PHASE 1/2 TRIAL OF ACALABRUTINIB PLUS PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA
Author(s): ,
Thomas Witzig
Affiliations:
Mayo Clinic,Rochester,United States
,
Kami Maddocks
Affiliations:
Ohio State University,Columbus,United States
,
Sven de Vos
Affiliations:
David Geffen School of Medicine at University of California Los Angeles,Los Angeles,United States
,
Roger Lyons
Affiliations:
Texas Oncology-San Antonio Medical Center, US Oncology Research,San Antonio,United States
,
William Edenfield
Affiliations:
Greenville Health System Cancer Institute,Greenville,United States
,
Jeffrey Sharman
Affiliations:
Willamette Valley Cancer Institute and Research Center, US Oncology Research,Eugene,United States
,
Julie Vose
Affiliations:
Nebraska Medical Center,Omaha,United States
,
Habte Yimer
Affiliations:
Texas Oncology-Tyler, US Oncology Research,Tyler,United States
,
Helen Wei
Affiliations:
Acerta Pharma,South San Francisco,United States
,
Edward Chan
Affiliations:
Acerta Pharma,South San Francisco,United States
,
Priti Patel
Affiliations:
Acerta Pharma,South San Francisco,United States
,
Christopher Di Simone
Affiliations:
Arizona Oncology, US Oncology Research,Tucson,United States
,
Mitul Gandhi
Affiliations:
Virginia Cancer Specialists, US Oncology Research,Woodbridge,United States
,
Jennifer Vaughn
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States
,
Kathryn Kolibaba
Affiliations:
Northwest Cancer Specialists, US Oncology Research,Vancouver,United States
,
Bruce Cheson
Affiliations:
Georgetown University Hospital,Washington, DC,United States
Felipe Samaniego
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
EHA Library. Witzig T. Jun 15, 2019; 267449; S866
Thomas Witzig
Thomas Witzig
Contributions
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Abstract

Abstract: S866

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 16:00 - 16:15

Location: Hall 5

Background
Acalabrutinib, a highly selective, potent, covalent Bruton tyrosine kinase inhibitor, has demonstrated a 24% overall response rate as a single agent in relapsed/refractory diffuse large B-cell lymphoma. Pembrolizumab targets PD-1, an immune checkpoint that limits anticancer responses. Pembrolizumab showed responses in patients with Richter transformation who failed ibrutinib and can augment acalabrutinib activity in vitro.

Aims
To assess the efficacy and safety of the combination of acalabrutinib plus pembrolizumab for patients with relapsed/refractory diffuse large B-cell lymphoma.

Methods
Patients with diffuse large B-cell lymphoma, ≥1 prior chemoimmunotherapy, and no prior allogeneic transplant received acalabrutinib 100 mg orally twice daily until progressive disease plus pembrolizumab 200 mg/kg intravenously every 3 weeks for up to 2 years. Germinal center B-cell versus non-germinal center B-cell subtype was assessed by immunohistochemistry. The primary endpoint was safety. Secondary endpoints included investigator-assessed overall response rate per Lugano criteria, duration of response, and progression-free survival.  

Results
Sixty-one patients (30 germinal center B cell; 31 non-germinal center B cell) were accrued, with a median age of 67 years (range, 30 to 85) and a median of 3 (range, 1 to 8) prior therapies; 1 patient had prior autologous transplant. The most common grade 3/4 adverse events were neutropenia (15%) and anemia (11%). Grade 5 adverse events were respiratory failure (n=3) and sepsis, septic shock, and abdominal abscess (n=1 each). All-grade atrial fibrillation was 5% (n=3), and major hemorrhage (≥ grade 3) was 11% (4 gastrointestinal, 1 pulmonary, 1 epistaxis, and 1 hematuria). Grade 3/4 immune-mediated events were elevated alanine aminotransferase (n=4), pneumonitis (n=2), and colitis (n=1). The overall response rate was 26% (Table) and was similar in germinal center B-cell (27%) and non-germinal center B-cell (26%) tumors. The median time on study was 5.2 months (range, 0.4 to 30.4+). Acalabrutinib/pembrolizumab discontinuations were due to progressive disease (62%/56%) and adverse events (15%/26%). As of June 2018, 10 patients remain on study; 6 on active therapy and 7 without progressive disease.  

Conclusion
The combination of acalabrutinib plus pembrolizumab was well tolerated, with meaningful activity and some exceptional responders (>24 months) in these patients with relapsed/refractory diffuse large B-cell lymphoma. Randomized trials of the combination versus single agent are needed.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): DLBCL, Kinase inhibitor, Phase I/II, Targeted therapy

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