Rituximab, cladribine, and cyclophosphamide (RCC) induction with rituximab maintenance in chronic lymphocytic leukemia: PALG - CLL4 (ML21283) trial

Eur J Haematol. 2018 May;100(5):465-474. doi: 10.1111/ejh.13042. Epub 2018 Mar 22.

Abstract

Objectives: PALG CLL4 is the first, randomized, phase IIIb study with rituximab, cladribine, and cyclophosphamide (RCC) induction and subsequent maintenance with rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients.

Methods: The induction treatment consisted of 6 RCC cycles regimen. Patients with complete response (CR) or partial response (PR) after an induction phase were randomized into a maintenance arm with rituximab or an observational arm.

Results: In the intention-to-treat population, 97 patients completed the induction phase with an overall response rate (ORR) of 73.2% (CR 22.7%, PR 50.5%). Subsequently, 66 patients were randomized into the rituximab maintenance arm (n = 33) or the observational arm (n = 33). CR rates were 57.1% in the maintenance group vs 50% in the observational group. PFS was significantly longer in the rituximab maintenance vs the observational arm (P = .028). The multivariate Cox model indicated that del17p (P = .006) and elevated beta-2-microglobulin (P = .015) significantly increased the hazard ratio (HR) of progression, whereas the presence of CD38 (P = .013) significantly decreased it; maintenance therapy with rituximab (P < .0001) significantly decreased the HR of disease progression.

Conclusions: The study confirmed the high efficacy and acceptable safety profile of induction therapy with RCC and maintenance therapy with rituximab in previously untreated patients with CLL.

Keywords: RCC regimen; chronic lymphocytic leukemia; first line; maintenance; rituximab.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers
  • Cladribine / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Female
  • Humans
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Maintenance Chemotherapy
  • Male
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Remission Induction
  • Rituximab / administration & dosage
  • Treatment Outcome

Substances

  • Biomarkers
  • Cladribine
  • Rituximab
  • Cyclophosphamide