Idelalisib for Treatment of Follicular Lymphoma and Chronic Lymphocytic Leukemia in Clinical Trials Versus the Real World: Treatment Duration and Survival Are Associated with Pretreatment Modified Charlson Score

Background: Idelalisib (IDEL) is a phosphatidylinositol-3 kinase (PI3K) inhibitor approved as a single agent for treatment of relapsed follicular lymphoma (FL) and in combination with rituximab for treatment of relapsed chronic lymphocytic lymphoma (CLL). The clinical trials supporting IDEL approval excluded patients with many comorbidities. We sought to investigate whether higher comorbidity burden among real world (RW) patients receiving IDEL might lead to differences in treatment duration, overall survival, or infection rates compared to clinical trial (CT) subjects. Methods: CT data from the sponsor and RW data from Medicare were obtained for patients aged ≥65 years receiving: 1) IDEL monotherapy for FL or 2) IDEL with rituximab (IDEL+R) for CLL. A pretreatment modified Charlson Score (mCS; Quan H, 2011) was calculated using medical records for CT subjects and diagnostic reimbursement codes for RW beneficiaries. Treatment duration for IDEL was calculated from treatment start until the last patient contact for CT subjects and until the final day supply for RW beneficiaries. Overall survival was obtained from intention to treat data for CT subjects and through linkage to Social Security for RW beneficiaries. Serious infections were coded as Grade ≥3, as a serious adverse event, or required intravenous antibiotics for CT subjects. For RW beneficiaries, serious infections were obtained through manual abstraction of hospital discharge diagnoses or coded with intravenous antibiotics in emergent care. Fatal infections were defined as serious infections within 30 days prior to death. Results are reported descriptively and using Cox Proportional Hazards Models, adjusted by age, gender, mCS, and US location. Statistical modeling was intended to describe the generalizability of CT results to unselected RW population. Results: A total of 26 CT subjects aged ≥65 years receiving IDEL monotherapy for FL from Study 101-09 were compared to 305 RW beneficiaries aged ≥65 years receiving IDEL for FL. A total of 89 CT subjects aged ≥65 years receiving IDEL+R for CLL in Study 312-116/117 were compared to 294 RW beneficiaries aged ≥65 years receiving IDEL+R for CLL. Key clinical comparisons are presented in the table below. Age and mCS•RW beneficiaries receiving IDEL for FL had more patients ≥75 years (54% vs 35%) and with a mCS >3 (52% vs 12%) than CT subjects.•RW beneficiaries receiving IDEL+R for CLL had more patients ≥75 years old (52% vs 36%) and with a mCS >3 (52% vs 2