What were the key findings of the SEQUOIA study regarding zanubrutinib?

The SEQUOIA study demonstrated that zanubrutinib provides sustained efficacy in patients with CLL/SLL harboring del(17p) mutations. The 5-year follow-up data showed high progression-free survival (PFS) and overall response rates (ORR).

What are the common side effects associated with zanubrutinib treatment?

Common adverse effects of zanubrutinib include infections, bleeding, neutropenia, hypertension, anemia, thrombocytopenia, and atrial fibrillation/flutter. Most of these are manageable, but some may require medical intervention.

How does zanubrutinib compare to other treatments for CLL/SLL?

Zanubrutinib has shown superiority over ibrutinib in head-to-head trials,particularly in patients with high-risk disease such as del(17p) mutations. It offers a more selective and potent BTK inhibition, potentially leading to better outcomes.

What is the meaning of the del(17p) mutation in CLL/SLL?

The del(17p) mutation is a genetic abnormality associated with poorer prognosis in CLL/SLL patients. It indicates the deletion of a portion of chromosome 17, which includes the TP53 gene, a tumor suppressor. Zanubrutinib has proven effective in treating patients with this mutation.

What is the overall survival rate for CLL/SLL patients treated with zanubrutinib?

The estimated 60-month overall survival (OS) rate for patients treated with zanubrutinib is 85.1% (95% CI, 76.9%-90.6%), or 87.0% (95% CI,79.0%-92.1%) when adjusted for COVID-19, according to the SEQUOIA study.

lilly’s Pirtobrutinib Demonstrates Significant⁤ Progression-Free Survival Benefit in First-Line CLL/SLL Treatment

INDIANAPOLIS, IN⁢ – September 8, 2025 – Patients newly diagnosed with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) experienced a statistically significant improvement ‌in progression-free survival (PFS) when treated ⁣with pirtobrutinib, a first-in-class non-covalent Bruton’s tyrosine‍ kinase (BTK) inhibitor, ‌according ‌to results from the Phase 3 BRUIN CLL-313 trial.the⁤ findings bolster the potential⁢ of pirtobrutinib as a ⁢key treatment option‍ for individuals‌ with these blood‍ cancers, even⁣ before prior therapies have been administered.

Currently,treatment options for CLL/SLL are⁤ evolving,and this ⁢data offers a⁣ promising new avenue for⁣ patients. The BRUIN CLL-313 trial results, alongside those from the BRUIN CLL-314 trial, are expected to support a label expansion for pirtobrutinib, allowing its use earlier in the treatment pathway‌ -‌ including for those⁣ who haven’t received BTK inhibitor⁣ therapy previously.This is especially significant as pirtobrutinib’s unique mechanism of action, as a non-covalent BTK inhibitor, may overcome resistance observed with other BTK inhibitors.

while overall survival (OS) data ‍is still maturing, initial trends indicate ‌a favorable outcome for patients receiving pirtobrutinib, ‌with a primary OS analysis anticipated in 2026. ⁣The safety profile observed in the BRUIN CLL-313 trial remained consistent with previously reported studies.

“The results from BRUIN CLL-313 are striking and provocative, across both PFS and OS endpoints, further demonstrating the ‌potential of⁣ pirtobrutinib to be a meaningful treatment option ‍for peopel‌ with ⁤untreated CLL/SLL,” stated Jacob Van Naarden, executive vice president and president of Lilly Oncology. “With this third positive phase 3 study, we continue to build the clinical evidence supporting the possible role of pirtobrutinib in a variety ⁤of CLL/SLL treatment settings, including treatment-naïve, BTK inhibitor-naïve and BTK inhibitor exposed.”

Full study results will be presented at an upcoming medical congress and submitted for publication in a peer-reviewed ⁤journal.

Zanubrutinib Demonstrates Sustained Efficacy in CLL/SLL Patients with del(17p) Mutation

Q: What is zanubrutinib and how does it treat CLL/SLL?

Zanubrutinib (Brukinsa) is a Bruton tyrosine kinase (BTK) inhibitor used to treat chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It works by blocking the BTK enzyme, which is crucial for the survival and proliferation of CLL/SLL cells.

Table of Contents

Zanubrutinib Demonstrates Sustained Efficacy in CLL/SLL Patients with del(17p) Mutation

Five-year follow-up data from the SEQUOIA study reveals that zanubrutinib (Brukinsa; BeiGene, Ltd) continues to show notable benefits for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have the del(17p) mutation. The findings, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, highlight the drug’s ability to provide durable responses and improve survival rates in this high-risk patient population.

Long-Term efficacy of Zanubrutinib in CLL/SLL

treatment options for CLL/SLL have advanced considerably, yet challenges persist, especially for those with specific genetic mutations. The introduction of Bruton tyrosine kinase (BTK) inhibitors like zanubrutinib has transformed the therapeutic landscape, leading to better outcomes. Zanubrutinib, a selective BTK inhibitor, has received FDA approval for various lymphomas, including CLL/SLL. Its approval for CLL/SLL in 2023 was based on the SEQUOIA trial, which demonstrated superior progression-free survival (PFS) and overall response rate (ORR) in patients with del(17p) mutations.

Did You Know? The five-year survival rate for all cancers combined has increased from 49% in the mid-1970s to 68% between 2012 and 2018, reflecting advancements in treatment and early detection Cancer.Net.

Dr. Catherine Callaghan Coombs from the University of California, Irvine, emphasized that zanubrutinib is a highly selective next-generation BTK inhibitor designed for complete and sustained target inhibition. She noted its superiority over ibrutinib in a head-to-head phase 3 trial involving patients with high-risk del(17p) disease.

SEQUOIA Study Design and Key Endpoints

The SEQUOIA study, a global phase 3 open-label trial, randomized participants with previously untreated CLL/SLL and del(17p) to either zanubrutinib or bendamustine plus rituximab. The study comprised three arms: a randomized group (Arm A) comparing zanubrutinib to bendamustine plus rituximab, and two nonrandomized groups (Arms B and C) where patients received zanubrutinib alone or in combination with venetoclax. The primary goals were to assess PFS, ORR, overall survival (OS), and safety.

Sustained Progression-Free and Overall Survival

After a median follow-up of 65.8 months, the median PFS was not reached.The estimated 60-month PFS rate was 72.2% (95% CI, 62.4%-79.8%), or 73.0% (95% CI, 63.3%-80.6%) when adjusted for COVID-19. Similarly, the median OS was not reached, with an estimated 60-month OS rate of 85.1% (95% CI, 76.9%-90.6%), or 87.0% (95% CI, 79.0%-92.1%) with COVID-19 adjustment. The ORR was reported at 97.3%, with a complete response rate of 18.2%.

Pro Tip: Patients participating in clinical trials often receive cutting-edge treatments years before they become widely available,offering potential benefits and contributing to medical advancements.

According to Dr. Coombs, Arm C of the SEQUOIA study demonstrated that zanubrutinib combined with venetoclax shows robust efficacy and produces deep, lasting responses in treatment-naive CLL, irrespective of the presence of the del(17p) P53 mutation.

Adverse Events and Treatment Discontinuation

The most common adverse events (AEs) included any-grade infection (82%), bleeding (60%), neutropenia (19%), hypertension (18%), anemia (9%), thrombocytopenia (8%), and atrial fibrillation/flutter (7%). Grade 3 or higher AEs of interest were infection (33%),neutropenia (16%),hypertension (8%),bleeding (6%),atrial fibrillation/flutter (5%),and thrombocytopenia (2%). At the time of analysis, 62.2% of patients were still receiving zanubrutinib. The primary reasons for treatment discontinuation were AEs (17.1%) and disease progression (15.3%).

The 5-year analysis of Arm C supports the efficacy and safety of zanubrutinib for treatment-naïve patients with CLL/SLL and del(17p). Ongoing monitoring and further studies are essential to solidify zanubrutinib’s role in CLL treatment, but these initial findings are promising.

Key Metrics from the SEQUOIA Study

Endpoint	Result
Estimated 60-Month PFS Rate	72.2% (73.0% adjusted for COVID-19)
Estimated 60-Month OS Rate	85.1% (87.0% adjusted for COVID-19)
Overall Response Rate (ORR)	97.3%
Complete Response Rate	18.2%

Future Directions in CLL/SLL Treatment

As research continues, the integration of novel therapies like zanubrutinib into treatment regimens offers hope for improved outcomes and enhanced quality of life for individuals affected by CLL/SLL.The sustained efficacy and manageable safety profile observed in the SEQUOIA study underscore the potential of targeted therapies in addressing the unique challenges posed by this disease.

What are your thoughts on the role of targeted therapies in cancer treatment? How can we improve access to these innovative treatments for patients in need?

Understanding Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are types of cancer that affect white blood cells called lymphocytes. CLL primarily affects the blood and bone marrow, while SLL mainly involves the lymph nodes. Both are considered indolent, or slow-growing, cancers. According to the Leukemia & Lymphoma Society, CLL is one of the most common types of leukemia in adults.

The del(17p) mutation, characterized by the deletion of a portion of chromosome 17, is associated with poorer prognosis in CLL/SLL patients. This mutation affects the TP53 gene, which plays a crucial role in suppressing tumor growth.Patients with del(17p) often do not respond well to traditional chemotherapy, making targeted therapies like zanubrutinib particularly valuable.

Frequently Asked Questions About Zanubrutinib and CLL/SLL

What is the role of BTK inhibitors in treating CLL/SLL?

BTK inhibitors,such as zanubrutinib,target the Bruton tyrosine kinase (BTK) enzyme,which is essential for the survival and proliferation of CLL/SLL cells. By blocking BTK, these drugs can effectively slow down or stop the growth of cancer cells.

How does zanubrutinib differ from other BTK inhibitors?

Zanubrutinib is a next-generation BTK inhibitor designed to be more selective and potent than earlier drugs like ibrutinib. This selectivity may result in fewer off-target effects and improved efficacy, particularly in high-risk patients.

What should patients know about managing side effects of zanubrutinib?

Patients should be aware of potential side effects, such as infections, bleeding, and hypertension, and report any unusual symptoms to their healthcare provider. Regular monitoring and proactive management can definitely help minimize the impact of these side effects.

Are there any lifestyle changes that can support CLL/SLL treatment?

Maintaining a healthy lifestyle, including a balanced diet, regular exercise, and stress management, can support overall well-being during CLL/SLL treatment. patients should consult with their healthcare team for personalized recommendations.

What is the prognosis for CLL/SLL patients treated with zanubrutinib?

The prognosis for CLL/SLL patients treated with zanubrutinib is generally favorable, especially for those with del(17p) mutations. The SEQUOIA study demonstrated high PFS and OS rates, indicating the potential for long-term disease control and improved survival.

Disclaimer: This article provides information about a medical study and potential treatment options. It is not intended to provide medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment of any medical condition.

Share this article to spread awareness about the latest advancements in CLL/SLL treatment. What further questions do you have about zanubrutinib and its impact on CLL/SLL? Leave your comments below!

chronic lymphocytic leukemia

Pirtobrutinib Trial Shows Significant PFS Improvement in CLL/SLL