Ibrutinib Plus Lenalidomide and Rituximab Among Patients With R/R DLBCL

Results from a Phase 2 Trial

According to findings from a phase 2 study recently published in The Lancet: eClinical Medicine, ibrutinib, a BTK inhibitor, plus lenalidomide and rituximab demonstrated antitumor activity with durable responses among patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Dr Radhakrishnan Ramchandren, MD, University of Tennessee Health Science Center, Knoxville, Tennessee, and coauthors stated as the impetus for this study that, “Patients with relapsed/refractory DLBCL have poor outcomes, particularly those ineligible for stem cell transplantation (SCT), with life expectancy of a few months and overall survival (OS) rates of 28% at 1 year and 20% at 2 years.”

They added that although researchers of previous studies have observed an unsafe safety profile in ibrutinib, a combination of ibrutinib, lenalidomide, and rituximab “could prove beneficial in patients with more aggressive lymphomas such as DLBCL, especially in the relapsed/refractory setting, where few treatment options are available.” 

Dr Ramchandren et al aimed to assess a primary endpoint of overall response rate (ORR), as well as secondary endpoints including duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. 

89 patients with a median age of 64 years and who had R/R DLBCL were enrolled in this multicenter study. All patients received treatment over 6 cycles of 28 days. They were administered ibrutinib at 560 mg once daily, along with lenalidomide at 20 mg or 25 mg once daily on days 1 to 21 of each cycle, and rituximab at 375 mg/m2 on day 1 of each cycle. Patients received this combination of treatments until disease progression or toxicity was observed. 

Results indicated that the best ORR was 49%, with the ORR of patients who received 20 mg vs 25 mg of lenalidomide being 53% vs 44%. 28% of all patients (n=24) achieved CR. The median PFS was 5.4 months, the median OS was 14.2 months, and the median DOR was 38.3 months. 

In terms of safety, grade 3 or 4 adverse events were observed in 91% of patients (n=81), with the most frequently occurring events being neutropenia (40%), maculopapular rash (18%), anemia (13%), and diarrhea (10%). Serious adverse events were observed in 64% of all patients, and fatal adverse events were observed in 13%, with causes including worsened DLBCL (n=7), pneumonia (n=3), sepsis (n=1), and cardiac arrest (n=1). 

As all endpoints were met, Dr Ramchandren et al concluded “the combination of ibrutinib, lenalidomide, and rituximab demonstrated encouraging antitumour activity with durable responses and a manageable safety profile in patients with relapsed/refractory non-GCB DLBCL ineligible for [stem cell transplant].” 

They added that although the original study didn’t have an endpoint of comparing 2 doses of lenalidomide, “phase 1b data suggested that doses >15 mg lenalidomide demonstrated higher response rates.” 

Source: 

Ramchandren R, Johnson P, Ghosh N, et al. The iR2 regimen (ibrutinib plus lenalidomide and rituximab) for relapsed/refractory DLBCL: a multicentre, non-randomised, open-label phase 2 study. The Lancet eClinicalMedicine. 2023;56. doi:https://doi.org/10.1016/j.eclinm.2022.101779