Ibrutinib resistance in a patient with transformed diffuse large B-cell lymphoma from primary pulmonary mucosa-associated lymphoid tissue lymphoma

ABSTRACT

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is rare among lung neoplasia cases, representing only 0.5%–1% of newly diagnosed primary lung lymphoma. MALT lymphoma with relapsed refractory and malignant transformation is highly heterogeneous and consensus therapy remains undetermined. We report a 55 year-old woman with a 3 year history of primary pulmonary MALT lymphoma confined to the lung presenting with massive pleural effusion. After two cycles of R-CHOP and six cycles of R2-CHOP, pleural effusion disappeared but the pulmonary mass remained persistent. Second-line therapies R2-GemOx failed to make any substantial improvement. Core-needle puncture biopsy of the pulmonary mass was obtained and pathological testing revealed transformed diffuse large B-cell lymphoma of germinal center B-cell subtype. Next-generation sequencing confirmed BN2 subtype. The mass showed no reduction after three cycles of R-MINE, following which the BTK inhibitor ibrutinib was administered to this patient. Unfortunately, after two months of ibrutinib treatment, the patient rapidly developed an enlarged mass and hyperprogressive disease, to which she subsequently succumbed.

KEYWORDS:

• Mucosa-associated lymphoid tissue lymphoma
• pleural effusion
• BN2 subtype
• Ibrutinib resistance

Acknowledgments

We thank Professors Jianyong Li and Wei Xu at Jiangsu Province Hospital in Nanjing for their generous help. We thank Gillian Campbell, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Disclosure of Potential Conflicts of Interest

The authors declare no conflicts of interest.

Ethics approval and consent to participate

The enrolled patient provided written informed consent.

Additional information

Funding

This study was funded by the National Natural Science Foundation international cooperation (81570184), the Science and Technology Project of Nantong City (MS22018008), the Science and Technology Project of Nantong City (MS12017003-2), China Postdoctoral Science Foundation (2019M660127), Jiangsu Province Postdoctoral Science Foundation (2019K062), Jiangsu Province Postdoctoral Foundation (2019Z146).