Zanubrutinib plus R-BAP produced responses in both younger and older patients with previously untreated mantle cell lymphoma.
Zanubrutinib (Brukinsa) combined with R-BAP (rituximab [Rituxan], bendamustine, cytarabine, and prednisone), followed by zanubrutinib maintenance, produced high response rates in patients with previously untreated mantle cell lymphoma (MCL), according to findings from a prospective, observational, multicenter, investigator-initiated study (NCT05506410) presented at the
Among patients with previously untreated MCL younger than 65 years of age (n = 12), overall response rates (ORR) and complete response (CR) rates were both 91.7%, including 3 patients with blastoid variant disease. At a median follow-up of 20 months (range, 6-41), the median progression-free survival (PFS) for these patients was not reached (NR); the estimated 1- and 2-year PFS rates were 100% and 87.5%, respectively. Median overall survival (OS) was also NR, and all patients in the younger cohort were alive at data cutoff.
Patients with previously untreated MCL who were 65 to 75 years of age (n = 6) achieved an ORR and CR rate of 83.3%, including 1 patient who achieved a CR during zanubrutinib maintenance. At a median follow-up of 14 months (range, 5-33), 1 patient with blastoid variant disease experienced disease progression at 5 months; median PFS was NR, and the estimated 1-year PFS rate was 83.3%. The 1-year OS rate was 100% in this cohort.
“In patients with treatment-naive MCL, zanubrutinib combined with R-BAP followed by zanubrutinib maintenance demonstrated encouraging efficacy and a manageable safety profile,” lead study author Jieming Zhang, MD, an associate professor in the Department of Oncology at the First Affiliated Hospital of Zhengzhou University in China, and colleagues wrote in a poster presentation of the data.
Investigators of the trial sought to evaluate both efficacy and safety of treatment regimens with zanubrutinib in patients with previously untreated MCL.
The open-label, multicenter study enrolled patients at least 18 years of age with previously untreated MCL and an ECOG performance status of 2 or less.2 Patients also needed to have an acceptable hematological index without chemotherapy contraindications, at least one measurable lesion, normal heart function, and kidney function defined as serum creatinine of at least 1.5 time the upper level of normal.
If patients had definite neuropathy or psychosis, participated in clinical trials within 4 weeks of enrollment, systemic autoimmune disease, or primary or secondary central tumors, they were not included in the trial.
Patients in the younger cohort received zanubrutinib at 160 mg twice daily, a 375 mg/m² dose of rituximab on day 0, bendamustine at 70 mg/m² on days 1 and 2, cytarabine at 400 mg/m² on days 1 to 3, and prednisone at 100 mg on days 1 to 5 of 28-day cycles for 6 cycles.
Patients in the older cohort started with R-BAP alone, with bendamustine at 70 mg/m² on day 0, cytarabine at 300 mg/m² on days 1 to 3, and prednisone at 60 mg on days 1 to 5 of 28-day cycles for the first 4 cycles. After receiving R-BAP, patients in the older cohort underwent 4, 21-day cycles of twice daily, 160-mg doses of zanubrutinib plus a 375 mg/m2 dose of rituximab on day 1 of each cycle.
Patients in both cohorts then received zanubrutinib maintenance at 160 mg twice daily for 12 months.
Notably, 12 of the 19 younger patients completed all 6 cycles of zanubrutinib plus R-BAP and were evaluable for efficacy, and all 6 older patients were evaluable.
The primary end point of the study was PFS, whereas secondary end points included ORR, CR rate, and OS.
Baseline characteristics revealed that patients in the younger cohort had a median age of 57 (range, 39-64) compared with 70 years (range, 66-72) for the older cohort. Moreover, most patients in the younger cohort were male (66.7%) compared with only half in the older cohort (50%).
High- or intermediate-high-risk disease by simplified MCL International Prognostic Index score was more common in the older cohort (50%) than the younger cohort (16.7%). A Ki-67 proliferation index of at least 30% was observed in 75% of younger patients and 83.3% of older patients, additonally blastoid variant histology was present in 25% of younger patients and 33.3% of older patients.
In the younger cohort, the most frequent grade 3 or higher treatment-related adverse effects (TRAEs) were leukopenia (50%), neutropenia (50%), and thrombocytopenia (41.7%). Fewer patients in the cohort (16.7%) had grade 3 or higher pneumonia.
In the older cohort, the most frequent grade 3 or higher TRAEs were leukopenia (50%), neutropenia (50%), and pneumonia (33.3%).
