ABSTRACT
INTRODUCTION: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. METHODS: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). RESULTS: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79-19.15) months, and the six and 12-month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06 months (95% CI: 3.42-6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). CONCLUSION: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors.
ABSTRACT
BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICPi) may cause acute kidney injury (AKI) and their use is increasing. MATERIALS AND METHODS: This is a single-center retrospective cohort study of patients receiving ICPi drugs for solid organ malignancies. ICPi-related AKI, the need for renal replacement therapy during or following ICPi treatment, and the associated mortality was studied. RESULTS: Two hundred thirty five patients were included in the final analysis. Patients with (N = 40) and without (n = 195) AKI had similar age, sex, type of ICPi, baseline serum creatinine levels, comorbidities and mortality; while patients with AKI were more likely to be receiving a nephrotoxic agent or be treated for genitourinary malignancy. 18 patients had ICPi-related AKI; 7 of these patients underwent kidney biopsy, which showed acute interstitial nephritis while the remaining 11 were diagnosed on clinical parameters. 18 (45%) patients recovered kidney function after AKI. No differences were observed between patients with and without kidney function recovery, although patients without recovery had a numerical, but not statistically significant, higher mortality. Patients with biopsy-confirmed ICPi-induced AKI had an increased risk of mortality, as compared with the rest of the population-HR 1.83, 95% CI 1.22-2.74, p = 0.003. CONCLUSION: Use of nephrotoxic drugs and the location of malignancy appear to be common drivers of AKI in patients receiving ICPis for solid organ malignancy. Whether nephrotoxic agents or urinary tract obstruction may favor ICPi-related autoimmunity should be further studied.
