Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real‐world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR)

• Published in: British journal of haematology Vol. 202; no. 1; pp. 40 - 47
• Main Authors: Špaček, Martin, Smolej, Lukáš, Šimkovič, Martin, Nekvindová, Lucie, Křístková, Zlatuše, Brychtová, Yvona, Panovská, Anna, Mašlejová, Stanislava, Bezděková, Lucie, Écsiová, Dominika, Vodárek, Pavel, Zuchnická, Jana, Mihályová, Jana, Urbanová, Renata, Turcsányi, Peter, Lysák, Daniel, Novák, Jan, Brejcha, Martin, Líkařová, Tereza, Vodička, Prokop, Baranová, Jana, Trněný, Marek, Doubek, Michael
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.07.2023
• Subjects: Aged; chronic lymphocytic leukaemia; Chronic lymphocytic leukemia; Clinical trials; Enzyme inhibitors; Hematology; Humans; ibrutinib; idelalisib; Karyotypes; Kinases; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Multivariate analysis; p53 Protein; Protein-tyrosine kinase; real‐world evidence; Recurrence; Registries; Retrospective Studies; Rituximab; Survival; Toxicity; ibrutinib; chronic lymphocytic leukaemia; real-world evidence; idelalisib; rituximab
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.18736

Summary Idelalisib (idela), a phosphatidylinositol 3‐kinase inhibitor, and ibrutinib, a Bruton tyrosine kinase inhibitor, were the first oral targeted agents approved for relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). However, no randomised trials of idelalisib plus rituximab (R‐idela) versus ibrutinib have been conducted. Therefore, we performed a real‐world retrospective analysis of patients with R/R CLL treated with R‐idela (n = 171) or ibrutinib (n = 244). The median age was 70 versus 69 years, with a median of two previous lines. There was a trend towards higher tumour protein p53 (TP53) aberrations and complex karyotype in the R‐idela group (53% vs. 44%, p = 0.093; 57% vs. 46%, p = 0.083). The median progression‐free survival (PFS) was significantly longer with ibrutinib (40.5 vs. 22.0 months; p < 0.001); similarly to overall survival (OS; median 54.4 vs. 37.7 months, p = 0.04). In multivariate analysis, only PFS but not OS remained significantly different between the two agents. The most common reasons for treatment discontinuation included toxicity (R‐idela, 39.8%; ibrutinib, 22.5%) and CLL progression (27.5% vs. 11.1%). In conclusion, our data show significantly better efficacy and tolerability of ibrutinib over R‐idela in patients with R/R CLL treated in routine practice. The R‐idela regimen may still be considered a reasonable option in highly selected patients without a suitable treatment alternative.