Can immune therapy prevent pre-clinical cancer from progression? The impact of immune therapy on secondary cancer incidence.
Authors: Adcock Bridget , Batah Heya , Lee Monica , Patel Preeyal , Patel Meera , Zureigat Hadil , Hassan Ahmed , Nurse Daniel Paul , Rauf Asad , Tomer Jacqulyn , Ingraham Austin , Hoen Douglas Robert , Zabor Emily Craig , Mustafa Ali Moaath Khader 
Published: June 2024

2651 Background: 40% of people will develop cancer (Ca) in their lifetime, and 18% of those will develop secondary (2ry) Ca. Currently, there are no known therapeutic interventions to prevent Ca. Immune therapy (IT) revolutionized Ca care and increased survival in many Ca types. Because IT increases immune surveillance, it might halt pre-clinical Ca from progression into clinical disease. We hypothesize that IT acts to prevent or delay the development of 2ry Ca in those treated with IT for primary (1ry) Ca. Methods: We conducted a retrospective cohort study on Ca patients (pts) ≥ 18 years & treated between 2010-2022 at Cleveland Clinic, Ohio. We included Ca diagnoses where IT was utilized in first line therapy, per 2022 NCCN guidelines. We excluded pts who were not treated or whose 1ry therapy was not determined. 2ry Ca was defined with strict criteria and excluded recurrent 1ry Ca. We collected the following data: 1ry Ca and stage, 2ry Ca type and incidence, type of first & subsequent line therapy, comorbidities, smoking & alcohol use. Molecular data and PD-1/PDL-1 are currently being collected. The comparison groups were pts who received IT +/- Chemotherapy (CTX) +/- radiation (RT) (IT-G) vs. pts who received CTX or targeted therapy +/- RT (Non-IT). IT included anti-(PD-1, PD-L1, LAG-3, CTLA4: 99.9% of cases) or others (IL-2, IL-12, IL-15, Inf α: 0.1%). Outcome was 2ry Ca-free survival. Multivariable regression was used to account for confounding. Results: The initial sample size was 19,253 pts, and 6,376 met the criteria. There was 10.2% bladder stage II-IV, 2.5% endometrial stage IV, 21.7% esophagus/gastric stage II-IV, 13% head/neck stage IV, 4.9% clear cell renal stage III/IV, 0.7% BRAF mutated melanoma stage IV, 28.2% lung adenoCa stage IIIb/IV, 9.1% squamous cell lung Ca stage IIIb/IV, and 10% small cell lung Ca stage IIIb/ IV. Baseline characteristics of comparison groups are presented in table below. 1,173 (18%) received first line and 1,023 (16%) received subsequent line IT. With a median follow up of 12.2 months for whole population, 319 2ry Ca were diagnosed. The two-year 2ry Ca free survival was 98% (CI: 97-99) in pts who received first line IT, compared to 93% (93-94) in pts who did not get first line IT. On multivariable regression, pts who received IT at any time compared to pts who received non-IT had a 77% decrease in 2ry Ca incidence (Hazard ratio: 0.33, 95CI 0.22-0.50, P<0.001). Conclusions: Our study concludes that incidence of 2ry Ca in pts treated with IT was lower than pts who received non-IT. In this proof-of-concept study, we showed that IT may increase immune surveillance to prevent Ca in its pre-clinical stage. Future interventional studies are needed to explore if IT can be utilized in 1ry & 2ry prevention in high risk, Ca-free populations. [Table: see text]