Nivolumab-Based Treatment Effective for Early Unfavorable Classic Hodgkin Lymphoma

By Will Boggs MD

May 07, 2020

NEW YORK (Reuters Health) - The anti-PD-1 antibody nivolumab, along with doxorubicin, vinblastine and dacarbazine, provides high remission rates in patients with early-stage unfavorable classic Hodgkin lymphoma (HL), according to results from the phase-2 NIVAHL trial.

"Anti-PD-1-based first-line treatment should be further investigated to ultimately achieve the long ongoing quest of maintaining the excellent cure rates with less treatment-related morbidity in HL," Dr. Paul J. Broeckelmann of the University of Cologne, in Germany, told Reuters Health by email.

The anti-PD-1 antibodies nivolumab and pembrolizumab have provided unprecedented response durations and sustained progression-free survival (PFS) in patients with relapsed classic HL who achieve complete remission.

Dr. Broeckelmann and colleagues in the NIVAHL trial investigated the efficacy, safety, and feasibility of two nivolumab-based regimens in 109 patients with early-stage unfavorable classic HL.

Fifty-four patients were randomly assigned to concomitant therapy with nivolumab and AVD (N-AVD) on day 1 and 15 of each 28-day cycle for four cycles, and 55 patients to sequential therapy starting with four infusions of nivolumab in 14-day intervals followed by two 28-day cycles of N-AVD and two 28-day cycles of AVD.

At the first interim restaging (after two cycles of N-AVD or four doses of nivolumab), all 54 patients in the concomitant group and 49 of 51 eligible patients in the sequential group achieved objective responses, including 47 (87%) and 26 (51%) patients, respectively, who had complete remissions.

At the end of systemic treatment, objective responses were observed in all 54 concomitant patients (45 with complete remission) and in 50 (98%) sequential patients (43 with complete remission), the researchers report in JAMA Oncology.

With a median follow-up of 14 months in the concomitant group and 13 months in the sequential group, 12-month PFS was 100% for concomitant and 98% for sequential treatment. Overall survival at 12 months was 100% in both treatment groups.

In both groups, 98% of patients had treatment-related adverse events, with treatment-related adverse events of grade 3 or greater in 76% of patients in the concomitant group and 80% of patients in the sequential group. During nivolumab monotherapy in the sequential treatment group, 87% of patients had an adverse event.

"In my opinion, the previously unreported very high complete remission rate of >50% at first interim restaging after 4x nivolumab monotherapy is thrilling," Dr. Broeckelmann said. "This finding warrants further investigation, in addition to the combined immunochemotherapy, to evaluate first-line anti-PD-1 monotherapy in curative intent in selected HL patients."

"The investigator-sponsored NIVAHL trial is the first ever to investigate two different anti-PD-1-based first-line treatments of early-stage unfavorable HL," he said. "A comprehensive set of correlative studies on sequential blood and tumor samples is ongoing to decipher mechanisms underlying efficacy, resistance, and immune-related toxicities."

Dr. Stephen M. Ansell of Mayo Clinic, in Rochester, Minnesota, who has studied the use of nivolumab for relapsed/refractory classic Hodgkin lymphoma, told Reuters Health by email, "These excellent results are similar to the findings with the same combination in patients with advanced-stage Hodgkin lymphoma, in that the regimen is very efficacious and the treatment was well tolerated."

"The interesting finding is that nivolumab monotherapy, prior to chemotherapy being given, resulted in a 96% objective response rate and a 51% complete response rate in these early-stage disease patients," he said. "This may allow us to give less chemotherapy and radiation therapy to patients in the future."

"The addition of nivolumab to the combination also allows for the omission of bleomycin, a drug with increased risk of substantial pulmonary toxicity," said Dr. Ansell, who was not involved in the new research.

He added that the results should be confirmed in further trials. "A randomized study is in progress in advanced-stage patients, and a similar study should be conducted in limited-stage disease."

Bristol-Myers Squibb provided the study drug nivolumab, as well as financial support, and had various relationships with several of the authors, including Dr. Broeckelmann.

SOURCE: JAMA Oncology, April 30, 2020.