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The long‐term outcome of patients in the LRF CLL 4 trial: the effect of salvage treatment and biological markers in those surviving 10 years
Author(s) -
Else Monica,
Wade Rachel,
Oscier David,
Catovsky Daniel
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13824
Subject(s) - fludarabine , medicine , chlorambucil , rituximab , salvage therapy , oncology , cyclophosphamide , progression free survival , chronic lymphocytic leukemia , surgery , gastroenterology , chemotherapy , leukemia , lymphoma
Summary With 10+ years follow‐up in the Leukaemia Research Fund (LRF) CLL 4 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.