: Before targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL) defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK) had poorer prognosis with chemoimmunotherapy. Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts. A total of 808 patients were included (TN cohort, n = 320; R/R cohort, n = 488). Median follow-up was 59.1 months (TN cohort) and 44.3 months (R/R cohort); 51.3% and 26.8% of TN and R/R patients, respectively, remained on treatment at last follow-up. In the del(17p)/TP53m, uIGHV, and CK subgroups in the TN cohort, median progression-free survival (PFS) and median overall survival (OS) were not reached (NR). In the del(17p)/TP53m, uIGHV, and CK subgroups in the R/R cohort, median PFS was 38.6 months, 46.9 months, and 38.6 months, respectively and median OS was 60.6 months, NR, and NR, respectively. The safety profile of acalabrutinib-based therapy in this population was consistent with the known safety profile of acalabrutinib in a broad CLL population. Our analysis demonstrates long-term benefit of acalabrutinib-based regimens in patients with higher-risk CLL, regardless of line of therapy.

Acalabrutinib-based regimens in frontline or relapsed/refractory higher-risk CLL: Pooled analysis of 5 clinical trials / Davids, Matthew S; Sharman, Jeff P; Ghia, Paolo; Woyach, Jennifer A; Eyre, Toby A; Jurczak, Wojciech; Siddiqi, Tanya; Palhares de Miranda, Paulo A; Shahkarami, Mina; Butturini, Anna Maria; Emeribe, Ugochinyere; Byrd, John C. - In: BLOOD ADVANCES. - ISSN 2473-9529. - 8:13(2024). [10.1182/bloodadvances.2023011307]

Acalabrutinib-based regimens in frontline or relapsed/refractory higher-risk CLL: Pooled analysis of 5 clinical trials

Ghia, Paolo;
2024-01-01

Abstract

: Before targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL) defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK) had poorer prognosis with chemoimmunotherapy. Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts. A total of 808 patients were included (TN cohort, n = 320; R/R cohort, n = 488). Median follow-up was 59.1 months (TN cohort) and 44.3 months (R/R cohort); 51.3% and 26.8% of TN and R/R patients, respectively, remained on treatment at last follow-up. In the del(17p)/TP53m, uIGHV, and CK subgroups in the TN cohort, median progression-free survival (PFS) and median overall survival (OS) were not reached (NR). In the del(17p)/TP53m, uIGHV, and CK subgroups in the R/R cohort, median PFS was 38.6 months, 46.9 months, and 38.6 months, respectively and median OS was 60.6 months, NR, and NR, respectively. The safety profile of acalabrutinib-based therapy in this population was consistent with the known safety profile of acalabrutinib in a broad CLL population. Our analysis demonstrates long-term benefit of acalabrutinib-based regimens in patients with higher-risk CLL, regardless of line of therapy.
2024
Clinical Trials and Observations, Lymphoid Neoplasia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/159996
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