Atypical Response Patterns in Patients Treated With Nivolumab.

Abstract

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.