acp-196 and Purpura

This multicenter, open-label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three-part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well-tolerated in adult Japanese patients with B-cell malignancies.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Benzamides; Drug Administration Schedule; Female; Headache; Humans; Japan; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Male; Middle Aged; Neoplasm Recurrence, Local; Purpura; Pyrazines; Survival Analysis; Treatment Outcome

Acalabrutinib is a second-generation, highly selective Bruton's Tyrosine Kinase inhibitor (BTKi) indicated for use in some mature B-cell malignancies. The authors describe a uniquely distributed drug reaction presenting as palpable purpura over the bilateral upper limbs. BTKi is theorised to cause haemorrhage through off-target inhibition of Tec kinases and EGFR receptors. Dermatologists play an integral role in the multidisciplinary management of these patients to limit the negative impact on patient quality of life and, more importantly, to restrict dose reduction or treatment discontinuation.

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Benzamides; Drug Eruptions; Humans; Piperidines; Protein Kinase Inhibitors; Purpura; Pyrazines; Quality of Life