First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab <i>versus</i> chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial

Abstract

iLLUMINATE is a randomized, open-label phase 3 study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or

Improved Therapy of B-Cell Non-Hodgkin Lymphoma by Obinutuzumab-Dianthin Conjugates in Combination with the Endosomal Escape Enhancer SO1861

“…For instance, 229 patients were included in a phase 3 study comparing obinutuzumab in combination with either chlorambucil or ibrutinib. At a median follow-up of 45 months, combination with ibrutinib significantly prolonged progression-free survival versus combination with chlorambucil (median not reached versus 22 months, p < 0.0001) [ 14 ].…”

The Role of Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions

“…In a subgroup analysis, patients with high-risk characteristics of CLL (del17p, del11q, TP53 mutations, or unmutated IgHV) also showed significant improvement in PFS in the ibrutinib arm compared to immunochemotherapy (median NR vs. 14.7 months; p < 0.001). The recently published results from the final analysis, with a median follow-up of 45 months [8], confirmed that the combination of ibrutinib with obinutuzumab is an effective chemotherapy-free regimen, and that is associated with a lower risk of disease progression compared to chlorambucil and obinutuzumab in patients with high-risk disease. Therapy was well tolerated, and no new safety issues were observed.…”

“…BTK inhibitors (BTKis) have become very important targets in the treatment of inflammatory reactions and autoimmune diseases, as well as of B-cell malignancies, including CLL. These agents have transformed CLL management in both previously untreated and relapsed/refractory patients [7][8][9][10][11][12]. BTK inhibitors are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors (Table 1) [13].…”

Management of front line chronic lymphocytic leukemia

“…Hence, the addition of this anti-CD20 antibody to ibrutinib does not seem to improve outcome either, although the second trial excluded patients with del17p. [37][38][39] In light of these data, the addition of an anti-CD20 antibody to ibrutinib does not lead to additional efficacy and therefore would not be recommended.…”

“…36 Patients with del17p or mutTP53 achieved an estimated 48-month PFS rate of 74% while patients without del17p or mutTP53 were at 77% within the final analysis of the ILLU-MINATE trial. 37 Within the CLL14 trial, patients with del17p/mutTP53 had a significantly longer median PFS of 49.0 months when treated with venetoclax-obinutuzumab versus chlorambucil-obinutuzumab with 20.8 months. 54 If retreatment with venetoclax-obinutuzumab would be an option for patients with progressive disease is currently being investigated within the ReVenG trial (NCT04895436).…”