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. 2014 Jun;3(3):555-64.
doi: 10.1002/cam4.226. Epub 2014 Mar 19.

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

Antonio Cuneo  1 , Francesco Cavazzini, Maria Ciccone, Giulia Daghia, Olga Sofritti, Elena Saccenti, Massimo Negrini, Gian Matteo Rigolin
Affiliations

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

Antonio Cuneo et al. Cancer Med. 2014 Jun.

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.

Keywords: BCL2; Chronic lymphocytic leukemia; chemoimmunotherapy; genetic lesions; tyrosine-targeted treatment.

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Figures

Figure 1
Figure 1
Improved 10-year survival in different age groups. Survival is expressed as ratio of absolute survival of CLL patients divided by the expected survival of a comparable group of persons in the general population. Data from (A) Brenner et al. and (B) the Swedish registry . CLL, chronic lymphocytic leukemia.
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