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Letters to the Editor
Acalabrutinib for treatment of diffuse large B-cell lymphoma: results from a phase Ib study
Two major molecular subtypes of diffuse large B-cell lymphoma (DLBCL), germinal center B-cell (GCB) and activated B-cell (ABC), have been defined from gene expression studies and are recognized under the World Health Organization 2016 classification.1,2 Genetic abnor- malities associated with ABC DLBCL result in chronic active B-cell receptor (BCR) signaling and NF-κB pathway activation.3 Bruton tyrosine kinase (BTK) plays a key role in the BCR signaling pathway. Covalent irreversible BTK inhibitors have recently been studied for treatment of B- cell malignancies, including relapsed/refractory (R/R) DLBCL. The response rate in a study of ibrutinib was higher in patients with ABC DLBCL than with GCB
DLBCL (37% [14 of 38] vs. 5% [one of 20]).4 Similarly, for tirabrutinib, the response rate in non-GCB DLBCL was 35% (11 of 31); neither of the two patients with GCB subtype disease responded.5 While median duration of response to ibrutinib was 4.83 months, four patients had durable complete responses (CR) >24 months.4 Acalabrutinib is approved for the treatment of patients with the B-cell malignancies of chronic lymphocytic leukemia (CLL) and R/R mantle cell lymphoma (MCL).6 It is a selective, covalent BTK inhibitor, possibly having fewer off-target biological effects and a better clinical safety profile than ibrutinib.7 The objective of this multi- center, open-label phase Ib study was to investigate the safety, pharmacokinetics, pharmacodynamics, and effica- cy of acalabrutinib monotherapy in patients with R/R non-GCB DLBCL (clinicaltrials gov. Identifier: NCT02112526). We found that the safety profile of acal-
Table 1. Incidence of treatment-emergent and treatment-related adverse events in ≥2 patients (n=21).
Preferred terma, n (%)
Diarrhea
Fatigue
Anemia
Cough
Dizziness Headache
Nausea Constipation Decreased appetite Dyspnea
Peripheral edema Arthralgia Dehydration Hypokalemia Pyrexia Abdominal pain Back pain Contusion Ecchymosis
Gait disturbance Hypomagnesemia Insomnia Musculoskeletal pain Nasopharyngitis Neck pain
Oral candidiasis Pain in extremity Petechiae Pleural effusion Rales
Rash
Respiratory failure Sinusitis
Vomiting
Treatment-Emergent Adverse Events
Treatment-Related Adverse Events
All Grades
9 (42.9) 9 (42.9) 6 (28.6) 6 (28.6) 6 (28.6) 5 (23.8) 5 (23.8) 4 (19.0) 4 (19.0) 4 (19.0) 4 (19.0) 3 (14.3) 3 (14.3) 3 (14.3) 3 (14.3) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2(9.5) 2 (9.5) 2 (9.5) 2 (9.5) 2 (9.5)
Grade ≥3 1 (4.8)
2 (9.5) 5 (23.8) -
1 (4.8) -
-
-
1 (4.8) 1 (4.8) -
1 (4.8) 1 (4.8) -
1 (4.8) 2 (9.5) -
-
-
1 (4.8) -
-
-
-
-
-
-
-
-
-
-
2 (9.5)
All Grades
4 (19.0) 4 (19.0) 3 (14.3) 3 (14.3) 5 (23.8) 2 (9.5) 2 (9.5) -
-
-
2 (9.5)
-
-
-
3 (14.3) -
-
-
-
-
-
-
-
-
-
-
-
2 (9.5) -
-
2 (9.5)
Grade ≥3 1 (4.8)
-
3 (14.3)
-
1 (4.8)
-
-
-
-
-
-
-
-
-
1 (4.8) -
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
- -
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aNational Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
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haematologica | 2021; 106(10)
