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. 2025 Jun 9;2(3):100128.
doi: 10.1016/j.bneo.2025.100128. eCollection 2025 Aug.

Real-world outcomes with ibrutinib in relapsed or refractory mantle cell lymphoma: a Danish population-based study

Trine Trab  1   2 , Iman Chanchiri  3   4 , Ahmed Ludvigsen Al-Mashhadi  5 , Emma Berggren Dall  5   6 , Stine Rasch  7 , Mette Johansen  8 , Simon Husby  1   2 , Mikkel Runason Simonsen  9   10 , Michael Roost Clausen  4 , Thomas Stauffer Larsen  3 , Jacob Haaber Christensen  3 , Robert Schou Pedersen  6 , Mikael Frederiksen  8 , Mats Jerkeman  11 , Christian Bjørn Poulsen  12 , Laura Mors Haunstrup  9 , Peter Brown  1 , Tarec Christoffer El-Galaly  5   13   14   15 , Kirsten Grønbæk  1   2   16
Affiliations

Real-world outcomes with ibrutinib in relapsed or refractory mantle cell lymphoma: a Danish population-based study

Trine Trab et al. Blood Neoplasia. .

Abstract

Ibrutinib was approved for relapsed/refractory (R/R) mantle cell lymphoma (MCL) based on high response rates in clinical trials, but it is unclear how effective ibrutinib is in the real-world setting. This study provides population-based response rates and survival estimates and characterization of prognostic indicators and adverse events (AEs) to ibrutinib for patients with R/R MCL. All patients diagnosed with MCL in Denmark from 2010 to 2022 were identified in the Danish Lymphoma Registry and screened for eligibility. Data were collected from health records. Patients receiving ibrutinib in second or later lines were included and followed from ibrutinib start until death or last follow-up. End points were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), frequency of AEs, and AE-related discontinuation and dose reductions. In total, 146 patients were included (median age, 73 years); 90 (62%) received ibrutinib in second line. ORR was 56%, median PFS 5.8 months, and median OS 12.0 months. In Cox regressions, factors associated with inferior PFS were Ki67 of ≥50% (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.47-3.71), blastoid or pleomorphic subtype (HR, 3.00; 95% CI, 2.04-4.41), early relapses (HR, 1.65; 95% CI, 1.15-2.36), and refractory disease (HR, 1.57; 95% CI, 1.07-2.30). Three-year cumulative incidences of discontinuation and dose reductions owing to AEs were 19% and 22%, respectively. Median OS after ibrutinib discontinuation was 1.9 months. In conclusion, real-world outcomes after initiation of ibrutinib for R/R MCL were poorer than observed in clinical trials, and dose-limiting toxicities were common, emphasizing the need for more effective treatments and dose-optimization studies.

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Conflict of interest statement

Conflict-of-interest disclosure: T.T. received research support from Janssen as funding paid to the institution; and travel support from Immedica Pharma. A.L.A.-M. received research funding from Genentech. P.B. was on the advisory board of Roche, AbbVie, Bristol Myers Squibb, and SERB. T.S.L. received research support from Genentech; was on the advisory board of Roche, Bristol Myers Squibb, and Gilead; and received travel support from Gilead and Roche. M.R.C. was on the advisory board of AbbVie, AstraZeneca, Genmab, Gilead, Incyte, Janssen, and Roche; and received travel support from AbbVie, AstraZeneca, Genmab, Janssen, Pfizer, and Roche. M. Jerkeman received research support from 10.13039/100004337Roche, 10.13039/100006483AbbVie, 10.13039/100004325AstraZeneca, and 10.13039/100002491Bristol Myers Squibb; and honoraria from Kite/10.13039/100005564Gilead, 10.13039/100004337Roche, AbbVie, Janssen, 10.13039/100004325AstraZeneca, and 10.13039/100002491Bristol Myers Squibb. K.G. received research support from Janssen as funding paid to the institution; and was a consultant for 10.13039/100019120Otsuka Pharma and GlaxoSmithKline. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Survival from the time of first ibrutinib initiation. (A) OS, (B) PFS, (C) OS stratified by 2L vs later-line ibrutinib use, and (D) PFS stratified by 2L vs later-line ibrutinib use.
Figure 2.
Figure 2.
PFS stratification. (A) POD24 from first-line therapy, (B) Ki67 categories (highest ever before ibrutinib), (C) morphological subtypes (blastoid or pleomorphic vs other), and (D) refractory disease to the latest line of therapy before ibrutinib.
Figure 3.
Figure 3.
OS after ibrutinib discontinuation. A) All cause discontinuation and B) stratified by reason for discontinuation (PD/no response versus other causes).
Figure 4.
Figure 4.
Cumulative incidence of discontinuation owing to AEs from the time of ibrutinib initiation with death and relapse after ibrutinib initiation as competing events.
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