Symposium | First-line BTK inhibitors in clinical practice: Case study clinic

During the Lymphoma Hub virtual symposium on October 23, 2024, entitled Customizing first-line Bruton‘s tyrosine kinase (BTK) for chronic lymphocytic leukemia (CLL), Francesc Bosch, Vall d'Hebron Barcelona Hospital Campus, Barcelona, ES, shared a clinical case report and discussed treatment optimization strategies with BTK inhibitors in first-line CLL.

Bosch began by presenting a clinical case of a 73-year-old fit male with a medical history of hypertension who developed asymptomatic CLL (Figure 1). Bosch discussed the treatment approach, including key diagnostic steps such as imaging assessment, and the impact of various factors such as age, fitness, mutational status, and international prognostic index score, when selecting a treatment option. He also considered the latest data from clinical trials of BTK inhibitors in first-line CLL by highlighting long-term outcomes from the CAPTIVATE (Figure 2), GLOW, ELEVATE-TN, RESONATE-2, SEQUOIA, CLL13, and CLL14 trials, and described the deep and durable responses found with BTK inhibitors, particularly in patients with high-risk features including unmutated IGHV and del(17p)/TP53^mut.

Figure 1. Clinical case of a 73-year-old male with CLL  

B2m, β2 microglobulin; BCM, below costal margin; CLL, chronic lymphocytic leukemia; FISH, fluorescence in situ hybridization; Hb, hemoglobin; LDH, lactate dehydrogenase; LN, lymph node; uIGHV, unmutated IGHV; W&W, watch and wait.

Figure 2. Key outcomes from the CAPTIVATE trial in high-risk CLL: FD + MRD cohorts*  

BM, bone marrow; FD, fixed-duration; CR, complete response; CRi, complete response with incomplete BM recovery; IGHV, immunoglobulin heavy chain variable region; m, mutated; MRD, measurable residual disease; mut, mutation; nPR, nodular PR;  OR overall response; PB, peripheral blood; PFS, progression-free survival; PR, partial response; u, unmutated; uMRD, undetectable MRD.
*Data from Allan, et al. ¹ 

Key takeaways:

• TP53^mut and IGHV molecular status should be considered when selecting treatments for patients with CLL.
• Covalent BTK inhibitors demonstrate high efficacy in patients with unmutated IGHV.
• B-cell lymphoma-2 inhibitors and anti-CD20 combinations exhibit lower efficacy in patients with unmutated IGHV.
• Fixed-duration ibrutinib + venetoclax demonstrates efficacy in patients with high-risk CLL (with del(17p)/TP53^mut and/or unmutated IGHV), although longer follow-up is needed.

This independent educational activity was supported by an educational grant from Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC. All content was developed independently by SES in collaboration with the faculty. The funder was allowed no influence on the content of this activity.