Study of Single-Agent Nivolumab in Patients With Relapsed/Refractory DLBCL Fails to Meet Endpoint

Treatment with single-agent nivolumab was associated with “disappointingly low” response rates in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to results from a phase II trial published in the Journal of Clinical Oncology.

Nivolumab, an anti–PD-1 monoclonal antibody, initially demonstrated a promising preliminary response rate in earlier phase I trials, but the drug failed to meet its primary endpoint in the phase II trial, suggesting that patients with relapsed/ refractory disease or who are ineligible for transplant may fare better with other treatment approaches.

In this open-label trial, the authors, led by Stephen Ansell, MD, PhD, from the Mayo Clinic in Rochester, Minnesota, evaluated nivolumab 3 mg/kg (administered intravenously over 60 minutes, every 2 weeks) in 121 patients. Participants had failed treatment with autologous hematopoietic cell transplantation (n=87) or were ineligible for transplantation (n=34). The researchers observed that patients in the prior transplant group were young and had higher baseline performance status scores than those who were ineligible for transplant. The median number of prior lines of therapy was three in each group (range not provided).

After a median follow-up of nine months (range = 0.1-2.5 months) in the prior-transplant group and six months (range = 0.2-2.4 months) in the transplant-ineligible group, the overall response rates (defined as partial remission or better) were 10 percent and 3 percent, respectively. The median durations of response were 11 and eight months (ranges not reported).

Three patients (all of whom were in the prior-transplant group) achieved a complete remission that lasted for at least 11 months, the authors added. In the transplant-ineligible group, the best response was in one patient who achieved a partial remission that lasted for 8.3 months.

Patients in the prior-transplant group also appeared to have better efficacy outcomes in terms of median progression-free survival (1.9 months vs. 1.4 months) and median overall survival (12.2 months vs. 5.8 months; p values not reported).

The researchers also attempted to assess outcomes with nivolumab for patients with genetic alterations in 9p24.1, a potential biomarker indicating disease that is likely to respond to PD-1 blockade, but these mutations were infrequent in this population.

Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification.

Seventy-eight patients died during the study, although none of the deaths were attributed to nivolumab treatment.

Given the negative results in this study, the researchers concluded that future studies should focus on combinations of immunotherapies, beyond PD-1 blockade alone. As a limitation of the study, the authors noted that this was a small population, with a small proportion of patients with the 9p24.1 genetic alteration, who are more likely to benefit from PD-1-inhibitor treatment.

The authors report relationships with Bristol-Myers Squibb, the manufacturer of nivolumab, which sponsored the trial.


Ansell SM, Minnema MC, Johnson P, et al. Nivolumab for relapsed/refractory diffuse large B-cell lymphoma in patients ineligible for or having failed autologous transplantation: a single-arm, phase II study. J Clin Oncol. 2019;37:481-489.