Long‐term outcomes of second‐line versus later‐line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis

BACKGROUND: We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second‐line versus later‐line. Here, we present an updated pooled analysis with a longer follow‐up of 35.2 months. METHODS: Data were pooled from two studies—BGB‐3111‐AU‐003 (NCT02343120) and BGB‐3111‐206 (NCT03206970) of zanubrutinib in R/R MCL. The patients were divided into two groups based on the treatment line of zanubrutinib: the second‐line and the later‐line group. The inverse propensity score weighting method was used to balance the baseline covariates between the groups. The primary outcome was overall survival (OS). Secondary outcomes included progression‐free survival (PFS), PFS, and OS rates, objective response rate (ORR), duration of response (DOR), and safety. RESULTS: Among 112 pooled patients, 41 (36.6%) patients received zanubrutinib as second‐line and 71 (63.4%) patients as later‐line therapy. After weighting, OS was significantly improved in the second‐line versus later‐line group (HR, 0.459 [95% CI: 0.215, 0.98]; p = 0.044) with median OS not estimable in both groups. The PFS was similar between the two groups (HR, 0.78 [95% CI: 0.443, 1.373]; p = 0.389) but with numerically longer median PFS in the second‐line versus later‐line group (27.8 vs. 22.1 months). ORR was numerically higher in the second‐line versus later‐line (88.6% vs. 85.7%), and DOR was similar between the two groups (25.2 vs. 25.1 months). Zanubrutinib showed a similar safety profile in both groups. CONCLUSION: Zanubrutinib in second‐line treatment was associated with significantly improved OS compared with later‐line treatment of R/R MCL.