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, investigator-initiated study (NCT05506410) presented at the
Among patients with previously untreated MCL younger than 65 years (n = 12), the overall response rate (ORR) and complete response (CR) rate 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 aged 65 to 75 years (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; the 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.
The trial investigators sought to evaluate the efficacy and safety of zanubrutinib treatment regimens in patients with previously untreated MCL.
The open-label, multicenter study enrolled patients aged at least 18 years 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 1 measurable lesion, normal heart function, and kidney function defined as serum creatinine of at least 1.5 times the upper level of normal.
If patients had definite neuropathy or psychosis, had participated in clinical trials 4 weeks prior to enrollment, or had systemic autoimmune disease or primary or secondary central tumors, they were not included in the trial.
Patients in the younger cohort received zanubrutinib 160 mg twice daily, a 375-mg/m² dose of rituximab on day 0, bendamustine 70 mg/m² on days 1 and 2, cytarabine 400 mg/m² on days 1 to 3, and prednisone 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 70 mg/m² on day 0, cytarabine 300 mg/m² on days 1 to 3, and prednisone 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 four 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, and 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) in the older cohort. Moreover, most patients in the younger cohort were male (66.7%) compared with half in the older cohort (50%).
High- or intermediate-high–risk disease, as defined by the simplified Mantle Cell Lymphoma International Prognostic Index score, was more common in the older cohort (50%) than in 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; additionally, 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%).
