Outcomes of patients with concurrent Chronic Lymphocytic leukemia (CLL) and Non-small cell lung carcinoma (NSCLC)

CLL is the most common type of leukemia and NSCLC is the second most common cause of cancer but leading cause of cancer-related mortality in adults. Newer treatments have improved survival in both of them individually, but limited data is available on clinical and treatment outcomes of patients with concurrent CLL and NSCLC.

A single-center retrospective study all patients diagnosed with both CLL and NSCLC at Moffitt Cancer Center between 01/2001- 12/2023. The primary end points were estimated 5-year overall survival (OS) and progression-free survival (PFS) using the Kaplan–Meier method.

38 patients were identified, the majority being males (52.6%) and white (92.1%). In our cohort, most patients were smokers (73.7% past and 10.5% current) and had history of smoking >20 pack years (65.8%). The median age of diagnoses for CLL and NSCLC were 62 and 69.5 years, respectively.

For CLL, genomic abnormalities detected by fluorescence in situ hybridization included unmutated IGHV (39.5%), del13q (39.5%), del11q (21.1%), trisomy 12 (21.1%), del17p (5.3%). At diagnosis, the majority of patients were Rai and Binet stage 0 (54.5%) and around 42.1% patients required treatment. For NSCLC, various histologies detected includes adenocarcinoma (76.3%), squamous cell carcinoma (13.2%) and others (7.9%). Molecularly, 17 patients were found to have driver mutations by next generation sequencing, notably including TP53 (26.3%), KRAS (15.8%), EGFR (10.5%), BRAF (10.5%), ATM (10.5%) and ALK (10.5 %). At diagnosis, patients were most often diagnosed with clinical stage I (48.5%), T1 (65.6%), N0 (48.5%) and M0 (69.7%) disease. Most patients received systemic treatment (47.4%), some underwent surgery (28.9%) and radiation (7.9 %). Interestingly, 14 patients had a third malignancy, which included colorectal (5.3%), breast (10.5%), prostate (7.9%), renal cell carcinoma (2.6%), melanoma (5.3%), parotid acinar cell carcinoma (2.6%) and diffuse large B cell lymphoma (2.6%).

The estimated 5-year OS was 46% (95% CI 32- 66) and PFS was 44% (95% CI 30-64). On comparison, median OS and median PFS was higher in females as compared to males (121.8 vs 45.1 months and 52.6 vs 44.6 months respectively) and patients with history of smoking < 20 pack years as compared to >20 pack years (121.6 vs 52.6 months and 121.8 vs 41.8 months, respectively) but the results did not reach statistical significance.

Older age (> 60 years), male sex and smoking are common risk factors. Most patients with NSCLC were diagnosed as TP53 mutated adenocarcinomas whereas most CLL were IGHV unmutated and TP53 wildtype. Patients with concurrent CLL and NSCLC are at higher risk for development of third primary malignancies.