Real-world understanding of the unmet need for treatment of non-covalent BTKi in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Abstract

e19028 Background: Non-covalent (nc) Bruton Tyrosine Kinase inhibitors (BTKi) for the treatment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL) provide patients with a new treatment option after resistance to on-target BTK mutations or PLCγ2 mutations that bypass BTK inhibition. Given the December 1, 2023 accelerated FDA approval for pirtobrutinib, a nc-BTKi, in the treatment of CLL/SLL for treatment of patients who have received at least two prior lines of therapy with a covalent (c) BTKi and a B-Cell Lymphoma 2 Protein Inhibitor (BCL2i), we sought to understand the addressable population for treatment with nc-BTKI therapy in a real-world database of CLL/SLL patients. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify CLL/SLL pts for the analysis. The CLL patients included for the analysis were on a treatment in 2023 and must have had either >5 CLL/SLL diagnosed visits or more CLL/SLL visits than non-CLL/SLL visits if <5 CLL/SLL diagnosed visits. Descriptive analyses were used for this study. Results: Of the 6,992 patients treated for CLL/SLL in 2023, the median age at treatment start was 71, 62% were male, 65% identified as White, 6% as African American, and 29% as Other. Of the pts, 12% received a c-BTKi and BCL2i, 64% received a c-BTKi only, and 12% received a BCL2i only. Of the 12% of pts who received a c-BTKi and BCL2i, 191 pts started a subsequent line of therapy. Among pts who received a c-BTKi and BCL2i, 79% received a BTKi therapy first, 10% received a BCL2i therapy first, and 12% had a line of therapy with both a BTKi and BCL2i. We found 59 pts who received nc-BTKi; among those pts, 51% received a c-BTKi and BCL2i prior to initiation of nc-BTKi. The median age at first treatment for CLL/SLL was 71.7 for those who received a c-BTKi, 71.1 for those who received a BCL2i, and 70.8 for those who received nc-BTKi. The median age at first diagnosis for CLL/SLL was 68 for those who received a c-BTKi, 66 for those who received a BCL2i, and 63 for those who received nc-BTKi. The median time to first treatment was 470 days for pts treated with a c-BTKi, 507 days for pts treated with BCL2i, and 587 days for pts treated with nc-BTKi. Conclusions: We found that among nearly 7,000 treated patients in the database, 12% were treated with both a c-BTKi and BCL2i; of those, just 23% started a subsequent treatment. Among patients who were treated with a nc-BTKi we found their median age at treatment start and diagnosis was lower than those who received a c-BTKi or BCL2i respectively.