Mazyar Shadman, MD, MPH

Panelists discuss how the anticipated FDA approval of acalabrutinib plus venetoclax as an all-oral fixed-duration regimen will expand frontline chronic lymphocytic leukemia (CLL) treatment options and shift practice patterns, with many patients preferring oral therapy over intravenous options, while acknowledging that the MAGIC trial comparing this combination with venetoclax-obinutuzumab may provide definitive efficacy data and that minimal residual disease (MRD)–guided approaches could further personalize treatment duration based on individual response assessment.

Panelists discuss how minimal residual disease (MRD)–directed strategies are evolving in frontline chronic lymphocytic leukemia (CLL) treatment, highlighting the FLARE study’s demonstration of overall survival benefit with fixed-duration ibrutinib-venetoclax compared with continuous ibrutinib, and emphasize that time to next treatment is a clinically meaningful end point because patients often don’t require immediate retreatment upon disease progression, providing valuable counseling information about treatment-free intervals for patients considering fixed-duration approaches.

Panelists discuss how Bruton tyrosine kinase (BTK) inhibitor selection requires careful consideration of patient-specific safety factors including cardiac comorbidities, renal function, infection risk, concurrent medications, and overall comorbidity index scores, emphasizing the importance of tailoring therapy based on individual patient profiles and preferences while recognizing that geriatric patients with chronic lymphocytic leukemia (CLL) often have multiple medical conditions that influence treatment tolerability and logistics.

Panelists discuss how long-term follow-up data from SEQUOIA Arm C demonstrates that zanubrutinib provides excellent outcomes for high-risk patients with TP53-disrupted chronic lymphocytic leukemia (CLL) with 72% progression-free survival at 5 years and increasing complete response rates over time (now around 20%), establishing it as a benchmark for continuous Bruton tyrosine kinase (BTK) inhibitor therapy in this population, while noting that deeper responses than historically expected may lead to future consideration of minimal residual disease–guided treatment discontinuation strategies.

Panelists discuss how treatment selection between continuous Bruton tyrosine kinase (BTK) inhibitor therapy and fixed-duration regimens involves shared decision-making that weighs patient preferences for time investment, with continuous therapy requiring ongoing visits but offering potentially superior efficacy for high-risk patients, while acknowledging that indirect comparisons like the MAIC analysis comparing zanubrutinib-venetoclax with acalabrutinib-venetoclax provide additional evidence despite methodological limitations when head-to-head trials are not feasible.

Panelists discuss how oral fixed-duration Bruton tyrosine kinase (BTK) inhibitor–venetoclax doublets may be considered for patients with high-risk TP53-disrupted chronic lymphocytic leukemia (CLL) based on promising phase 2 data showing high undetectable minimal residual disease (MRD) rates, but express concerns about infection risks with triplet regimens and emphasize the need for longer follow-up data to determine durability of remissions, with some preferring MRD-guided longer duration approaches over standard 14-cycle regimens for these highest-risk patients.

Panelists discuss how determining the optimal duration for fixed-duration chronic lymphocytic leukemia (CLL) therapies requires balancing factors like disease burden, patient age, and IGHV mutation status, with current standard approaches being 12 cycles for venetoclax-obinutuzumab or 14 cycles for oral Bruton tyrosine kinase inhibitor–venetoclax combinations, while recognizing that patients with unmutated IGHV may need longer treatment despite having excellent outcomes even without achieving undetectable minimal residual disease.

Panelists discuss how the SEQUOIA Arm D study demonstrates that zanubrutinib plus venetoclax provides an effective all-oral doublet option for treatment-naive patients with chronic lymphocytic leukemia (CLL) including those with high-risk TP53 abnormalities, achieving 60% undetectable minimal residual disease rates regardless of TP53 status, although high-risk patients may require longer treatment duration than the standard 1-year fixed approach to reach optimal disease clearance.

Panelists discuss how first-line chronic lymphocytic leukemia (CLL) therapy selection balances prognostic testing results with individual patient factors, weighing continuous Bruton tyrosine kinase (BTK) inhibitor therapy vs fixed-duration venetoclax-based regimens based on patient preferences for pill vs infusion treatment, comorbidities like cardiac issues, and the emerging role of oral BTK inhibitor–venetoclax doublets for appropriate candidates.

Panelists discuss how proper baseline testing, including cytogenetics, TP53 mutation status, and IGHV mutation testing, is essential for risk stratification and treatment selection in patients with chronic lymphocytic leukemia (CLL), with TP53 disruption being the most critical prognostic factor that typically directs clinicians toward continuous Bruton tyrosine kinase (BTK) inhibitor therapy.

Mazyar Shadman, MD, MPH, discusses data from arm D of the phase 3 SEQUOIA trial of zanubrutinib plus venetoclax in treatment-naive CLL/SLL.

Mazyar Shadman, MD, MPH, presents data from a matching adjusted indirect comparison (MAIC) of the efficacy of zanubrutinib versus acalabrutinib in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) based on data from the Phase 3 ALPINE and Phase 3 ASCEND trials.

Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center, presents updated SEQUOIA Arm D results demonstrating deep, durable responses and favorable safety with fixed-duration zanubrutinib plus venetoclax in treatment-naive CLL/SLL, including patients with del(17p)/TP53 mutations.

Mazyar Shadman, MD, MPH, presents a network meta-analysis evaluating Bruton tyrosine kinase (BTK) inhibitors in high-risk relapsed/refractory CLL, showing that zanubrutinib demonstrated the greatest efficacy in reducing progression and death compared with other BTK inhibitors and treatments.

Mazyar Shadman, MD, MPH, discusses the rationale and methodological framework of a network meta analysis of BTK inhibitors in relapsed/refractory CLL.

Mazyar Shadman, MD, MPH, discusses the rationale and methodological framework of a network meta-analysis aimed at evaluating the comparative efficacy of BTK inhibitors in R/R CLL.

Mazyar Shadman, MD, MPH, discusses the need for a clinical consensus in selecting optimal treatment strategies in diffuse large B-cell lymphoma.

Dr Shadman discusses key findings and implications from trials that were presented at the 2024 ASH Annual Meeting investigating zanubrutinib in CLL.

Dr. Mazyar Shadman presents an OncLive Rapid Readout on the SEQUOIA study, highlighting 5-year follow-up data that confirm zanubrutinib’s sustained progression-free survival superiority over bendamustine plus rituximab in treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma, with consistent efficacy across risk groups and a favorable long-term safety profile.

Mazyar Shadman, MD, MPH, discusses real-world outcomes following early dose adjustments of first-line ibrutinib in CLL/SLL.

Mazyar Shadman, MD, MPH, discusses the investigation of sonrotoclax in the CELESTIAL-TNCLL trial in treatment-naïve chronic lymphocytic leukemia.

Marc S. Hoffmann, MD, and Mazyar Shadman, MD, MPH, discuss ongoing trials and future treatment directions for chronic lymphocytic leukemia.

Marc S. Hoffmann, MD, and Mazyar Shadman, MD, MPH, discuss real-world safety data for BTK inhibitors in chronic lymphocytic leukemia from EHA 2024.

Marc S. Hoffmann, MD, and Mazyar Shadman, MD, MPH, discuss matching-adjusted indirect comparisons of BTK inhibitors in chronic lymphocytic leukemia.

Marc S. Hoffmann, MD, and Mazyar Shadman, MD, MPH, discuss findings from the SEQUOIA trial of zanubrutinib in treatment-naive chronic lymphocytic leukemia.

Marc S. Hoffmann, MD, and Mazyar Shadman, MD, MPH, discuss how to use data for BTK inhibitors to inform clinical decisions in chronic lymphocytic leukemia.

Marc S. Hoffmann, MD, and Mazyar Shadman, MD, MPH, on factors for selecting a BTK inhibitor or a venetoclax-based regimen in chronic lymphocytic leukemia.

Mazyar Shadman, MD, MPH, discusses the rationale for combining sonrotoclax plus zanubrutinib for treatment-naive chronic lymphocytic leukemia.

This is an evaluation of the results of a network meta-analysis covering the comparative efficacy of bruton tyrosine kinase Inhibitors in relapse/refractory chronic lymphocytic leukemia.

Mazyar Shadman, MD, MPH, discusses results from a network meta-analysis on the comparative efficacy of BTK inhibitors in relapsed/refractory CLL.