TOPLINE:

Adding rituximab to ibrutinib therapy significantly improved 48-month progression-free survival in patients with Waldenström macroglobulinemia (WM) who had CXCR4 mutations, boosting rates from 43% to 72%. The combination showed particular promise in this genetic subgroup, while maintaining comparable overall survival rates of 94% vs 89% in the broader WM population.

METHODOLOGY:

• Researchers conducted a pooled analysis of 174 patients (58 received ibrutinib plus rituximab and 116 received ibrutinib monotherapy) from three prospective studies.
• Patient-level demographic, response, and survival data were collected from trials NCT01614821 (63 relapsed/refractory WM patients on ibrutinib), NCT02604511 (30 treatment-naive patients on ibrutinib), and NCT02165397 (including ibrutinib plus rituximab arm).
• Analysis excluded patients without MYD88 mutations (n = 25) and those treated with rituximab monotherapy (n = 75).
• Responses were assessed using modified consensus criteria from the sixth International Workshop on Waldenström Macroglobulinemia.

TAKEAWAY:

• Very good partial response rates were comparable between treatment groups at 38% for ibrutinib plus rituximab vs 28% for ibrutinib monotherapy (P = .21).
• In patients with CXCR4 mutations, ibrutinib plus rituximab demonstrated superior 48-month progression-free survival rate of 72% vs 43% with ibrutinib monotherapy (P = .03).
• CXCR4 mutations were associated with inferior very good partial response rates (17% vs 42%; P = .001) and 48-month progression-free survival in the ibrutinib monotherapy arm (43% vs 72%; P = .002).
• The 48-month overall survival rates were similar between groups at 94% for ibrutinib plus rituximab vs 89% for ibrutinib monotherapy (P = .45).

IN PRACTICE:

“Our results show that rituximab provides additional benefits in patients with WM and CXCR4 mutations. Adding rituximab to zanubrutinib could also improve outcomes in this patient subgroup. Thus, the combination of BTK inhibitors plus rituximab is a particularly interesting approach for patients with CXCR4-mutated disease, and it should be evaluated in prospective clinical trials,” wrote the authors of the study.

SOURCE:

This study was led by Alberto Guijosa and Jorge J. Castillo, Dana-Farber Cancer Institute in Boston. It was published online in Blood Advances.

LIMITATIONS:

According to the authors, the pooled design introduced significant variations in follow-up durations across studies, which is important given the potential for response deepening over time. The lack of formal randomization increased the risk for selection bias and may have contributed to imbalances in baseline characteristics such as prior treatment status. Additionally, differences in MYD88 and CXCR4 testing methodologies between studies and limitations in available pooled data prevented adjustment for key prognostic markers such as lactate dehydrogenase and albumin.

DISCLOSURES:

Shayna Sarosiek disclosed ties with ADC Therapeutics, BeiGene Inc., and Cellectar Biosciences. Steven P. Treon reported relationships with AbbVie/Pharmacyclics, Janssen, BeiGene Inc., Eli Lilly, Bristol Myers Squibb, and Ono Pharmaceuticals, and is a named inventor of MYD88 and CXCR4 testing for WM. Castillo disclosed ties with AbbVie, AstraZeneca, BeiGene Inc., Cellectar, Johnson & Johnson, Loxo, Mustang Bio, Nurix, and Pharmacyclics. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.