Nivolumab induced responses in patients with classical Hodgkin lymphoma who progressed following autologous hematopoietic stem cell transplantation and treatment with brentuximab vedotin, according to results of a single-arm, phase 2 study.
Nivolumab (Opdivo, Bristol-Myers Squibb) also demonstrated a tolerable safety profile.
Anas Younes, MD, chief of lymphoma service at Memorial Sloan Kettering Cancer Center, and colleagues previously conducted a phase 1B study that showed nivolumab produced a high response rate in patients with relapsed and refractory classical Hodgkin lymphoma.
However, the clinical safety and efficacy of nivolumab remained unstudied among patients who experienced failure following HSCT and brentuximab vedotin (Adcetris, Seattle Genetics).
“For patients who progress after autologous HSCT and brentuximab vedotin, no standard treatment options exist at present,” Younes and colleagues wrote. “Thus, an unmet medical need for effective therapies persists in this patient population.”
The analysis included data from 80 patients (median age, 37 years; range, 28-48; median prior therapies, 4) who received 3 mg/kg IV nivolumab over 60 minutes every 2 weeks for up to 6 months, or until progression, death or unacceptable toxicity.
Median follow-up was 8.9 months (interquartile range [IQR], 7.8-9.9).
Fifty-three patients achieved an independently confirmed objective response, resulting in an ORR of 66.3% (95% CI, 54.8-76.4).
Seven patients achieved complete remission and 46 patients achieved partial remission. All but one responder had a tumor reduction of at least 50%.
Responders had a median time to first objective response of 2.1 months (IQR, 1.9-3), with 58% (n = 1) achieving a response by the time of their first scan.
Eleven responders (complete, n = 1; partial, n = 10) experienced progressive disease after a median duration of response of 7.8 months (95% CI, 6.6-not reached).
The rate of 6-month PFS was 76.9% (95% CI, 64.9-85.3) and 6-month OS was 98.7% (95% CI, 91-99.8).
Fifty-one patients (64%) remained on treatment at the time of this analysis.
Commonly observed adverse events included fatigue (25%), infusion-related reactions (20%) and rash (16%). Grade 3 or grade 4 adverse events included neutropenia (5%), and increased lipase concentrations (5%). The most common serious adverse event of any grade was pyrexia (4%).
Three patients died during the study, although no deaths were considered treatment related.
The researchers acknowledged the use of a single-arm study design — due to the lack of an improved therapy to use as a control — as a limitation to these results.
Because of the study’s short follow-up period, longer follow-up will be needed to assess response durability, according to the researchers.
“In this registrational study, nivolumab represents a therapeutic approach with durable responses and an acceptable safety profile, relative to standard chemotherapeutics,” Younes and colleagues wrote. “The inclusion of additional patient cohorts in this ongoing multicohort trial — for example, patients who are brentuximab vedotin–naive or patients who might have received brentuximab vedotin either before or after autologous HSCT — will further define the role of nivolumab in classical Hodgkin lymphoma, and could potentially contribute to transforming the treatment landscape for this disease.”
It remains to be seen whether patients treated with nivolumab could eventually proceed to allogeneic HSCT, 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.
“In Younes and colleagues’ study, five patients had allogeneic transplantation and were alive without severe graft-versus-host disease, but contrast with the results of a phase 1 trial with nivolumab in which four of five patients who had an allogeneic HSCT died from treatment-related mortality,” Gisselbrecht wrote. “At the time of drug approval, the FDA issued a special warning to closely follow patients given allogeneic HSCT to monitor immune-mediated adverse reactions.”
Further study of nivolumab is needed in this patient population, according to Gisselbrecht.
“We are in the initial stages of assessing immune checkpoint inhibitors in classical Hodgkin lymphoma, which illustrate the role of immunoreactive cells when directed against neoplastic cells,” Gisselbrecht wrote. “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.” – by Cameron Kelsall
Disclosure: Bristol-Myers Squibb funded this research. Younes reports research funding and/or honoraria from Bayer, Bristol-Myers Squibb, Celgene, Curis, Incyte, Janssen R&D, Johnson and Johnson, Merck, Novartis, Roche, Sanofi and Seattle Genetics. Please see the full study for a list of all other researchers’ relevant financial disclosures. Gisselbrecht reports no relevant financial disclosures.