Patients with aggressive hematological malignancies and second primary malignancies can develop in those with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). There needed to be more research on the actual incidence of second hematological malignancies (SHM) in the era of targeted therapy, resulting from a major change in the therapeutic landscape for CLL/SLL. To estimate the incidence of SHM in CLL/SLL patients, data from the Surveillance, Epidemiology, and End Results (SEER) database were examined.

To find adult patients with an initial CLL/SLL diagnosis and a subsequent SHM diagnosis (>2 months after the first diagnosis), they searched the SEER 17 registry. The International Classification of Disease code for Oncology (ICD-O-3) was used to identify codes assigned to CLL/SLL (9,823/3) and 11 types of SHM [9,650/3: Classical Hodgkin lymphoma (HL), 9,673/3: Mantle cell lymphoma (MCL), 9,680/3: Diffuse large B-cell lymphoma (DLBCL), 9,687/3: Burkitt lymphoma (BL), 9,689/3: Splenic marginal zone lymphoma (SMZL), Acute lymphoblastic leukemia/lymphoma (ALL: consisting of 9,811/3: B lymphoblastic leukemia/lymphoma, 9,728/3: Precursor B-lymphoblastic lymphoma, 9,836/3: Precursor B-cell lymphoblastic leukemia and 9837/3: T lymphoblastic leukemia/lymphoma), 9,833/3: B-cell prolymphocytic leukemia(B-PLL), 9,834/3: T-cell prolymphocytic leukemia(T-PLL), 9,861/3: Acute myeloid leukemia (AML), 9,863/3: Chronic myeloid leukemia (CML), 9,989/3: Myelodysplastic syndrome (MDS)]. They defined SHM as any blood cancer diagnosed following either treated or untreated CLL/SLL. Patients with CLL/SLL who had an uncertain survival time or another hematological malignancy at the diagnosis were excluded. Estimates of survival time (in months) and vital status were made using data that ended in December 2019 as the cut-off date (dead or alive). Using SEER Stat v software, additional information, including demographics and treatment specifics, was retrieved. The median follow-up period was calculated using the reverse Kaplan Meier technique. To determine the difference between categorical variables, the Chi-squared test was performed. To calculate overall survival (OS), the Kaplan Meier technique and the log-rank test were utilized.

About 1,390 out of 78,943 adult CLL/SLL patients, or 1.8%, experienced SHM during the research period. In about 1,255 patients passed the qualifying requirements (129 patients had a gap of <2 months between their index diagnosis and SHM diagnosis, 3 CLL/SLL patients had an unclear survival length, and 3 patients had concurrent diagnoses of another hematological malignancy). Around 90% (1,130) of the 1,255 patients were White, and 63.7% (799) were male. When CLL/SLL and SHM were first diagnosed, the median ages were 65 and 70, respectively. The most frequently reported SHMs were DLBCL (57.2% [n=718]), MCL (10.8% [n=136]), and MDS (8.69% [n=109]). Following the diagnosis of CLL/SLL and SHM, the median (95% CI) follow-up time was 153 (145.0-160.9) and 58 (53.4-62.6) months, respectively. Gender and SHM were not significantly associated (P =0.146). Chemotherapy (CT) was administered to 394 (31.4%) patients with CLL/SLL, whereas 861 (68.6%) patients either did not receive treatment or had their status unclear. OS was 12 (95%CI 10.1-13.9) months after any SHM diagnosis. AML had the lowest OS (3(1.3-4.6)) while SMZL had the greatest OS (113(82.7-143.3)). When compared to patients who received chemotherapy for CLL/SLL, patients who did not receive chemotherapy (for CLL) or whose treatment details were unknown had longer survival times after receiving a SHM diagnosis (median survival months (95%CI): 13(10-16) vs. 10(8-12), P =0.034; hazard ratio = 1.159 (95%CI: 1.007-1.334).

About 2% of CLL/SLL patients had SHM, which was most frequently seen in males and people of white ethnicity. After an SHM diagnosis, the average survival time was around a year. Strong measures for SHM surveillance were required given the improvement in overall survival brought about by more targeted therapy for CLL/SLL.