OBJECTIVES:

Richter transformation (RT) is a significant but poorly understood and rarely analyzed complication of relapsed/refractory chronic lymphocytic leukemia (R/R CLL). The relative risk of RT during treatment with various therapeutic options, including novel targeted agents (BCL2 antagonists, BTK inhibitors, and PI3K inhibitors), has not yet been analyzed. Therefore, this study aimed to compare the risk of occurrence of RT between possible therapies for R/R CLL using statistical methods of Bayesian network meta-analysis (NMA).

METHODS:

An extensive systematic review was performed in medical databases (MEDLINE, Embase, and The Cochrane Library) and other sources to identify randomized clinical trials for R/R CLL (PROSPERO: CRD42022304330). Identified studies reporting RT rates in patients with R/R CLL were used for NMA. The results of NMA were presented as risk ratios (RR) with 95% credible intervals (CrI); SUCRA values were also calculated. Statistical analysis was performed in the R software using the GeMTC package.

RESULTS:

As a result of the systematic search, 5 studies reporting the frequency of RT were found and included in the NMA (ASCEND, MURANO, TUGELA, RESONATE, ELEVATE-RR). RT rates did not exceed 5% for all analyzed therapies (ACA, IDE+RTX, BEND+RTX, IBR, VEN+RTX, OFA, IDE+BEND+RTX). The NMA showed that the risk of RT was comparable between treatments, and no statistically significant differences were found.

CONCLUSIONS:

This study suggests that the choice of treatment regimen has no significant impact on the development of RT. The risk of RT is similar between chemoimmunotherapy, immunotherapy, and novel targeted therapies, including BTK and PI3K inhibitors and BCL-2 antagonists.