Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) to a more aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). Traditional anthracycline- or platinum-based chemotherapy is associated with complete response rates of less than 20 percent, and median survival after transformation is less than 12 months. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, has shown significant efficacy in relapsed/refractory CLL.
Mayo Clinic researchers, first author Sameer Parikh, M.B.B.S., conducted a study in Blood to determine the efficacy of ibrutinib in the treament of richter syndrome. They assessed the characteristics of four CLL patients who developed biopsy-proven DLBCL.
Because of a lack of efficacious standard treatment options for refractory RS, ibrutinib was initiated in three of the patients. The fourth patient, with heavily pretreated CLL harboring a 17p deletion, was felt to be a poor candidate for anthracycline-based therapy and began treatment with ibrutinib at the time of RS diagnosis.
The median duration of ibrutinib therapy for these patients was 6.1 months. All patients experienced an improvement in constitutional symptoms. According to the 2007 revised response criteria for malignant lymphoma, one patient had a CR and two patients had a partial response. The fourth patient was started on low-dose ibrutinib because of concomitant voriconazole use, he subsequently died of pulmonary mucormycosis which was diagnosed prior to ibrutinib initiation.
The patient who achieved a CR is currently receiving ibrutinib (duration of therapy, 2.8 months). Of the two patients who achieved a partial response, one experienced progression of CLL after 11 months and the other experienced progression of DLBCL after eight months of ibrutinib therapy.
Although the progression-free survival in these four patients was relatively short, it was encouraging for a condition with a median survival of less than 12 months. The study's results suggests that ibrutinib has potential as a novel therapeutic approach for patients with RS, and future trials investigating its use, either as monotherapy or in combination, appear warranted.