Study Identifies Prognostic Factors for Richter’s Transformation in Ibrutinib-Treated CLL

Certain characteristics are associated with the development of Richter’s transformation in patients with chronic lymphocytic leukemia (CLL) who receive ibrutinib treatment, according to a recent analysis.

Adam S Kittai, MD, of the Ohio State University, and colleagues conducted the research because Richter’s transformation has a “dismal prognosis” and there are “limited data evaluating risk of [Richter’s transformation] in patients treated with ibrutinib.”

Dr. Kittai and colleagues conducted a retrospective analysis to identify prognostic variables associated with Richter’s transformation and overall survival (OS) at progression after ibrutinib treatment. They identified 559 patients with CLL who received ibrutinib between 2010 and 2019 and included 179 patients who progressed on ibrutinib at a median follow-up of 44.5 months since initiating treatment.

Of the 179 patients, 30.2% developed Richter’s transformation after a median follow-up of 20.8 months from progression.

The median OS was four months from the date of Richter’s transformation, “suggesting that the prognosis for [Richter’s transformation] remains poor,” Dr. Kittai and colleagues wrote.

Dr. Kittai and colleagues determined progression on treatment (hazard ratio [HR], 4.01; P=.003), higher lactate dehydrogenase (HR for two-fold increase, 1.80; P=.0001), and lymphadenopathy without lymphocytosis (HR, 2.88; P=.02) were all independent prognostic variables for developing Richter’s transformation at progression.

“Progression with lymphadenopathy without lymphocytosis continued to be an independent prognostic variable of worse OS post-progression,” Dr. Kittai and colleagues wrote.

The researchers also conducted a subset analysis of 50 patients who received a positron emission tomography-computed tomography scan at disease progression. The median maximum standardized uptake value was 15.2 in patients who would develop Richter’s transformation, while it was 7.7 in those who did not (P=.0030).

“A lymph node biopsy to rule out [Richter’s transformation] should be considered in patients who received ibrutinib who progress on treatment, have an elevated [lactate dehydrogenase level], or progress with lymphadenopathy without lymphocytosis,” Dr. Kittai and colleagues concluded.

Reference

Kittai AS, Huang Y, Beckwith KA, et al. Patient characteristics that predict Richter’s transformation in patients with chronic lymphocytic leukemia treated with ibrutinib. Am J Hematol. 2023;98(1):56-65.