Combination of Zanubrutinib + Venetoclax for Treatment-naive CLL/SLL With del(17p) and/or TP53: Preliminary Results From SEQUOIA Arm D

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Preliminary results for treatment with zanubrutinib + venetoclax in patients with high-risk TN CLL/SLL with del(17p) and/or TP53 mutation showed Promising efficacy in a high-risk population with deep and durable responses according to data from arm D of the phase 3 SEQUOIA trial (NCT03336333).

Shuo Ma, MD, PhD, associate professor of Medicine, Hematology and Oncology, Feinberg School of Medicine, Northwestern University, discusses the utilization of zanubrutinib (Brufkinsa) in chronic lymphocytic leukemia (CLL).

Zanubrutinib has found a role in everyday practice, such as in patients who have continued to benefit from inhibition of the BTK pathway but have developed an intolerance to ibrutinib (Imbruvica), Ma explains. Moreover, zanubrutinib is beneficial in patients who are not candidates for acalabrutinib (Calquence), including those patients who need to remain on a proton pump inhibitor and need long-term antacid medication, Ma adds.

The administration of zanubrutinib in these situations has proved to be favorable in practice, Ma concludes.

Shuo Ma, MD, PhD, discusses the utilization of zanubrutinib in chronic lymphocytic leukemia.


Dr. Ma on Utilizing Zanabrutinib in CLL

Shuo Ma, MD, PhD, an associate professor of medicine (hematology and oncology), Robert H. Lurie Comprehensive Cancer Center, ​Northwestern University Feinberg School of Medicine, discusses the need to develop novel agents to treat patients with chronic lymphocytic leukemia (CLL) who develop resistance to BTK inhibitors.

Although the introduction of BTK inhibitors to the CLL armamentarium has been transformative, questions remain, Ma says. For example, additional research is needed to determine the mechanism of resistance for BTK inhibitors, as well as the optimal treatment for patients who develop resistance. 

In CLL, some mutations, such as those in the BTK enzyme, confer resistance to first- or second-generation BTK inhibitors, says Ma.

As such, third-generation, reversible BTK inhibitors that are currently in development may be able to overcome resistance, concludes Ma.

Shuo Ma, MD, PhD, discusses the need to develop novel agents to treat patients with chronic lymphocytic leukemia who develop resistance to BTK inhibitors.  



Dr. Ma on Developing Novel Agents in BTK Inhibitor–Resistant CLL 

Shuo Ma, MD, PhD, an associate professor of medicine (hematology and oncology), Robert H. Lurie Comprehensive Cancer Center, ​Northwestern University Feinberg School of Medicine, discusses the utility of BTK inhibitors in relapsed/refractory chronic lymphocytic leukemia (CLL).

The course of treatment with BTK inhibitors depends on the type of disease, says Ma. For example, in CLL, ibrutinib (Imbruvica) and acalabrutinib (Calquence) are approved for use in both the frontline and relapsed settings. In terms of how these agents are being used in a clinical setting, they are becoming some of the field’s major first-line treatment options, according to Ma.

Over the past several years, many large, randomized clinical trials have compared BTK inhibitor-based therapies with conventional chemoimmunotherapy. BTK inhibitors have shown significant benefit in terms of progression-free survival, even when compared with the best chemoimmunotherapy regimens available, concludes Ma.

Shuo Ma, MD, PhD, discusses the utility of BTK inhibitors in relapsed/refractory chronic lymphocytic leukemia.

Dr. Ma on the Utility of BTK Inhibitors in Relapsed/Refractory CLL

Shuo Ma, MD, PhD, associate professor of medicine (hematology and oncology), Robert H. Lurie Comprehensive Cancer Center, ​Northwestern University Feinberg School of Medicine, highlights ongoing ​research with BTK inhibitor​s in B​-cell malignancies. 

Currently, the BTK inhibitors ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) ​have indications in chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström macroglobulinemia, ​says Ma. Ibrutinib is a first-generation BTK inhibitor, whereas acalabrutinib and zanubrutinib are second-generation ​BTK inhibitors.

Ibrutinib​ inhibits the BTK enzyme, which is a critical component of B​-cell biology, survival, and proliferation. However, ibrutinib affects other tyrosine kinases, such as EGFR​, Ma explains.

As a result, patients may experience off-target toxicities with ibrutinib, ​adds Ma.

​Although head-to-head clinical trials are needed, acalabrutinib and zanubrutinib may elicit less toxicity compared with ibrutinib as the agents are more selective, Ma concludes.

Shuo Ma, MD, PhD, highlights ongoing ​research with BTK inhibitor​s in B​-cell malignancies. 

Dr. Ma on First- and Second-Generation BTK Inhibitors in B-Cell Malignancies

Shuo Ma, MD, PhD, assistant professor at Northwestern University in the Robert H. Lurie Comprehensive Cancer Center, discusses advances in non-chemotherapy regimens for patients with hematologic malignancies.

Rituximab in combination with bortezomib and rituximab in combination with lenalidomide have shown success for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma . Both combinations provide a fairly high response rate in both the frontline setting and the relapse setting, says Ma.

B-cell receptor pathway inhibitors including ibrutinib and idelalisib also offer exciting benefits. Both have shown significant activity across many different forms of b-cell malignancies.

View more from the 2015 Congress on Hematologic Malignancies

Shuo Ma, MD, PhD, assistant professor at Northwestern University in the Robert H. Lurie Comprehensive Cancer Center discusses advances in non-chemotherapy regimens for patients with hematologic malignancies.

Shuo Ma, MD, PhD

Articles

Combination of Zanubrutinib + Venetoclax for Treatment-naive CLL/SLL With del(17p) and/or TP53: Preliminary Results From SEQUOIA Arm D

Dr. Ma on Utilizing Zanabrutinib in CLL

Dr. Ma on Developing Novel Agents in BTK Inhibitor–Resistant CLL

Dr. Ma on the Utility of BTK Inhibitors in Relapsed/Refractory CLL

Dr. Ma on First- and Second-Generation BTK Inhibitors in B-Cell Malignancies

Dr. Shuo Ma on Non-Chemotherapy Regimens for Hematologic Malignancies