Medical Information

Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who were treated with high-frequency low-dose acalabrutinib (Calquence) and rituximab (Rituxan) demonstrated a good response, and the combination was deemed feasible, according to a presentation from the 2021 American Society of Hematology Annual Meeting.

CD20 antibodies such as rituximab primarily destroy B cells by activating the innate immune system. Standard intermittent dose rituximab may be less effective in CLL than intermittent high frequency low dose because “higher doses result in rapid exhaustion of the finite mechanisms of the innate immune system, via a reduction in phagocytosis and loss of CD20 expression due to trogocytosis,” said Wallace.

In the single-center, single-arm phase 2 study, 37 patients with CLL/SLL who were not previously treated, who required treatment based on International Workshop on CLL criteria, received rituximab at 50 mg IV on day 1 of cycle 1, followed by 50 mg subcutaneously dosing twice a week for 6 cycles. Acalabrutinib, 100 mg twice daily, was started on day 8 of cycle 1. After 6 cycles, each lasting 28 days, acalabrutinib was administered alone. Following 12 cycle, response was assessed. If MRD testing in the peripheral blood was negative, patients underwent a bone marrow biopsy to confirm CR. If a patient was MRD negative, therapy was stopped and the patient was followed until disease progression. Another repeat response assessment was performed at 24 cycles.

All 37 patients enrolled responded to the combination; however, 1 patient had a complete response but with peripheral blood testing positive for minimal residual disease (MRD), said lead study author Danielle S. Wallace, MD, in a presentation during the meeting.

The median age of patients was 67 years (range, 39.8-78.0), and 60% were male. Patients enrolled were relatively high risk, she said, with 70.2% having at least 1 high-risk feature, including 21.6% with a TP53 mutation and 13.5% with del(17p).

At a median follow-up of 14.0 months, 27 patients (73%) have completed at least 12 cycles of therapy. In addition to the 1 patient (2.7%) with a CR but peripheral blood tested that positive, there were 20 partial responses (PR; 54%) and 6 PRs with sustained lymphocytosis (16%). “To date, 10 patients have completed 24 cycles, and all were in sustained PRs at the time of their response assessment,” she said. One patient with both a del(17p) and TP53 mutation has had progressive disease following 25 cycles of therapy.

Regarding safety, grade 3/4 adverse events (AEs) occurring in at least 5% of patients were infections (13.5%), neutropenia (8.1%) and anemia (8.1%). The most common all-grade and all-causality AEs were infusion-related reactions (62.1%), infections (56.8%), fatigue (51.3%), anemia (51.3%), headache (43.2%), rash or other skin changes (32.4%), thrombocytopenia (29.7%), upper respiratory infections (29.7%), urinary tract infections (18.9%), COVID-19 pneumonia (8.1%), bruising (27.0%), and diarrhea (21.6%). None of the patients who contracted COVID-19 pneumonia required intubation and all remained on acalabrutinib during their infection.