Shuo Ma1, Rebecca J Chan2, Lin Gu3, Guan Xing3, Nishanthan Rajakumaraswamy4, Bianca B Ruzicka2, Nina D Wagner-Johnston5. 1. Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, IL. Electronic address: shuo-ma@northwestern.edu. 2. Medical Affairs, Gilead Sciences Inc., Foster City, CA. 3. Biostatistics, Gilead Sciences Inc., Foster City, CA. 4. Clinical Research, Gilead Sciences Inc., Foster City, CA. 5. Oncology-Hematologic Malignancies, Johns Hopkins University, Baltimore, MD.
Abstract
BACKGROUND: Idelalisib is a phosphatidylinositol 3-kinase δ inhibitor approved for relapsed/refractory follicular lymphoma, a type of indolent non-Hodgkin lymphoma (iNHL), and chronic lymphocytic leukemia (CLL). Idelalisib-triggered adverse events (AEs) may be managed with treatment interruption and/or dose reduction, potentially extending therapy duration and increasing the likelihood of continued response. PATIENTS AND METHODS: Post hoc analyses were conducted to evaluate clinical outcomes after AE-induced idelalisib interruption for 125 patients with iNHL and 283 with CLL. RESULTS: Progression-free survival (PFS) was longer for patients with iNHL who experienced ≥ 2 interruptions versus those with 0 interruptions who discontinued idelalisib or study because of AEs (hazard ratio 0.33; P = .0212). Both PFS and overall survival were longer for patients with CLL with ≥ 2 interruptions versus 0 interruptions in those who discontinued therapy because of an AE (hazard ratio PFS 0.50, overall survival 0.41; P < .005). Clinical benefits persisted for patients with CLL who experienced treatment interruption after receiving idelalisib for ≥ 6 months. Supplementing interruption with dose reduction did not worsen clinical outcomes. However, time off therapy of ≥ 8% may diminish the clinical benefit of treatment interruption. CONCLUSION: Idelalisib interruption and dose reduction were associated with enhanced clinical outcomes for patients with relapsed/refractory iNHL or CLL who experienced an AE, supporting this management strategy when indicated.
BACKGROUND: Idelalisib is a phosphatidylinositol 3-kinase δ inhibitor approved for relapsed/refractory follicular lymphoma, a type of indolent non-Hodgkin lymphoma (iNHL), and chronic lymphocytic leukemia (CLL). Idelalisib-triggered adverse events (AEs) may be managed with treatment interruption and/or dose reduction, potentially extending therapy duration and increasing the likelihood of continued response. PATIENTS AND METHODS: Post hoc analyses were conducted to evaluate clinical outcomes after AE-induced idelalisib interruption for 125 patients with iNHL and 283 with CLL. RESULTS: Progression-free survival (PFS) was longer for patients with iNHL who experienced ≥ 2 interruptions versus those with 0 interruptions who discontinued idelalisib or study because of AEs (hazard ratio 0.33; P = .0212). Both PFS and overall survival were longer for patients with CLL with ≥ 2 interruptions versus 0 interruptions in those who discontinued therapy because of an AE (hazard ratio PFS 0.50, overall survival 0.41; P < .005). Clinical benefits persisted for patients with CLL who experienced treatment interruption after receiving idelalisib for ≥ 6 months. Supplementing interruption with dose reduction did not worsen clinical outcomes. However, time off therapy of ≥ 8% may diminish the clinical benefit of treatment interruption. CONCLUSION: Idelalisib interruption and dose reduction were associated with enhanced clinical outcomes for patients with relapsed/refractory iNHL or CLL who experienced an AE, supporting this management strategy when indicated.
Authors: Bart Vanhaesebroeck; Matthew W D Perry; Jennifer R Brown; Fabrice André; Klaus Okkenhaug Journal: Nat Rev Drug Discov Date: 2021-06-14 Impact factor: 112.288
Authors: Nina D Wagner-Johnston; Jeff Sharman; Richard R Furman; Gilles Salles; Jennifer R Brown; Tadeusz Robak; Lin Gu; Guan Xing; Rebecca J Chan; Nishanthan Rajakumaraswamy; Ajay K Gopal Journal: Leuk Lymphoma Date: 2021-07-28