C070 | REAL-LIFE STRATEGIES FOR THE INTEGRATED MANAGEMENT OF CHRONIC MYELOID LEUKEMIA AND SECOND PRIMARY MALIGNANCIES IN THE ERA OF MODERN THERAPIES

Introduction. BCR-ABL1 TKIs have transformed CML into a chronic, manageable disease; however, longer survival may expose patients to a higher risk of second primary malignancies, raising concern and complicating concurrent CML and cancer therapies. Aim. To characterize real-world management strategies, TKI modifications, and survival outcomes in CML patients developing an SPM in the era of modern therapies. Methods. We retrospectively reviewed 46 cases of CML complicated by a second primary malignancy (SPM) within an 820-patient cohort from several centers. De-identified datasets included age at CML, initial TKI choice, treatment line when the SPM occurred, molecular response depth, SPM pathology and stage, SPM treatment modalities, any variations in TKI therapy, and follow-up outcomes. Results. The median age at CML diagnosis was 64 years (range, 27–81). First‐line therapy consisted of imatinib in 87.2% of patients, nilotinib in 10.6%, and interferon in 2.1%. SPMs developed most often during imatinib treatment (69.6%), followed by nilotinib (15.2%), dasatinib (13.0%), and bosutinib (2.2%), after a median latency of 90 months (range, 10–277). At SPM onset, 65.8% of patients were in deep molecular remission. Predominant SPM types were genitourinary (30.4%), gastrointestinal (21.7%), respiratory (13.0%), and hematologic (13.0%) [Table 1]; 58.7% presented at an advanced stage. SPM treatments included chemotherapy (34.1%), combination regimens (17.1%), targeted agents (17.1%), radiotherapy (7.3%), surgery (7.3%), palliative care (7.3%), and others (9.8%). Half the cohort was already on reduced TKI doses at SPM onset; further reductions occurred in 6.5% (toxicity) and 15.2% (drug interactions) of cases. TKI switches (6.5%) and discontinuations (17.4%, mainly for poor SPM prognosis) were recorded, and 28.3% of patients attempted a treatment-free remission. Although loss of MR3 occurred in 11.6% of cases, no progressions to blast crisis or CML-related deaths were observed. Median OS was 188 months from CML diagnosis and 41 months from SPM diagnosis. Conclusions. Sustained deep molecular responses enable flexible TKI management to accommodate SPM therapies. Nonetheless, the prognosis and treatment burden of SPMs, combined with polypharmacy, predominantly influence TKI strategy and survival. These findings underscore the need for proactive, multidisciplinary monitoring and personalized therapeutic approaches.