Study Finds Slightly Lower Risk of Richter Transformation for Patients With Chronic Lymphocytic Leukemia in the “Novel Agent Era”

Patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) who were treated in the “novel agent era” (defined as the time following the FDA approval of ibrutinib for CLL in February 2014) may have a lower risk of Richter transformation (RT) compared with patients treated before such an era.

Richter transformation, also known as Richter syndrome, is a serious complication of CLL relating to the transformation of CLL/SLL into an aggressive form of lymphoma, generally diffuse large B-cell lymphoma.

Researchers set out to determine whether the incidences of RT in newly diagnosed and treated CLL differ in the era of novel agents compared with past treatments in what they call the “pre-novel agent era.”

The researchers used the Mayo Clinic CLL database to identify patients with previously untreated CLL/SLL who were seen within 12 months of diagnosis between January 2000 and April 2023 (n = 3347). At diagnosis, the median age of the full cohort was 65 years, and 66% of the patients were men. The median follow-up for the entire cohort was 5.6 years. The median follow-ups for those in the pre-novel agent era (n = 1981) was 9.5 years and 3.2 years for the novel agent era cohort (n = 1366).

A total of 82 patients were diagnosed with RT, with similar baseline patient characteristics at the time of CLL and RT diagnoses between those diagnosed before the novel agent era (n = 69) and during the novel agent era (n = 13).

“Using Cox regression analysis, we compared the incidence of RT, both after initial CLL diagnosis and after initiation of CLL therapy, between patients diagnosed with CLL in the pre-novel agent era versus the novel agent era,” the authors wrote in their study.

The results showed a slight difference in the RT incidence from time of CLL/SLL diagnosis between the pre-novel agent and novel agent era patients, but the difference was not statistically significant (hazard ratio [HR] = 1.6; [95% CI, 0.9 to 3.0], p = 0.13).

Among the 1981 patients diagnosed with CLL/SLL in the pre-novel agent era, the 1- and 5-year incidence rates for RT from the time of diagnosis were 0.6% (95% CI; 0.4% to 1.1%) and 2.1% (95% CI, 1.5% to 2.8%), respectively. Among the 1366 patients diagnosed with CLL/SLL in the novel agent era, the 1- and 5-year incidence rates following CLL/SLL diagnosis were 0.5% (95% CI, 0.2 to 1.1%) and 1.1% (95% CI, 0.6% to 2.2%), respectively.

Patients treated for CLL/SLL in the pre-novel agent era (n = 926) had 1-year RT incidence rates of 0.3% (95% CI; 0.1% to 1.0%), while those treated in the novel agent era (n = 456) had 1-year incidence rates of 0.2% (95% CI, 0.0 to 1.8%). The 5-year incidence rates for these groups were 3.7% (95% CI; 2.6% to 5.2%) and 1.9% (95% CI, 0.7% to 5.0%), respectively. Although the results indicated that there was an increased risk of RT after CLL/SLL directed therapy in the pre-novel agent versus the novel agent era, the difference did not reach statistical significance (HR = 2.4 [95% CI, 0.9 to 6.1], p = 0.07).

The authors noted that one of the limitations of this study was limited follow-up, and that more studies are needed on this subject. Still, the results indicated that those treated in the novel agent era, may have a slightly lower risk of RT compared with those treated in the pre-novel agent era.

“Patients who received CLL/SLL directed treatment appear to have a lower risk of RT in the novel agent era,” the authors concluded. “This may be driven by the fact that none of the patients who developed RT in the novel agent era received chemoimmunotherapy. Whether novel agent use for CLL/SLL suppresses the development of RT or avoids the risk associated with cytotoxic chemotherapy-induced clonal evolution requires further study.”

Reference:
Hampel PJ, Rabe KG, Wang W, et al. Incidence of Richter transformation in patients with chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL): a cohort study evaluating different therapeutic eras. Presented at: 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA. https://ash.confex.com/ash/2023/webprogram/Paper185076.html