Dr Awan on Treatment Considerations With Pirtobrutinib in Hematologic Malignancies

“For now, noncovalent BTK inhibitors should be used only after [progression on] covalent BTK inhibitors and a BCL-2 inhibitor.”

Farrukh Awan, MD, professor, Department of Internal Medicine, member, Division of Hematology and Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses treatment considerations with the use of pirtobrutinib (Jaypirca) in previously treated patients with hematologic malignancies.

The emergence of pirtobrutinib, along with other noncovalent BTK inhibitors, represents a promising advancement, particularly for patients refractory to prior BTK inhibitor therapies, Awan begins. These agents have demonstrated encouraging efficacy, especially in patients intolerant to covalent BTK inhibitors, as these patients tend to respond better than those with true BTK inhibitorresistance, he explains. Similarly, outcomes are generally favorable if the patient has been exposed to, but not rendered refractory by, BTK and BCL-2 inhibitors, according to Awan. However, for patients who are refractory to both BTK and BCL-2 inhibitors, the responses to noncovalent BTK inhibitors, although decent, tend to be less durable, Awan emphasizes. This is an important consideration; pirtobrutinib and similar agents are valuable treatment options but they may not consistently deliver long-lasting remissions, he says.

Another key point is the relatively limited understanding of resistance mechanisms associated with these newer therapies. he continues. Early data from small studies indicate evolving resistance patterns, but more extensive research is needed, he notes. What is currently known is that patients exposed to noncovalent BTK inhibitors may develop resistance mutations that render covalent BTK inhibitors ineffective, he states, noting that this highlights the importance of sequencing therapies carefully to optimize patient outcomes.

Based on current evidence, noncovalent BTK inhibitors should be reserved for patients who have already progressed on covalent BTK inhibitors and BCL-2 inhibitors, he reiterates. Using noncovalent BTK inhibitors earlier in the treatment sequence may limit future options due to cross-resistance, he explains. As more data become available, these recommendations may evolve, but for now, careful treatment sequencing remains critical, Awan concludes.

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Farrukh Awan, MD, discusses treatment considerations with the use of pirtobrutinib in previously treated patients with hematologic malignancies.

Farrukh Awan, MD, an associate professor in the Department of Internal Medicine at UT Southwestern Medical Center (UTSW), and a member of the Division of Hematology and Oncology at UTSW's Harold C. Simmons Comprehensive Cancer Center and William P. Clements Jr. University Hospital, discusses the importance of collaborative care in chronic lymphocytic leukemia (CLL).

The field of CLL continues to excel forward with novel molecular biomarkers​, new therapeutic options, and ongoing clinical trials, says Awan.

Despite this, CLL remains a complex disease, Awan adds. As such, closely ​collaboration between community oncologists and CLL experts is often necessary to ensure patients receiv​e optimal care.

Moreover, ​individuals who treat many cases of CLL may be able to recommend ongoing clinical trials that community oncologists are not aware of, Awan adds.

Ultimately, ​collaborative care is needed to identify new treatment​s and testing options, and to improve upon available therapies, Awan concludes.

Farrukh Awan, MD, discusses the importance of collaborative care in chronic lymphocytic leukemia.





Dr. Awan on the Importance of Collaborative Care in CLL

Farrukh Awan, MBBS, associate professor, The Ohio State University Comprehensive Cancer Center, discusses the importance of fluorescence in situ hybridization (FISH) testing for patients with chronic lymphocytic leukemia (CLL). 

According to Awan, the most critical area in CLL is the underutilization of FISH and IGVH testing. That is essential to prognosticating patients and critical to selecting the right therapy. 

Based on market data, this is not being done universally and it is an area that needs improvement, says Awan. 

Farrukh Awan, MBBS, associate professor, The Ohio State University Comprehensive Cancer Center, discusses the importance of fluorescence in situ hybridization (FISH) testing for patients with chronic lymphocytic leukemia (CLL).

Dr. Awan on the Importance of FISH Testing in CLL

Farrukh Awan, MBBS, associate professor, The Ohio State University Comprehensive Cancer Center, discusses combinations with ibrutinib (Imbruvica) in chronic lymphocytic leukemia (CLL).

Combinations with ibrutinib have shown to be effective, but have not been proven to be superior to ibrutinib alone, says Awan.

The ALLIANCE trial compared ibrutinib to ibrutinib plus rituximab and chemoimmunotherapy, results of which could clarify the argument of monotherapy versus combination.

Farrukh Awan, MBBS, associate professor, The Ohio State University Comprehensive Cancer Center, discusses combinations with ibrutinib (Imbruvica) in chronic lymphocytic leukemia. 

Dr. Awan Discusses Combinations With Ibrutinib in CLL

Farrukh Awan, MBBS, associate professor, The Ohio State University Comprehensive Cancer Center, discusses challenges with ibrutinib (Imbruvica) in chronic lymphocytic leukemia (CLL).

The key issues with usage of ibrutinib in patients with CLL are duration and the management of side effects.

Current ongoing trials are tackling these challenges, says Awan, results of which will hopefully bring more knowledge to the field.

Farrukh Awan, MBBS, associate professor, The Ohio State University Comprehensive Cancer Center, discusses challenges with ibrutinib (Imbruvica) in chronic lymphocytic leukemia. 

Dr. Awan Discusses Challenges With Ibrutinib in CLL

Farrukh Awan, MBBS, associate professor, The Ohio State University Comprehensive Cancer Center, discusses venetoclax (Venclexta) in chronic lymphocytic leukemia (CLL).

Venetoclax has been approved for relapsed patients with CLL who have a 17p deletion. As a single agent, it is very effective, potent, and induces deep remissions, says Awan.

Based on its success, it is starting to be tested in combinations.

Farrukh Awan, MBBS, associate professor, The Ohio State University Comprehensive Cancer Center, discusses venetoclax (Venclexta) in chronic lymphocytic leukemia.

Dr. Awan Discusses Venetoclax in CLL

Farrukh Awan, MBBS, assistant professor of internal medicine, Ohio State University, discusses the role for spleen tyrosine kinase (Syk) inhibitor for the treatment of chronic lymphocytic leukemia (CLL).

Therapy for CLL patients that have failed kinase inhibitors is not very well defined. There is a great need for an agent for patients that have relapsed after either PI3 kinase or bruton's tyrosine kinase (BTK) inhibitors, says Awan.

Syk inhibitor, a compound that is located upstream of BTK and is part of the B-cell receptor signaling pathway, may be a promising option for relapsed patients.

Early results have shown that it is active and well-tolerated in CLL. Syk inhibitor has the potential to maintain quality of life and provide decease control for patients who rapidly progress after failing kinase inhibitors, says Awan.

Farrukh Awan, MBBS

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