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Regression of oral proliferative leukoplakia following initiation of ibrutinib therapy in two allogeneic hematopoietic stem cell transplant recipients

Bone Marrow Transplantation volume 55, pages 1844–1846 (2020)Cite this article

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Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) affecting the oral cavity in 45–83% of cases [1]. Secondary oral malignancy, which can be preceded by oral precancerous lesions such as leukoplakia, is a serious and potentially fatal late complication of allo-HSCT that has been associated with duration and severity of cGVHD [2,3,4]. Proliferative leukoplakia (PL) is a slow-growing yet aggressive subset of oral leukoplakia with a high malignant transformation rate to oral squamous cell carcinoma, that is characterized by a frequently multifocal appearance, including but not limited to nodular and verrucous features [5]. Although there is available data reporting the effectiveness of several treatment options, management approaches of PL have not demonstrated consistent effectiveness with lesions typically recurring after treatment, and without reducing the rate of malignant transformation [6]. Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor as well as inhibitor of the interleukin-2-inducible T-cell kinase (ITK), that is FDA approved for several hematologic malignancies including CLL, as well as for refractory cGVHD [7]. We herein report two allo-HSCT recipients with extensive oral PL with regression of oral lesions after initiating Ibrutinib therapy.

A 53-year-old male with a history of myelodysplastic syndrome/acute myeloid leukemia, 9 months after myeloablative allo-HSCT with cGVHD of the oral cavity (managed with topical steroids), skin, myofascial/joints and eyes, presented with new onset of diffuse white hyperkeratotic changes with focal demarcated plaque-like lesions on the maxillary and mandibular facial gingiva, hard palate mucosa, and mandibular lingual gingiva (Fig. 1c). Over a period of 4–5 years, PL progressed showing well-demarcated thick diffuse hyperkeratotic changes on upper and lower gingiva, hard palate mucosa and tongue dorsum. Incisional biopsy demonstrated hyperkeratosis without evidence of epithelial dysplasia. Five years after initial presentation of the PL, the patient started ibrutinib 420 mg daily for the management of systemic cGVHD, which was subsequently discontinued within 3 months for unmanageable side effects (memory loss, lack of balance, and fatigue) and not resumed. At the latest follow-up, 3 months after discontinuing ibrutinib, oral examination demonstrated a remarkable regression of the PL (Fig. 1d).

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Fig. 1

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Authors and Affiliations

  1. Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital, Boston, MA, USA

    Paolo J. Fantozzi & Nathaniel Treister

  2. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA

    Paolo J. Fantozzi & Nathaniel Treister

  3. Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA

    Alessandro Villa

  4. Department of Medical Oncology, Dana Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA, USA

    Joseph H. Antin

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Correspondence to Paolo J. Fantozzi.

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Fantozzi, P.J., Villa, A., Antin, J.H. et al. Regression of oral proliferative leukoplakia following initiation of ibrutinib therapy in two allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant 55, 1844–1846 (2020). https://doi.org/10.1038/s41409-020-0889-2

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