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Acalabrutinib plus lenalidomide and rituximab displayed activity and had a tolerable safety profile in first-line follicular lymphoma.
Frontline acalabrutinib (Calquence) in combination with lenalidomide (Revlimid) and rituximab (Rituxan) was safe and effective for the treatment of patients with advanced-stage follicular lymphoma with high tumor burden, according to data from a phase 2 study (NCT04404088) published in Nature Communications.1
At a median follow-up of 43 months (95% CI, 41-47), patients who received the triplet (n = 24) achieved a best complete response (CR) rate of 92% (95% CI, 73%-99%) after 6 cycles of treatment; this figure increased from 62.5% after 3 cycles. The best CR rate per CT was 83% (95% CI, 65%-93%).
The median progression-free survival (PFS) was not reached (NR); the 2- and 3-year PFS rates were 79% (95% CI, 65%-97%) and 62% (95% CI, 45%-85%), respectively. The median overall survival (OS) was also NR, and the 2- and 3-year OS rates were 92% (95% CI 81%-100%) and 87% (95% CI, 75%-100%), respectively.
“The results of this phase 2 study indicate that the addition of acalabrutinib to lenalidomide and rituximab is a safe and effective frontline nonchemotherapy regimen for patients [with] follicular lymphoma with an indication for treatment, resulting in high and early CR rates,” Paolo Strati, MD, and coauthors wrote in the publication.
Strati is an associate professor in the Department of Lymphoma/Myeloma and the Department of Translational Molecular Pathology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, as well as an international faculty member in the Department of PhD Program in Clinical and Experimental Oncology and Immunology at the University of Padova in Padua, Italy.
Eligible patients received oralacalabrutinib at a lead-in dose of 100 mg twice daily for a single 28-day cycle; acalabrutinib treatment then continued in combination with lenalidomide and rituximab for a total of 13 cycles.1 Oral lenalidomide was given at 20 mg daily on days 1 through 21 during cycles 2 through 13, and intravenous rituximab was administered at 375 mg/m2 weekly during cycle 2 and on day 1 of cycles 3 through 13.
The primary end point was CR rate assessed by PET-CT. Secondary end points included ORR, CR rate at 30 months (CR30), PFS, OS, relapse-free survival, safety, and tolerability. The effect of acalabrutinib monotherapy and of the triplet combination on circulating immune cells, as well as minimal residual disease (MRD) per circulating tumor DNA, were evaluated as exploratory end points.
At baseline, the median age was 62 years (range, 40-82). Most patients were White (92%), male (75%), had grade 1 to 2 disease (92%), did not have B-symptoms (96%), had Ann Arbor stage IV disease (79%), and had extranodal disease (83%). The median hemoglobin level was 13.5 g/dL (range, 11.8-15.8), and the median number of treatment cycles was 13 (range, 6-13).
Additional findings from the study revealed that among 23 patients who were evaluable for early disease progression, the CR30 rate was 65%, and the rate of disease progression within 24 months was 17%. Among evaluable patients (n = 22), the MRD negativity rate after 6 cycles of treatment was 73%. No patients with a partial response achieved MRD negativity. Eighty-one percent (n = 13/16) patients without detectable MRD following 6 cycles of therapy remained in CR.
In terms of safety, the most frequent any-grade adverse effects (AEs) included neutropenia (91%), anemia (83%), fatigue (79%), thrombocytopenia (67%), and headache (58%). The most common grade 3 to 4 treatment-emergent AEs included neutropenia (58%), elevated aspartate aminotransferase levels (12.5%), infections (12.5%), anemia (8%), and skin rash (8%).
“To further explore its activity and to investigate a shorter duration of treatment, the study has been expanded to include [an] additional 26 patients [with] follicular lymphoma,” Strati and coauthors wrote in their conclusion. “An exploratory cohort of 10 patients with marginal zone lymphoma has also been included. [Although] randomized phase 3 trials investigate the efficacy of anti-CD3/CD20 bispecific antibodies in the frontline setting, and regimens combining other BTK inhibitors and anti-CD20 monoclonal antibodies show promising efficacy in the salvage setting, acalabrutinib, lenalidomide, and rituximab represents a safe and effective chemotherapy-free regimen.”
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