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Tocilizumab manages adverse events following PD-1 blockade therapy
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CHICAGO — Tocilizumab appeared to be a viable therapeutic option for patients with lung cancer who experienced an immune-mediated adverse event following treatment with PD-1 checkpoint blockade, according to study results presented at International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology.
Despite their clinical benefit, immune checkpoint inhibitors can be associated with a variety of immune-mediated adverse events.
Corticosteroids are considered standard frontline treatment of these events, although the management of steroid-refractory events is poorly defined.
“There is a paucity of data on which consensus guidelines may be based,” Aparna Hegde, MD, chief research fellow at East Carolina University, said during the presentation. “Treatment with anti-IL-6 receptor monoclonal antibody, tocilizumab [Actemra, Genentech], led to improvement in systemic inflammatory response syndrome and immune-related adverse events in these patients. Hence, we adopted the use of tocilizumab as our standard of treatment for high-grade immune-related adverse events.”
Hegde and colleagues evaluated tocilizumab — an immunosuppressive drug — for the initial management of patients with immune-mediated adverse events following immune checkpoint inhibitor therapy for lung cancer treatment.
Among 87 patients treated with nivolumab (Opdivo, Bristol-Myers Squibb), 34 required treatment with tocilizumab (39.1%). These patients received 4 mg/kg tocilizumab IV over a 1-hour span.
All patients received corticosteroids (median dose, 60 mg prednisone equivalents).
Twenty-seven patients (79.4%) experienced clinical improvement, defined as resolution of symptoms or hospital discharge within 7 days. Median time to discharge was 4 days (range, 1-27).
At initial dose of tocilizumab, patients recorded a median C-reactive protein of 100.5 mg/L (range, 2-350.4).
Patients who received tocilizumab demonstrated no significant difference in median OS compared with patients who did not (6.1 months vs. 8.7 months).
The researchers noted a trend toward inferior OS among patients who required more than one dose of tocilizumab; however, this was not statistically significant (HR = 1.72; 95% CI, 0.87-3.37).
“Further multicenter randomized studies are needed to determine the definitive utility of tocilizumab and C-reactive protein as an accompanying biomarker in the management of high grade steroid-refractory immune-related adverse events,” Hedge said. – by Kristie L. Kahl
Reference:
Stroud CR, et al. Abstract OA03.05. Presented at: International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology; Sept. 14-16, 2017; Chicago.
Disclosure: Hegde reports no relevant financial disclosures.
Perspective
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Heather Wakelee, MD
This is a novel agent that has the potential utility to manage toxicity. That is important because, when you get beyond the steroids that we use as a first-line approach with a significant immune-related adverse event, there is not a whole lot else. Physicians have occasionally used mycophenolate; that might work sometimes, but it is all anecdotal. Physicians also have talked about giving IV immunoglobulin if patients have been through the other options, and that is also anecdotal. There is a clear, unmet need here. But, we have work to do.
This is a potential therapeutic option for immune-related adverse events. C-reactive protein may have clinical utility in monitoring the response. However, we really need to know what that looks like in patients who are treated with other modalities before we can claim this as an approach.
The researchers said there were no adverse events. With the decrease in OS, it may be that those patients were having other problems, but we need to clarify that.
We need to take this and move it into multicenter, randomized study to see if this is really a pharmaceutical intervention that is helpful. I commend the authors for thinking about this and coming up with a novel strategy, but we need to look at it within the context of a clinical trial before we can be discussing this as a good thing to be doing.
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