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Conference Coverage

Promising Efficacy of Frontline Nivolumab in Combination With R-CHOP for Patients With High-Risk DLBCL

Featuring Oluwatobi Odetola, MD

 

At the 2023 American Hematology Society (ASH) Meeting in San Diego, California, Oluwatobi Odetola, MD, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Maywood, Illinois, shared expert insights on a phase 1b study which demonstrated the promising efficacy of nivolumab in combination with R-CHOP among high-risk patients with diffuse large B-cell lymphoma (DLBCL). 

 

Transcript:

I am Oluwatobi Odetola. I'm a 3rd year hematology fellow at Northwestern University in Chicago, at the 65th annual ASH meeting 2023. I'll be presenting our research on a phase 1b clinical trial, evaluating the addition of nivolumab to [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone] (R-CHOP) in patients with high-risk diffuse large B-cell lymphoma. Our research is based on the finding that about 20% of diffuse large B-cell lymphomas have a PD-L1, PD-L2 mutation locus, and therefore warrant investigation of the use of immune checkpoint inhibitors in this patient population.

The primary endpoints of our study [were] to establish a maximum tolerated dose for nivolumab [and to] obtain preliminary findings on the efficacy of this combination of nivolumab and R-CHOP in our patients. We conducted this study in a Phase 1b version, with dose escalation of nivolumab to establish the maximum tolerated dose, and evaluate efficacy in these patients. We look to evaluate predictors for toxicity of nivolumab in this patient population.

We enrolled a total of 33 patients with newly diagnosed diffuse large B-cell lymphomas, but also included patients with transformed or other forms of high-risk B-cell lymphomas, including double-hit lymphomas. Of these 33 patients, 22 patients were evaluable for efficacy, and 25 patients were evaluable for toxicity. [The] majority of our patients, or close to half of our patients, did have high-risk lymphoma, as described earlier, with low-grade lymphoma transforming to high-grade lymphoma, or having MYC aberrancy.

Our findings suggested that 20 of our 22 patients achieve[d] complete remission with this combination, using a maximum tolerated dose of nivolumab of 240 milligrams every 3 weeks. In terms of results, 20 of our 22 patients achieved complement metabolic response at the end of the study. The 2 patients who did not achieve complement metabolic response did not relapse and went on to other therapies with achievement of complete remission. Of note, 1 of our patients died of COVID-19 after 4 cycles of therapy, however, was in complete metabolic response at that time.

In terms of toxicity, the most common toxicity seen with the combination [therapy] included fatigue and neutropenia. With respect to nivolumab, the most common adverse effects seen were immune checkpoint reactions, including infusion reactions, dermatitis, thyroiditis, and colitis. In terms of biological correlates for toxicity, we did find that an exhausted T-cell phenotype predicted for progression of disease in subsequent patients. Whereas patients who were enriched with T-regulatory cell fragility did not progress in our study. We also found that in predicting for toxicity, patients who had an exhausted T-cell phenotype, or a naive CD4 T-cell phenotype, or even increased circulating B-cell [had] a higher risk of toxicity in our study. None of our patients with high-risk disease relapsed in this study.

Our study shows promising efficacy for this combination of nivolumab and R-CHOP in patients with high-risk diffuse B-cell lymphoma. However, some of our biological correlates do suggest markers that could predict for risk of toxicity with this combination, and help guide patient selection in further studies for this combination.

 


Source:

Odetola O, Ma S, Winter J, et al. A phase Ib study to evaluate the safety and efficacy of nivolumab in combination with R-CHOP in high-risk DLBCL. Presented at the 2023 ASH Annual Meeting: December 9-12, 2023. San Diego, CA. Abstract 4462

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Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of OLN or HMP Global, their employees, and affiliates. 

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