title: The long-term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years.
abstract: With 10+ years follow-up in the Leukaemia Research Fund (LRF) CLL4 trial, we report the effect of salvage therapy, and the clinical/biological features of the 10-year survivors treated for chronic lymphocytic leukaemia (CLL). Overall survival (OS) was similar in the three randomized arms. With fludarabine-plus-cyclophosphamide (FC), progression-free survival (PFS) was significantly longer (P < 0.0001), but OS after progression significantly shorter, than in the chlorambucil or fludarabine arms (P < 0.0001). 614/777 patients progressed; 524 received second-line and 260 third-line therapy, with significantly better complete remission (CR) rates compared to first-line in the chlorambucil arm (7% vs. 13% after second-, 18% after third-line), but worse in the FC arm (38% vs. 15% after both second and third-line). OS 10 years after progression was better after a second-line CR versus a partial response (36% vs. 16%) and better with FC-based second-line therapy (including rituximab in 20%) or a stem cell transplant (28%) versus all other treatments (10%, P < 0.0001). The 176 (24%) 10-year survivors tended to be aged <70 years, with a "good risk" prognostic profile, stage A-progressive, achieving at least one CR, with a first-line PFS >3 years and receiving ≤2 lines of treatment. In conclusion, clinical/biological features and salvage treatments both influence the long-term outcome. Second-line therapies that induce a CR can improve OS in CLL patients.
authors.affiliation: Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
authors.forename: Monica
authors.initials: M
authors.lastname: Else
authors.affiliation: Clinical Trial Service Unit, Oxford, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wade
authors.affiliation: Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, UK.
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.affiliation: Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002699:Chlorambucil / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002699:Chlorambucil; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Chronic lymphocytic leukaemia, CLL; clinical trials; prognostic factors; salvage therapy; survival