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Ibrutinib Interruption in CLL: Pseudo-transformation or True Richter Transformation?

By: Justine Landin, PhD
Posted: Wednesday, October 28, 2020

Dose interruption of Bruton’s tyrosine kinase inhibitor ibrutinib may transiently alter tumor morphology in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In a recent study by Qing Chen, MD, of Northwestern University Feinberg School of Medicine, Chicago, and colleagues, ibrutinib's discontinuation led to a pseudo-transformation of tumors that resembled enhanced disease pathology. Still, subsequent reinstatement of the medication resolved these clinical manifestations. This work was published in the British Journal of Haematology.

“Caution should be taken to distinguish pseudo-transformation from true Richter transformation in the era of targeted therapy,” the study authors stated. “While conventional Richter transformation requires aggressive immunochemotherapy, pseudo-transformation may be simply and effectively treated by resuming ibrutinib therapy.”

The retrospective study included one female and four male patients, with a median age of 70 years, who had Rai stages of disease ranging from I to IV. These patients had all previously received single-agent ibrutinib therapy and had achieved a partial response with disease control. Due to surgery or acute infection, ibrutinib therapy was paused for a median of 14 days. Following ibrutinib interruption, all patients exhibited signs of disease progression, such as increased lymphadenopathy, lymphocytosis, anemia, and B symptoms.

Lymph nodes were biopsied 7 to 13 days following ibrutinib disruption. These biopsies indicated that morphologic adaptations suggest Richter transformation, such as diffuse infiltrate of large atypical lymphocytes, increased (80%–90%) proliferation rates, and enhanced lactate dehydrogenase (LDH) levels. Based on these analyses, patients were diagnosed with diffuse large B-cell lymphoma. However, following the reinstatement of ibrutinib, LDH levels returned to normal levels within 4 weeks, and cytopenias were improved. Between 1 and 6 months following ibrutinib resumption, lymphadenopathy was decreased, and there was no longer evidence of diffuse large B-cell lymphoma. At the follow-up time of 3 to 22 months, all patients were alive and continuing ibrutinib treatment.

Disclosure: For full disclosures of the study authors, see wiley.com.



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