Nivolumab Plus BTK Inhibitor Ibrutinib Demonstrates Activity, Safety Among Patients With DLBCL Richter Transformation

According to findings from a phase 2 study recently published in Blood Advances, the combination of nivolumab and Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib is an active and safe regimen for patients with diffuse large B-cell lymphoma (DLBCL) Richter transformation (RT), a rare complication of chronic lymphocytic leukemia (CLL) with poor outcomes. 

Nitin Jain, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors explained that despite treatment improvements for CLL, “about 2% to 10% of patients with CLL develop a diffuse large B-cell lymphoma transformation over the duration of their CLL diagnosis, known as Richter transformation, resulting in median overall survival (OS) of less than 12 months.” 

The upregulation of the PD-1/PD-L1 signaling pathway is a contributing factor in immune evasion, which is common in patients with RT. Dr Jain et al aimed to investigate the value of combining nivolumab, a PD-1 blocking antibody, with ibrutinib, a BTK inhibitor, among patients with DLBCL RT. Additionally, the study also included a cohort of patients with CLL, which was closed early due to slow accrual as well as the existing availability of novel therapeutic agents for those patients. 

In this study, patients were included who were at least 18 years of age or older and had adequate liver and renal function. The patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of 24 cycles. A standard dose of ibrutinib was initiated from cycle 2 onward, and continued daily until progression. For those patients who were already on ibrutinib, the same was continued while nivolumab was initiated. 

A total of 24 patients with DLBCL RT were enrolled. Within this group, 10 patients (42%) had received prior treatment for RT and 13 patients (54%) had received a prior BTK inhibitor. A total of 10 patients (42%) responded with a median duration of response of 15 months. The median overall survival was 13 months. Notably, 4 of the 24 patients had checkpoint inhibition–related immunological toxicities. In the CLL cohort, 10 patients were enrolled, of whom 3 patients converted from partial to complete remission; while 1 patient had a grade 2 immunological toxicity.

In the cohort of heavily pretreated patients with DLBCL RT, study authors noted an encouraging overall response rate of 42% with combined nivolumab plus ibrutinib. Dr Jain and coauthors concluded, “Combined nivolumab and ibrutinib is an active and safe regimen for patients with DLBCL RT.”

“Given the limited treatment options for patients with RT, checkpoint inhibition provides a potential therapeutic option for these patients,” they added. 

Source: 

Jain N, Senapati J, Thakral B, et al; A phase 2 study of nivolumab combined with ibrutinib in patients with diffuse large B-cell Richter transformation of CLL. Blood Adv 2023; 7 (10) doi: 10.1182/bloodadvances.2022008790