieved a confirmed objective response, accounting for an overall response rate (ORR) of 66.3%. Among those who responded to Opdivo, seven had a complete remission and 46 showed a partial remission. All but one patient exhibited a tumor reduction of at least 50 percent.
The six-month PFS was 76.9%, and the six-month overall survival was 98.7 percent. Nonetheless, 11 responders, one complete and 10 partial, still showed diseased progression after a median duration of 7.8 months.
The most common drug-related adverse events included fatigue, infusion-related reaction, and rash. In addition, the most common severe adverse event was fever, but other serious adverse events included neutropenia and increase lipase concentrations. Although three patients died during the study, the researchers believe that none of these deaths were treatment related.
“We are in the initial stages of assessing immune checkpoint inhibitors in classical Hodgkin’s lymphoma, which illustrate the role of immunoreactive cells when directed against neoplastic cells,” Dr. Christian Gisselbrecht, MD, professor of hematology at Paris Diderot University and section head of lymphoma and myeloma at Hôpital Saint-Louis, wrote in an accompanying editorial.
“Randomized studies comparing nivolumab and brentuximab vedotin, nivolumab alone, and the investigator’s treatment choice after autologous HSCT are warranted to confirm long-term efficacy and safety of nivolumab in patients with classical Hodgkin lymphoma,” he wrote.