Achieving a partial response (PR) or better at 6 months after ibrutinib initiation was predictive of prolonged progression-free survival (PFS) among patients with Waldenström macroglobulinemia (WM), according to results of a study published in the British Journal of Haematology.

Ibrutinib treatment results in durable responses among patients with symptomatic WM. Depth of response has been associated with PFS among patients treated with chemoimmunotherapy, but has not yet been evaluated as a surrogate for patients treated with ibrutinib. “We hypothesized that response depth is predictive of PFS in WM patients treated with ibrutinib,” the authors wrote.

The study comprised 2 cohorts: 93 patients from 2 different clinical trials in the learning cohort and 190 consecutive patients treated outside of a clinical trial in the validation cohort. All patients that had WM met the criteria for treatment and were treated with ibrutinib monotherapy.

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PR or better was achieved at 6 months by 64% of patients in the learning cohort and 71% of patients in the validation cohort.

In both cohorts, achieving PR or better at 6 months was significantly associated with better PFS at 3 years. In the learning cohort, the 3-year PFS was 81% in the group who achieved PR or better at 6 months compared with 57% in the group who did not achieve PR (P =.009). In the validation cohort, the 3-year PFS was 83% for those who achieved PR or better at 6 months compared with 54% among patients who did not achieve PR (P =.008).

There was no statistical difference in 3-year PFS among patients who achieved or did not achieve PR or better at 12 months in either cohort.

A multivariate analysis confirmed these results, demonstrating that achieving PR or better by 6 months was associated with prolonged PFS in both the learning (hazard ratio [HR], 0.38; P =.01) and the validation cohorts (HR, 0.18; P =.004).

The authors concluded that “attaining PR at 6 months on ibrutinib emerges as an intermediate outcome of interest and should be validated as surrogate for PFS in clinical trials evaluating Bruton tyrosine kinase inhibitors in WM.”

The authors cautioned, however, that the purpose of the study “was not to identify a timepoint in which ibrutinib therapy should be modified, and therefore not attaining PR or better at 6 months on ibrutinib monotherapy should not be factored into the decision of discontinuing or changing ibrutinib therapy.”

Disclosure: The authors of the original study disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original study.


Castillo JJ, Abeykoon JP, Gustine JN, et al. Partial response or better at six months is prognostic of superior progression-free survival in Waldenström macroglobulinaemia patients treated with ibrutinib. Br J Haematol. Published online November 18, 2020. doi: 10.1111/bjh.17225