Dr Davids on Treatment With Pirtobrutinib in CLL/SLL With/Without Prior BCL-2 Inhibitor Exposure

Matthew S. Davids, MD, MMSc, director, clinical research, Division of Lymphoma, Dana-Farber Cancer Institute, associate professor, medicine, Harvard Medical School, discusses key efficacy results from 2 follow-up analyses of the phase 1/2 BRUIN trial (NCT03740529) evaluating pirtobrutinib (Jaypirca) in patients with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL).

The BRUIN trial was a dose escalation and expansion study that enrolled adult patients with mantle cell lymphoma (n = 166), CLL/SLL ( n = 317), and other histologic subtypes (n = 295), including Richter transformation.

Extended follow-up data from a subgroup analysis

 of 282 patients with CLL or SLL, had previous exposure to a covalent BTK inhibitor, and were enrolled onto the BRUIN trial were presented at the 

, Davids begins. Notably, patients were stratified based on their exposure to a BCL-2 inhibitor, such as venetoclax (Venclexta), he says. At a median follow-up of 30 months, patients treated with pirtobrutinib experienced a high objective response rate (ORR) with pirtobrutinib regardless of prior BCL-2 inhibitor exposure, Davids reports. The ORR in the total population was 81.6% (95% CI, 76.5%-85.9%). Patients who were naive to BCL2 inhibition (n = 154) achieved an ORR with pirtobrutinib of 83.1% (95% CI, 76.2%-88.7%) and patients who had prior exposure to BCL-2 inhibitors (n = 128) achieved an ORR of 79.7% (95% CI, 71.7%-86.3%) with the agent.

Moreover, the median progression-free survival (PFS) with pirtobrutinib in patients who previously received covalent BTK inhibitors was 19.4 months (95% CI, 16.6-22.1), Davids details. The median PFS in the BCL2 inhibitor–naive group was 23.0 months (95% CI, 19.6-28.4) compared with 15.9 months (95% CI, 13.6-17.5) in the BCL2 inhibitor–exposed group.

These updated data have implications for treatment with pirtobrutinib, shedding light on potential considerations based on prior treatment history, Davids states. The durability of responses with pirtobrutinib also affirms its efficacy in patients with CLL/SLL, he adds.

Updated results with pirtobrutinib in patients with Richter transformation (n = 82) were also presented at the meeting, Davids continues. Patients with Richter transformation are typically underrepresented in clinical trial populations, as it is a relatively rare disease, Davids says, adding that the majority of patients in this cohort had been previously treated for Richter transformation and were thus classified as having high-risk disease.

In this presentation, pirtobrutinib produced an ORR of 50.0% (95% CI, 38.7%-61.3%); this was consistent with early data that were previously reported at the 2022 ASH Annual Meeting, Davids details. Despite eliciting a modest median PFS of 3.7 months (95% CI, 2.7-4.9), the agent led to a median overall survival of 12.5 months (95% CI, 6.9-20.5) in the overall Richter transformation population at a median follow-up of 18.3 months.

This indicates that pirtobrutinib could serve as effective bridging therapy until subsequent therapies like CAR T-cell therapy or allogeneic transplantation can occur, Davids asserts. Additionally, the drug’s favorable ORR positions it as a promising partner for combination therapies targeting Richter transformation, he says, and ongoing studies are exploring such combinations.

The evolving landscape of pirtobrutinib's role in Richter transformation, especially in combination approaches, underscores its potential significance in addressing this challenging malignancy, Davids concludes. 

Videos

Matthew S. Davids, MD, MMSc, discusses key efficacy results from 2 follow-up analyses of the phase 1/2 BRUIN trial evaluating pirtobrutinib.

Data from the following clinical trials are discussed:

3721: Characterization of Bruton tyrosine kinase inhibitor (BTKi)-related adverse events in a head-to-head trial acalabrutinib versus ibrutinib in previously chronic lymphocytic leukemia (CLL)

68: First-line treatment with ibrutinib (Ibr) plus venetoclax (Ven) for chronic lymphocytic leukemia (CLL): 2-year post-randomization disease-free survival (DFS) results from the minimal residual disease (MRD) cohort of the phase 2 Captivate study

396: SEQUOIA: Results of a phase 3 randomized study of zanubrutinib versus bendamustine + rituximab (BR) in patients with treatment-naïve (TN) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)

67: Zanubrutinib in combination with venetoclax for patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with del(17p): early results from arm D of the SEQUOIA (BGB-311-304) trial

1410: Phase 2 study of zanubrutinib in BTK inhibitor-intolerant patients (Pts) with relapsed/refractory B-cell malignancies

395: A phase 2 study evaluating the addition of ublituximab and umbralisib (U2) to ibrutinib in patients with chronic lymphocytic leukemia (CLL): a minimal residual disease (MRD)-driven, time-limited approach

391: Pirtobrutinib, a next generation, highly selective, non-covalent BTK inhibitor in previously treated CLL/SLL: updated results from the phase 1/2 BRUIN study

Supported in part by Takeda Oncology. Content developed independently by Onclive®.

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ASH 2021: Updates in the Chronic Lymphocytic Leukemia Treatment Landscape 

310: Efficacy and safety results from ASCEMBL, a multicenter, open-label, phase 3 study of asciminib, a first-in-class STAMP inhibitor, vs bosutinib in patients with chronic myeloid leukemia in chronic phase after ≥2 tyrosine kinase inhibitors: update after 48 weeks

307: Post hoc analysis of responses to ponatinib in patients with chronic-phase chronic myeloid leukemia (CP-CML) by baseline 

 level and baseline mutation status in the Optic trial

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ASH 2021: Key Data in Chronic Myeloid Leukemia 

1233: Updated results from a phase I study of hyper-CVAD with sequential blinatumomab in adults with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia

1231: Superior overall survival with blinatumomab versus chemotherapy as pre-transplant consolidation treatment in children with high-risk first-relapse B-cell precursor acute lymphoblastic leukemia (B-ALL): longer follow-up (FU) of a phase 3 randomized controlled trial (RCT)

4028: Successful outpatient administration of blinatumomab infusion in pediatric patients with acute lymphoblastic leukemia

516: Isatuximab in combination with chemotherapy in pediatric patients with relapsed/refractory acute lymphoblastic leukemia or acute myeloid leukemia (ISAKIDS): interim analysis

428: Real-world outcomes for pediatric and young adult patients with relapsed refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) treated with tisagenlecleucel: update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

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ASH 2021: Novel Therapy in Acute Lymphocytic Leukemia 

A discussion on updates presented at the ASH (American Society of Hematology) 2020 Annual Meeting on developments in the management of relapsed/refractory B-cell lymphomas.

Abstract 339: Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory Marginal Zone Lymphoma: Initial Results of the MAGNOLIA (BGB-3111-214) Trial

Abstract 403: Glofitamab Step-up Dosing Induces High Response Rates in Patients with Hard-to-Treat Refractory or Relapsed Non-Hodgkin Lymphoma

Abstract 2104: A Phase I Investigator Sponsored Trial of Selinexor (KPT-330) and Rituximab, Ifosfamide, Carboplatin and Etoposide in Patients with Relapsed or Refractory Aggressive B-Cell Lymphomas

Abstract 599: Polatuzumab Vedotin Plus Venetoclax with Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Primary Efficacy Analysis of a Phase Ib/II Study

Abstract 598: Phase 1b/2 Study of Vipor (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide) in Relapsed/Refractory B-Cell Lymphoma: Safety, Efficacy and Molecular Analysis

ASH 2020 Updates in Relapsed/Refractory B-Cell Lymphomas

Key opinion leaders provide insight into data updates from the ASH (American Society of Hematology) 2020 Annual Meeting on developments in agents for the management of non-CLL (chronic lymphocytic leukemia) B-cell lymphomas.

Abstract 2109: Selinexor in Combination with R-CHOP for Front-Line Treatment of Non-Hodgkin Lymphoma: Results of a Phase 1b Study

Abstract 405: Interim Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) as First-Line Therapy in Patients (Pts) With High-Risk Large B Cell Lymphoma (LBCL)

ASH 2020 Updates in Non-CLL B-Cell Lymphomas

Experts in the management of hematologic malignancies discuss various abstracts and data updates presented at the ASH (American Society of Hematology) 2020 Annual Meeting on chronic lymphocytic leukemia (CLL).

Abstract 123: Ibrutinib (Ibr) Plus Venetoclax (Ven) First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): 1-Year Disease Free Survival (DFS) Results From the MRD Cohort of the Phase 2 CAPTIVATE Study 

Abstract 1318: Zanubrutinib in Combination with Venetoclax for Patients with Treatment Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma and del(17p) Arm D of the SEQUOIA (BGB-3111-304) Trial

Abstract 125: Five-Year Analysis of Murano Study Demonstrates Enduring Undetectable Minimal Residual Disease (uMRD) in a Subset of Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) Patients (Pts) Following Fixed-Duration Venetoclax-Rituximab (VenR) Therapy (Tx)

Woyach Abstract 1305: Three-Year Follow-Up from a Phase 2 Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Chronic Lymphocytic Leukemia

Abstract 2216: Updated Safety and Efficacy Results from a Phase 2 Study of Acalabrutinib, Venetoclax and Obinutuzumab (AVO) for Front-Line Treatment of Chronic Lymphocytic Leukemia (CLL)

Abstract 544: Transcend CLL 004: Phase 1 Cohort of Lisocabtagene Maraleucel (liso-cel) in Combination with Ibrutinib for Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Abstract 545: Safety and Efficacy of CD19-CAR T Cells in Richter’s Transformation after Targeted Therapy for Chronic Lymphocytic Leukemia

Matthew S. Davids, MD, MMSc, Dana-Farber Cancer Institute

Articles

Dr Davids on Treatment With Pirtobrutinib in CLL/SLL With/Without Prior BCL-2 Inhibitor Exposure

ASH 2021: Updates in the Chronic Lymphocytic Leukemia Treatment Landscape

ASH 2021: Key Data in Chronic Myeloid Leukemia

ASH 2021: Novel Therapy in Acute Lymphocytic Leukemia

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