Modern treatment in chronic lymphocytic leukemia: impact on survival and efficacy in high‐risk subgroups

Abstract

Treatment of chronic lymphocytic leukemia (CLL) has dramatically changed over the last years, with significant improvement in overall survival (OS) and increased efficacy in genetically defined “high-risk” disease. Besides prospective clinical trials usually enrolling young and fit patients, retrospective studies were performed comparing the outcome of patients belonging to different age groups and showing longer survival in patients diagnosed in the most recent periods. In patients younger than 70 years the 10-year relative survival was 43–53% in the 1980s as compared with 59–63% in the 2000s. Likewise, the 10-year relative survival in patients >70 years was 22–42% in the 1980s and 46–55% in the 2000s. Improved outcome derived in part by the introduction of effective regimens in genetically defined “high-risk” disease (i.e., 17p−, 11q−, TP53, NOTCH1, SF3B1 mutations), especially in the younger and/or fit patients. The unfavorable prognostic significance of 11q− was overcome by chemoimmunotherapy. High-dose steroids with anti-CD52 appeared to improve the response rate in 17p-/TP53 mutated cases and allogeneic transplantation achieved prolonged disease control irrespective of high-risk disease. Further improvement is being generated by the new anti-CD20 obinutuzumab in the elderly and by mechanism-based treatment using kinase-targeting agents or anti-BCL2 molecules yielding high-response rate and impressive progression-free survival in the chemorefractory setting as well as in previously untreated patients.

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia: Clinical and biologic correlations

“…In conclusion, this study suggests that conventional karyotyping with DSP30/IL2 stimulation in CLL patients is more effective than FISH for the detection of KA allowing for a more precise refinement of the prognostic risk. This may have important clinical implications in the definition of a risk‐adapted strategy for monitoring and treating CLL patients (Cuneo et al, ; Foà et al, ) prompting the inclusion of conventional karyotyping in the screening of CLL patient, as routinely performed in other hematologic disorders (Rigolin and Cuneo, ).…”

Gender and ethnic differences in incidence and survival of lymphoid neoplasm subtypes in anAsian population: Secular trends of a population‐based cancer registry from 1998 to 2012

“…We have reasons to support this too. First, there has been evidence to demonstrate the recent advancements in therapeutics (such as rituximab, interferon, thalidomide, bortezomib, lenalidomide, chlorambucil, fludarabine and alemtuzumab) for the treatment of mature B‐cell lymphomas namely follicular lymphoma, large B‐cell lymphoma, plasma cell neoplasm, CLL/SLL and marginal zone lymphoma, including their associations with improved survival for these patients. These drugs are widely used in both the public and private hospitals of Singapore as shown by the national sales volume data from 2007 to 2013 (rituximab: 17,230 vials in public hospitals and 19,673 vials in private hospitals; bortezomib: 4,657 vials in public hospitals and 2,255 vials in private hospitals; alemtuzumab: 186 vials in public hospitals and 90 vials in private hospitals) .…”

Real‐world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres

“…Considerable advances have been made in our understanding of the biology of CLL and use of prognostic markers to predict disease progression and therapeutic outcomes. Although diagnostic and prognostic testing is recommended (Hallek et al , ; National Comprehensive Cancer Network, ; https://www.nccn.org/), interpretation of international guidelines still varies considerably, specifically regarding when to initiate CLL therapy, how to apply prognostic factors when making treatment choices, and the type and sequence of therapeutic regimen offered to patients (Hallek, ; Cuneo et al , ; Mertens & Stilgenbauer, ). Although the results of testing for immunoglobulin heavy chain locus ( IGHV ) and fluorescence in situ hybridization (FISH) have been shown to predict survival in patients with CLL (Parikh et al , ) they are not recommended to be used to drive treatment initiation decisions (Hallek et al , ).…”