CME / ABIM MOC / CE An Expert Discussion of Key New Data in CLL and MCL: How May It Impact Future Practice? Authors: Paolo Ghia, MD, PhD; Kami Maddocks, MD

https://www.medscape.org/viewarticle/expert-discussion-key-new-data-cll-and-mcl-how-may-it-impact-2025a1000pm5?page=1&sso=true&uac=148436CN&src=mkmcmr_reeng_recap_mscpedu_activity An Expert Discussion of Key New Data in CLL and MCL: How May It Impact Future Practice? Below are some key learning points to help reinforce the impact of this activity. ☑ CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) TRIALS: • GAIA/CLL13: The triplet ibrutinib-venetoclax-obinutuzumab showed superior progression-free survival (PFS) vs doublets and chemoimmunotherapy, but increased toxicity limits its use in all patient populations. • CAPTIVATE: Fixed-duration ibrutinib + venetoclax (15 months, median PFS not reached) achieved 66% PFS at 5.5 years, with successful retreatment possible. Ibrutinib + venetoclax achieved undetectable minimal residual disease (uMRD) in 60% of patients at end of therapy (EOT), which is a strong predictor for long-term PFS. • FLAIR: MRD-guided ibrutinib plus venetoclax outperformed continuous ibrutinib and fludarabine-cyclophosphamide-rituximab (FCR), with 73% of patients able to stop treatment by 60 months based on undetectable MRD achievement. • BRUIN CLL-321: Pirtobrutinib showed superior PFS (14 months) vs physician's choice of idelalisib + rituximab or bendamustine + rituximab in covalent Bruton tyrosine kinase (cBTK) inhibitor-exposed patients. In patient-reported outcomes, pirtobrutinib also demonstrated a clinically meaningful improvement at all visits in CLL/small lymphocytic lymphoma (SLL)-related symptoms, physical function, and fatigue. • CaDAnCe-101: The BTK degrader BGB-16673 was safe and well tolerated and achieved a 93.8% response rate in heavily pretreated patients (94% prior cBTK inhibitor exposed), representing a promising new drug class for relapsed/refractory (R/R) CLL/SLL. • Sonrotoclax + zanubrutinib: This next-generation B-cell lymphoma-2 (BCL-2)-BTK combination achieved 100% overall response rates and 48% complete response (CR)/CR with incomplete hematologic recovery (CRi) rates at 320 mg and a 30-month PFS of 95% in R/R CLL/SLL. ☑ MANTLE CELL LYMPHOMA (MCL) TRIALS: • ECHO: Adding acalabrutinib to bendamustine-rituximab significantly improved PFS in high-risk patients with MCL, particularly those with TP53 mutations, high Ki-67, and blastoid histology. • SYMPATICO: First-line ibrutinib + venetoclax for 2 years followed by ibrutinib maintenance showed durable responses in older patients and those with and without TP53 mutations, with PFS approaching 2 years in patients with TP53 mutation. • Mosunetuzumab + polatuzumab: This CD20 bispecific plus antibody-drug conjugate (ADC) combination achieved ~90% response rates, with ~80% CR in BTK inhibitor-exposed patients with MCL, with manageable grade 1 to 2 cytokine release syndrome (CRS). • VALOR: The chemo-free triplet rituximab + venetoclax + lenalidomide showed a 70% 5-year PFS in frontline MCL; this included high-risk disease, but patients with TP53 mutation had poor outcomes. • GoldiLox: Glofitamab + pirtobrutinib achieved ~80% response rates in BTK inhibitor-exposed patients with MCL, with enhanced steroid prophylaxis improving tolerability. • Sonrotoclax + zanubrutinib MCL: This combination achieved ~80% response rates, with a 70% CR rate and 84% 24-month duration of response in patients with R/R MCL.