Pseudoprogression and cancer immunotherapy: A seven year retrospective study of rate, temporal course, and predictive markers in an Irish tertiary referral center.

Abstract

2651 Background: Immunotherapy is a relatively new treatment strategy which has achieved unprecedented clinical efficacy in many advanced malignancies. However, the pattern of tumour response to immunotherapy is distinct from other therapies and poses major challenges to clinicians. One such challenge is pseudoprogression. The aim of this study was to assess the current management of patients on immunotherapy with radiological evidence of disease progression at first restaging imaging in an Irish cancer centre, and to determine the rate, time course, and predictive markers of pseudoprogression in those patients treated beyond progression (TBP). Methods: Patients treated with immunotherapy for metastatic malignancy in MMUH between March 2013 and September 2020 were retrospectively drawn. Inclusion required follow-up restaging imaging every 4-12 weeks for the duration of treatment. Patterns of response during immunotherapy were established from radiology reports and categorized as stable (SD), response (R), mixed disease (MD), or progressive disease (PD). Pseudoprogression was defined as progression/ mixed disease at first restaging compared to baseline followed by subsequent response/stable disease. Results: The cohort of 228 patients was comprised of 80 NSCLC, 74 melanoma, 25 RCC, 19 gynaecological, 14 gastrointestinal, 6 breast, 1 ESSCLC, and 9 other cancer patients. Median age was 61.16 (IQR 49.47-69.44). Therapeutic agents were anti-PD1 alone (176) or in combination with targeted therapy (6) or CTLA4 (13), CTLA4 alone (15), and anti-PD-L1 alone (13) or in combination with chemotherapy (5). At first restaging, the number (%) classified as SD, R, MD, and PD, respectively, was 29 (12.8), 62 (27.2), 16 (7), and 76 (33.3). Treatment was stopped prior to restaging in 44 (19.3) cases. Of the 92 patients with mixed/ progressive disease, 41 were TBP and 51 were not treated beyond progression (NTBP). Evidence of radiological progression and worsening performance status (PS) were the most common reasons given by clinicians for NTBP. Of those TBP, 20 had subsequent response/stable disease, occurring at a median of 105.50 (range 58.0-420) days after the initial restaging scan and giving an overall pseudoprogression rate of 8.8%. At one year, 100% of the pseudoprogression group was alive. The neutrophil-lymphocyte ratio (NLR) was significantly lower in the pseudoprogression group compared to those with true progression (p = 0.006). There was no significant difference in performance status between the two groups. Conclusions: Pseudoprogression on cancer immunotherapy is real but uncommon, with an overall incidence of 8.8%. It can occur any time up to 420 days after initial progression and indicates a high likelihood of > 1 year survival. A low NLR may be a useful predictor of pseudoprogression but a technological solution is likely needed.