Meghan Thompson, MD, third-year fellow, Hematology and Medical Oncology, Memorial Sloan Kettering Cancer Center, discusses the rationale for the phase 1/2 BRUIN study (NCT03740529) in patients with Richter transformation. 

Richter transformation is a rare, but serious complication that arises in a small subgroup of patients with CLL, Thompson says. Moreover, the disease can transform into a more aggressive lymphoma, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, Thompson adds. Patients with Richter transformation are considered high risk and have an estimated overall survival ofbetween 3 and 11 months, Thompson explains.

Moreover, the standard of care treatment is not clear for these patients, Thompson continues. However, the BRUIN study evaluated a novel approach to treating patients with Richter transformation with pirtobrutinib (LOXO-305), Thompson concludes.


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Meghan Thompson, MD, discusses the rationale for the phase 1/2 BRUIN study in patients with Richter transformation. 








Dr. Thompson on the Rationale for the BRUIN Study in Richter Transformation 

Meghan Thompson, MD, third-year fellow, Hematology and Medical Oncology, Memorial Sloan Kettering Cancer Center, discusses the safety profile of pirtobrutinib (LOXO-305) in patients with Richter transformation. 

Findings from the phase 1/2 BRUIN study (NCT03740529) demonstrated a 67% overall response rate with pirtobrutinib, a noncovalent, oral BTK inhibitor, among 15 evaluable patients with Richter transformation. 

Regarding safety, pirtobrutinib was well tolerated among patients, and toxicities were generally consistent with those observed in the overall patient population, which included patients with previously treated, advanced B-cell malignancies. In the Richter transformation cohort, the most common treatment-emergent adverse effects included neutrophil count decrease and diarrhea. 

Notably, none of the 17 patients with Richter transformation discontinued pirtobrutinib because of toxicity. A dose reduction of pirtobrutinib from 200 mg daily to 100 mg daily was required in 1 patient because of toxicity, Thompson concludes. 

Meghan Thompson, MD, discusses the safety profile of pirtobrutinib in patients with Richter transformation.  



Dr. Thompson on the Safety Profile of Pirtobrutinib in Patients With Richter Transformation 

Meghan Thompson, MD, third-year fellow, Hematology and Medical Oncology, Memorial Sloan Kettering Cancer Center, discusses the results of the phase 1/2 BRUIN study (NCT03740529) in patients with Richter transformation. 

Findings from the BRUIN trial, which were presented during the 2021 International Workshop on CLL, showed that the investigational noncovalent BTK inhibitor pirtobrutinib (LOXO-305) elicited an overall response rate of 67%, which comprised 2 complete responses and 8 partial responses, among 15 evaluable patients with Richter transformation.

The presence of Richter transformation is associated with high-risk disease and poor outcomes, Thompsons says. Additionally, the patients included on the BRUIN study received a median of 4 prior lines of therapy for chronic lymphocytic leukemia prior to Richter transformation and a median of 2 prior lines of Richter transformation–directed therapy. Therefore, this population had very high-risk, heavily pretreated disease.

Additional results showed that the median time to best response was 1.9 months (range, 1.6-2.1), Thompson adds. Although longer follow-up is needed, these data suggest a promising role for pirtobrutinib in patients with Richter transformation, Thompson concludes. 

Meghan Thompson, MD, discusses the results of the phase 1/2 BRUIN study in patients with Richter transformation.  



Dr. Thompson on the Results of the BRUIN Study in Patients With Richter's Transformation 

Meghan Thompson, MD, third-year fellow, Hematology and Medical Oncology, Memorial Sloan Kettering Cancer Center, discusses the evolving role of minimal residual disease (MRD) testing in chronic lymphocytic leukemia (CLL).

The role of MRD testing has grown substantially in CLL in the past 5 years, Thompson says. Although MRD negativity is not typically a primary end point in clinical trials, more recent studies are incorporating it as a secondary end point, Thompson explains. As a result, significant data regarding how MRD negativity and MRD kinetics affect progression-free survival and patient outcomes have emerged, Thompson says. 

However, routine MRD testing is not standard of care for patients with CLL and assay availability varies significantly between academic centers, community centers, and global centers, Thompson explains. As additional data emerge, centers are likely to adopt MRD testing as a routine clinical practice to guide therapy for patients with CLL, Thompson concludes.

Meghan Thompson, MD, discusses the evolving role of minimal residual disease testing in chronic lymphocytic leukemia.



Dr. Thompson on the Evolving Role of MRD Testing in CLL 

Meghan Thompson, MD, third-year fellow, Hematology and Medical Oncology, Memorial Sloan Kettering Cancer Center, discusses future research directions in chronic lymphocytic leukemia (CLL).

Although several therapies are available to treat patients with CLL, many patients experience disease progression, Thompson says. As such, developing a greater understanding of how to best tailor available therapies to patients is of paramount importance, Thompson explains. 


Additionally, the development of improved treatment sequencing of monotherapies or combinations could further improve outcomes for patients with CLL, Thompson concludes.

Meghan Thompson, MD, discusses future research directions in chronic lymphocytic leukemia. 



Dr. Thompson on Future Research Directions in CLL 

Meghan Thompson, MD, third-year fellow, Hematology and Medical Oncology, Memorial Sloan Kettering Cancer Center, discusses emerging treatment strategies with BTK inhibitors in chronic lymphocytic leukemia (CLL).

Significant data are emerging with BTK inhibitor–based treatment strategies in CLL, says Thompson. Single-agent zanubrutinib (Brukinsa) could offer a third single-agent BTK inhibitor option for this patient population that could yield a more favorable safety profile compared with ibrutinib (Imbruvica) and acalabrutinib (Calquence), Thompson says.

Additionally, non-covalent BTK inhibitors are emerging as potential treatments, but additional data are needed to determine where these agents will fit into sequencing among the covalent BTK inhibitors, as well as venetoclax (Venclexta), Thompson explains.

Combination strategies with BTK inhibitors are also an exciting advancement in CLL, Thompson says. For example, data from the primary analysis of the fixed-duration cohort of the phase 2 CAPTIVATE study (NCT02910583) were presented during the 

. Patients with treatment-naïve CLL or small lymphocytic lymphoma received a 3-cycle lead-in dose of ibrutinib followed by 12 cycles of ibrutinib plus venetoclax, Thompson says. The overall response rate was 96% in all treated patients, Thompson says. 

As such, fixed-duration therapy offers an appealing strategy for patients with CLL who would prefer to have a treatment-free remission vs receive continuous therapy, Thompson concludes.

Meghan Thompson, MD, discusses emerging treatment strategies with BTK inhibitors in chronic lymphocytic leukemia.



Meghan Thompson, MD

Articles

Dr. Thompson on the Rationale for the BRUIN Study in Richter Transformation

Dr. Thompson on the Safety Profile of Pirtobrutinib in Patients With Richter Transformation

Dr. Thompson on the Results of the BRUIN Study in Patients With Richter's Transformation

Dr. Thompson on the Evolving Role of MRD Testing in CLL

Dr. Thompson on Future Research Directions in CLL

Dr. Thompson on Emerging Treatment Strategies With BTK Inhibitors in CLL