Abstract: PS1191

Type: Poster Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 17:30 - 19:00

Location: Poster area

Background

Ibrutinib is active in previously-treated Waldenstrom’s Macroglobulinemia (WM). MYD88 and CXCR4 mutations impact ibrutinib response. We report on the first prospective study of ibrutinib monotherapy in symptomatic, untreated WM patients, and impact of CXCR4 mutation status on outcome.

Aims
To evaluate ibrutinib monotherapy in symptomatic, treatment-naive WM patients. Primary study endpoint was assessment of overall and major response rates. Secondary endpoints included assessment of safety, and impact of MYD88 and CXCR4 tumor mutation status on response outcome.

Methods
Ibrutinib (420 mg) was administered daily until progression or unacceptable toxicity. Dose reduction was permitted for toxicity. All patient tumors were genotyped for MYD88 and CXCR4. 

Results

30 WM patients received ibrutinib. All carried MYD88 mutation, and 14 (47%) CXCR4 mutation. Following ibrutinib, median serum IgM levels declined from 4,370 to 1,513 mg/dL; bone marrow involvement declined from 65% to 20%; and hemoglobin rose from 10.3 to 13.9 g/dL (p<0.0001 for all comparisons). Overall (> minor) and major (> partial) responses for all patients were 100% and 83%, respectively. Major (94% vs. 71%) and very good partial (31 vs. 7%) responses were higher, and time to major responses more rapid (1.8 vs. 7.3 months; p=0.01) in wild-type versus mutated CXCR4 patients, respectively.  With a median follow-up of 14.6 months, two patients (both CXCR4 mutated) progressed. The 18-month estimated progression-free survival for all patients is 92% (95% CI 73-98%). All patients are alive. Grade 2/3 treatment-related toxicities in >5% of patients included arthralgia (7%), bruising (7%), neutropenia (7%), URTI (7%), UTI (7%), atrial fibrillation (10%), and hypertension (13%).  There was no grade 4, or unexpected toxicities.

Conclusion

Ibrutinib is highly active, produces durable responses, and is safe as primary therapy in symptomatic WM patients. CXCR4 mutation status impacts responses to ibrutinib.

Session topic: 20. Indolent Non-Hodgkin lymphoma – Clinical

Keyword(s): Mutation status, Waldenstrom's macroglobulinemia, ibrutinib