Second Primary Malignancies in Patients With B-Cell Lymphomas Treated With Bruton's Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis.

Cuiping Ma, Yuexia Lu, Jiahang Li, Wenjing Liu, Jie Liu

Abstract readSystematic ReviewMeta-Analysis

In one paragraph

Synthesis in European journal of haematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Cuiping MaOncology Department, Guang'anmen Hospital China Academy of Chinese Medical Sciences, Beijing, China.

Yuexia LuOncology Department, Guang'anmen Hospital China Academy of Chinese Medical Sciences, Beijing, China.

Jiahang LiOncology Department, Guang'anmen Hospital China Academy of Chinese Medical Sciences, Beijing, China.

Wenjing LiuOncology Department, Guang'anmen Hospital China Academy of Chinese Medical Sciences, Beijing, China.

Jie LiuOncology Department, Guang'anmen Hospital China Academy of Chinese Medical Sciences, Beijing, China.ORCID https://orcid.org/0000-0002-6112-2947

Funding

project of Hangzhou Institute of Medicine, Chinese Academy of Sciences 2024ZZBS10Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences CI2021A05502

6 · The paper itself

Abstract

objectiveTo evaluate the overall second primary malignancy (SPM) burden in patients with B-cell lymphomas treated with Bruton's tyrosine kinase (BTK) inhibitors and compare SPM risk versus non-BTK inhibitor or placebo controls.

methodsWe searched major databases from inception to September 30, 2025. The primary outcome was SPM incidence. Consistent treatment backgrounds were defined as comparable baseline clinical and treatment characteristics, with BTK inhibitor exposure as the main between-arm difference.

resultsFifty-two studies involving 9337 patients were included, mainly CLL/SLL; MCL was the largest non-CLL/SLL subtype. Pooled SPM incidence was 8% (95% CI: 6%-11%) with a median follow-up of 31.5 months. Multivariable meta-regression identified follow-up duration as the only independent predictor, whereas disease subtype, inhibitor generation, prior therapy lines, study design, and age were not significant. Furthermore, SPM patterns were comparable between CLL/SLL and non-CLL/SLL cohorts. Compared with controls, BTK inhibitors did not significantly increase SPM risk (RR = 1.30, 95% CI: 0.95-1.78), a finding confirmed in analyses with consistent treatment backgrounds (RR = 1.03, 95% CI: 0.85-1.25).

conclusionsSPMs occur across disease backgrounds and are mainly influenced by follow-up duration. Current evidence does not establish a direct carcinogenic effect of BTK inhibitors.

Indexed as

Agammaglobulinaemia Tyrosine KinaseLymphoma, B-CellNeoplasms, Second PrimaryProtein Kinase InhibitorsHumansIncidenceAgammaglobulinaemia Tyrosine KinaseBTK protein, humanProtein Kinase InhibitorsB‐cell lymphomaBruton's tyrosine kinase inhibitorschronic lymphocytic leukemiameta‐analysissecond primary malignancies

Identifiers

PMID42289275

DOI10.1111/ejh.70235

PMCPMC13542850

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