#2078 Study of spectrum of renal dysfunction in cancer patients on ICPI as mono or combination with conventional chemo in north India

Abstract

Abstract Background and Aims Although use of ICPI's have revolutionized the treatment of cancer patient with significantly improving the longevity of these patients but it also is associated with various adverse reactions known as iRAE's related to its use, which in due course is being revealed gradually. Kidney related iRAE's are important and also limitation to therapy, which could be a detrimental factor for these patients availing the beneficial effects of these revolutionary medications. Previous literature on these therapeutics had the limitations of being retrospective, small case series and case reports and evaluating only one or two parameters of kidney dysfunction, also the criteria used for evaluations had the limitation of standardization. With this we aimed to study the spectrum of renal dysfunction in cancer patients, receiving ICPI with or without conventional chemotherapy using standard criteria. Method Study involved patients with malignancy who had received at least 1 dose of ICPI as mono or combination with conventional chemotherapy. The primary end-point was 6 month assess the clinical spectrum & outcome of renal dysfunction, and the secondary end-points were the patient-level risk factors for renal dysfunction, the impact of renal dysfunction on clinical outcomes. Results Conducted through October 2021-2022, enrolled N = 156 (66 male & 90 females) & followed up for 6 months. 109 (69.9%) subjects developed KDIGO–AKI—Stage I (51.4%) & Stage II (35.8%) & non required RRT. The median duration for onset of AKI was 131 days. Proteinuria was observed in n = 143 (91.67%). n = 116 (74.3%) developed new-onset proteinuria. n = 40 (25.6%) were proteinuric at the start of the study & 27/40 (67.5%) were observed to have >50% increase in proteinuria, qualifying for proteinuria with therapy. 92/143 proteinuric subjects (64.3%) developed >1 g/day proteinuria. On subcategorizing proteinuria it was observed that 82/92 (57.3%) had 1–3 g/day proteinuria and ≥3.0 g/day proteinuria was observed in 10/92 (7.0%). Definitive ICPI–AKI could be attributed to only 2 subjects, as they underwent kidney biopsy for their kidney dysfunction and significant proteinuria. Secondary amyloid deposits in the glomeruli and mesangium was found in 1 subject & the other subject showed acute tubulointerstitial deposits with granular cast. Proteinuria and kidney dysfunction resolved with stoppage of the ICPI and steroids administration, which was consistent with the limited literature available for the management of ICPI related amyloidosis & iRAE. n = 88 had partial recovery of kidney dysfunction following an AKI event & complete recovery was seen in n = 3 (2.7%). >50% recovery in eGFR was observed in n = 41 (37.6%). Electrolyte abnormality commonly observed were hyponatremia, hypokalemia & hypomagnesemia & was seen in distributed almost equally, followed by hypocalcemia. Hypernatremia, hyperkalemia, hypermagnesemia & hypercalcemia were less commonly reported. Lastly mortality was also observed in n = 16 (10.2%), but could not be directly attributed to ICPI use, kidney dysfunction, malignancy type, comorbid conditions & other concomitants medication use. Conclusion To conclude this present prospective cohort study is a comprehensive assessment of the spectrum of renal dysfunction in cancer patients, among recipients of ICPI with or without conventional chemotherapy using standard criteria to the best of our knowledge, which has been the limitation of previous literature. We have shown a vast spectrum of kidney dysfunction possibly attributed to the ICPI's in malignancy patients. Viewed in respect to better QoL with ICPI therapy in malignancy patients, kidney related iRAE's could limit the patients from their beneficial effects. A possible persistent immune injury might have led to partial recovery of kidney dysfunction in majority. An unusual finding of secondary amyloid deposits with pembrolizumab, which possible might have occurred due to persistence of high levels of inflammatory markers due to these drugs. Thus underscoring the need for a close follow-up and recommend kidney biopsy to better & definitively identify the glomerular pathology & treatment accordingly.