Supplementary materials: Assessment of second primary malignancies among treated and untreated patients with chronic lymphocytic leukemia using real-world data from the USA

<b>These are peer-reviewed supplementary figures and tables for the article '</b><b>Assessment of second primary malignancies among treated and untreated patients with chronic lymphocytic leukemia using real-world data from the USA</b><b>' published in the</b><b> </b><b><i>Journal of Comparative Effectiveness Research</i></b><b>.</b><b>Supplementary Figure 1: </b>Timing of events for the treated and untreated subgroups<b>Supplementary Figure 2:</b> The covariate balance between the treated and untreated subgroups<b>Supplementary Table 1: </b>Procedure and NDC codes for CLL treatments<b>Supplementary Table 2: </b>Diagnosis codes for SPMs<b>Aim: </b>Improved management of chronic lymphocytic leukemia (CLL) has resulted in a growing population of CLL survivors; these patients have a higher risk of developing second primary malignancies (SPMs) versus the general population. This retrospective cohort study aims to assess the timing, frequency, incidence and types of SPMs in treated and untreated patients with CLL in the USA, using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links a nationally representative cancer registry with Medicare claims data. <b>Patients &amp; methods:</b> Patients aged ≥66 years with newly diagnosed CLL between 1 January 2010 and 31 December 2016, who were enrolled in Parts A and B of Medicare for ≥12 months pre-diagnosis of CLL were selected from the database. Patients were assessed for ≥36 months until the end of continuous enrollment in Medicare Parts A, B and D, a switch to a health maintenance organization, death, or end of the study period (December 2019). <b>Results:</b> Of 3053 patients included in the analyses, 620 (20.3%) were treated and 2433 (79.7%) were untreated within 36 months of diagnosis. Overall, 638 (20.9%) patients developed a SPM, 26.8% of patients in the treated cohort and 19.4% of patients in the untreated cohort. The most common SPMs for both cohorts were squamous cell carcinoma and acute myeloid leukemia. Among the 166 treated patients who developed a SPM, a greater proportion developed their first SPM after treatment initiation versus those who developed their first SPM prior to treatment initiation (p &lt; 0.001). A significantly lower percentage of patients who received targeted therapy developed a SPM (p &lt; 0.05) versus patients treated with anti-CD20 + chemotherapy. <b>Conclusion: </b>Findings indicate that treatment type and timing can affect SPM development in patients with CLL. Combined with previous findings, this can help inform best practices in monitoring for SPM in patients with CLL.

本数据集为发表于《Journal of Comparative Effectiveness Research》（《比较效果研究杂志》）的同行评议补充图表与表格，配套论文为《Assessment of second primary malignancies among treated and untreated patients with chronic lymphocytic leukemia using real-world data from the USA》（《基于美国真实世界数据评估慢性淋巴细胞白血病（chronic lymphocytic leukemia, CLL）接受治疗与未治疗患者的第二原发恶性肿瘤（second primary malignancies, SPM）风险》）。

补充图1：接受治疗与未治疗亚组的事件发生时序
补充图2：接受治疗与未治疗亚组的协变量平衡情况
补充表1：CLL治疗方案与国家药物代码（National Drug Code, NDC）
补充表2：SPM诊断代码

**研究目的**：慢性淋巴细胞白血病诊疗方案的优化使得CLL幸存者群体持续扩大，相较于普通人群，此类患者罹患第二原发恶性肿瘤的风险更高。本回顾性队列研究依托监测、流行病学与最终结果-联邦医疗保险数据库（Surveillance, Epidemiology, and End Results, SEER-Medicare）——该数据库将全国代表性癌症登记系统与联邦医疗保险理赔数据进行关联——旨在评估美国境内接受治疗与未治疗的CLL患者中，SPM的发生时序、发生频率、发病率及病理亚型。

**患者与研究方法**：本研究从数据库中筛选出2010年1月1日至2016年12月31日期间新确诊为CLL、且在确诊前已连续参加联邦医疗保险A、B计划至少12个月、年龄≥66岁的患者。研究随访时长至少36个月，随访终止条件包括：患者停止连续参保联邦医疗保险A、B、D计划、转为健康维护组织（Health Maintenance Organization, HMO）参保、患者死亡或研究周期结束（2019年12月）。

**研究结果**：本研究共纳入3053例患者进行分析，其中确诊后36个月内接受治疗者620例（占比20.3%），未接受治疗者2433例（占比79.7%）。整体而言，共计638例（20.9%）患者发生SPM，其中治疗队列占比26.8%，未治疗队列占比19.4%。两个队列最常见的SPM均为鳞状细胞癌与急性髓系白血病。在166例发生SPM的接受治疗患者中，治疗启动后出现首发性SPM的患者占比显著高于治疗前即出现首发性SPM的患者（p < 0.001）。相较于接受抗CD20单抗联合化疗的患者，接受靶向治疗的患者发生SPM的比例显著更低（p < 0.05）。

**研究结论**：本研究结果表明，治疗类型与治疗时序可影响CLL患者SPM的发生风险。结合既往研究成果，本发现可为CLL患者SPM监测的临床最佳实践提供参考依据。