ROLE OF HAEMATOLOGY BIOMARKERS IN URINARY BLADDER AND RENAL CELL CANCER PATIENTS TREATED WITH IMMUNE-ONCOLOGICAL DRUGS

Background: Urinary bladder (UB) and Renal Cell Cancer (RCC) are common in men than women with poor outcome. The novel immunotherapy drugs like Immune Check Point Inhibitors (ICIs) are effective but expensive. However, a cost-effective and reliable biomarker to predict response and clinical outcomes is lacking. Objective: To study the association of pre-treatment haematological parameters with clinical outcome in urinary bladder and renal cell cancer patients treated with ICIs. Method: In a retrospective study, we included 52 patients with urinary bladder and RCC treated with ICIs from Jan 2008 to Dec 2019. Clinical evaluation and laboratory investigations were performed as a part of standard protocol. CBC parameters such as WBC, TLC, DLC, Hb, Platelet, Neutrophil:Lymplocyte Ratio(NLR), Platelet:Lymphocyte Ratio (PLR), Lymphocyte:Monocyte Ratio(LMR) were studied at the time of TMC enrolment(first) and before the start (pre-treatment) of the ICIs therapy(io). Results: Amongst the CBC parameters, WBC count, when categorized based on cut off from ROC at the time of TMC enrolment(first) and the pre-treatment of the ICIs therapy(io) were found to be significantly associated with progression of disease with p- value 0.012 with Hazard Ratio (HR) - 2.52 (95% C.I. - 1.2-5.31) & p- value 0.060 with Hazard Ratio (HR) – 1.99 (95% C.I. – 0.96-4.12) respectively. The ROC - based cut off for WBC at the time of TMC enrolment(first) and the pre-treatment of the ICIs therapy(io) were found to be 7.16 X10e3/µL (AUC of 72%) with 71% sensitivity and 72% specificity and 6.48 X10e3/µL (AUC of 74%) with 67% sensitivity and 72% specificity respectively to predict progressed cases with respect to non-progressed cases. Along with WBC, the pre-treatment Absolute Neutrophil Count (ANC) (>3.67)& Absolute Monocyte count (AMC)(>0.42) pre-treatment of the ICIs therapy(io)) showed a significance with Hazard Ratio (HR) – 3.09(95% C.I.– 1.26-7.6) with p-value 0.010, Hazard Ratio (HR) – 3.48(95% C.I. - 1.6-7.57)and p-value <0.001 respectively. The ROC- based cut off for ANC at the pre-treatment of the ICIs therapy(io) were found to be 3.67 X10e3/µL (AUC of 68.4%) with 82.4% sensitivity and 50% specificity. Similarly The ROC- based cut off for AEC at the time of TMC enrolment(first) and AMC at the pre- treatment of the ICIs therapy(io) were found to be 0.22 X10e3/µL (AUC of 69.6%) with 55.9% sensitivity and 82.3% specificity and 0.42 X10e3/µL (AUC of 74.7%) with 72.7% sensitivity and 72.2% specificity respectively to predict progressed cases compared to non-progressed cases. Of 52 patients, 34 (65.4%) had progression. The median (m) PFS was 8.67 months (95% CI 2.26 - 15.09).The one year PFS rate was 46.5 (95% CI 31.2 -60.5). The mPFS in WBC <=7.16 was 26.48 months (95% CI 0 - 53.08) higher than the mPFS of 5.75 (95% CI 0.21 - 11.29) in WBC >7.16 with P value 0.012 at the time of TMC enrolment. Similarly, the mPFS in WBC pre- treatment of the ICIs therapy(io))<=6.48 was13.11 months (95% CI 0 – 28.95) higher than the mPFS of 6.18 (95% CI 2.67-9.68) in WBC >6.48 with P value 0.060.Along with WBC, the mPFS in ANC at the pre- treatment of the ICIs therapy(io)<=3.67 was 27.4(95% CI 0-55.21) higher than the mPFS of 6.18(95% CI 1.47-10.88)in ANC >3.67 with p value 0.010. The mPFS in AMC at the pre-treatment of the ICIs therapy(io)< =0.415 was 27.4 (95% CI 9.41-45.39) higher than the mPFS of 3.91 (95% CI 0.06-7.76) in AMC >0.415with p- value <0.001.We observed mPFS in immunotherapy cycles >=6 to be 15.9 (95% CI 6.98-24.82) was higher than the mPFS of 2.23 (95% CI 0.99-3.481) in immunotherapy cycles<6 with p value 0.025. The patients were followed for a period of 40.35 months (95% CI 26.98 - 53.71). Of 52 patients, 32(61.5%) patients deceased with median OS of 18.46 months (95% CI 10.12 - 26.80) and the one year OS rate was 57.6 (95% CI 41.6 - 70.6). Conclusion: Simple, routinely available and cost effective WBC (TLC), Absolute Neutrophil Count (ANC) ,Absolute Monocyte Count (AMC) and Absolute Eosinophil Count (AEC) from CBC test has a great potential to be used as a biomarker to predict response and clinical outcomes in patients with urinary bladder cancer and RCC patients treated with ICIs.