https://orcid.org/0000-0002-3868-9267
Key Points
Patients with Waldenström macroglobulinemia and CXCR4 mutations have improved outcomes with ibrutinib + rituximab vs. ibrutinib monotherapy.
In patients with CXCR4 wild-type disease, adding rituximab to ibrutinib showed no clear additional benefit.
Ibrutinib monotherapy (I) and ibrutinib plus rituximab (I+R) are highly efficacious in treating Waldenström Macroglobulinemia (WM). However, the benefit of adding rituximab remains unclear, and a prospective trial to compare these two regimens has not been undertaken. Therefore, we performed a pooled analysis of prospective studies to compare their effectiveness. Patient-level demographic, response, and survival data were pooled from three prospective studies (NCT01614821, NCT02604511, NCT02165397). We included patients treated with I+R or I, excluding those without MYD88 mutations. Among 174 patients (58 I+R, 116 I), very good partial response (VGPR) rates were comparable across treatment groups (38% I+R vs. 28% I, p=0.21). The 48-month progression-free survival (PFS) rate was 74% with I+R versus 61% with I (p=0.22), and the 48-month overall survival (OS) rate was 94% versus 89% (p=0.45). In patients with CXCR4 mutations, I+R trended toward higher VGPR (27% vs. 11%; p=0.10) and had a superior 48‐month PFS rate (72% vs. 43%; p=0.03). CXCR4 mutations were associated with inferior VGPR (42% vs. 17%; p=0.001) and 48-month PFS in the I arm (43% vs. 72%; p=0.002). In the I+R arm, CXCR4 mutations were associated with numerically inferior VGPR (47% vs. 27%; p=0.12), but the 48-month PFS rate was not impacted (74% vs. 72%; p=0.96). I+R significantly improved PFS over I in patients with CXCR4-mutated WM, along with a non-significant increase in VGPR in this subgroup. These results support routine CXCR4 testing in patients with WM and clinical trials of rituximab with covalent or non‐covalent BTK inhibitors.
