Atypical Response Patterns in Patients Treated With Nivolumab.

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OBJECTIVE. The purpose of this study is to assess the frequency of atypical response patterns in oncology patients treated with the programmed cell death protein-1 inhibitor nivolumab. MATERIALS AND METHODS. This retrospective study included 254 patients treated with nivolumab alone or in combination, from January 2013 through August 2017. A blinded reader prospectively assessed treatment response. Among 166 patients (65%) who experienced a clinical benefit (defined as stable disease, partial response, or complete response as the best response), four response patterns were identified: pattern 1 is a decrease or less than 20% increase in the sum of the longest dimension (SLD) without a return to below the nadir, pattern 2 is a 10-19% increase in SLD with a return to below the nadir, pattern 3 is a 20% or greater increase in SLD with a return to below the nadir (classic pseudoprogression), and pattern 4 is the development of new lesions with a decrease in SLD lasting through at least two consecutive scans. Patterns 2, 3, and 4 were defined as atypical response patterns. RESULTS. Of 166 patients who experienced a clinical benefit, pattern 1 was seen in 133 (80%), pattern 2 was seen in 15 (9%), pattern 3 was seen in two (1%), and pattern 4 was seen in 16 (10%) patients. Thus, atypical response patterns were seen in 33 (20%) patients who experienced a clinical benefit, including 25 of 91 (27%) taking nivolumab and ipilimumab combined, six of 46 (13%) taking nivolumab alone, and two of 29 (7%) taking a combination of nivolumab and another chemotherapeutic agent (p = 0.02). CONCLUSION. Although classic pseudoprogression was rare, an atypical response was seen in 20% of patients who experienced a clinical benefit, and a delayed response up to 24 months of therapy may be seen. Radiologists should be aware of these atypical patterns to avoid errors in response assessment.