Real-world data on efficacy and safety of obinutuzumab plus chlorambucil, rituximab plus chlorambucil, and rituximab plus bendamustine in the frontline treatment of chronic lymphocytic leukemia: The GO-CLLEAR Study by the Czech CLL Study Group
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Observational Study
Grant support
NA
Czech CLL Study Group
Czech Leukemia Study Group
ML41010
F. Hoffmann-La Roche
MH CZ-RVO 65269705
Ministerstvo Zdravotnictví Ceské Republiky
LQ1601
Ministry of Education, Youth and Sport, CR project NPUII CEITEC 2020
Q28/LF1
Charles University Prague
Q40/08
Charles University Prague
PubMed
32400885
DOI
10.1002/hon.2744
Knihovny.cz E-resources
- Keywords
- CIRS, CLL, frontline treatment, obinutuzumab-chlorambucil, rituximab-bendamustine, rituximab-chlorambucil,
- MeSH
- Bendamustine Hydrochloride administration & dosage MeSH
- Chlorambucil administration & dosage MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell drug therapy pathology MeSH
- Antibodies, Monoclonal, Humanized administration & dosage MeSH
- Remission Induction MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Retrospective Studies MeSH
- Rituximab administration & dosage MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Names of Substances
- Bendamustine Hydrochloride MeSH
- Chlorambucil MeSH
- Antibodies, Monoclonal, Humanized MeSH
- obinutuzumab MeSH Browser
- Rituximab MeSH
Until recently, a combination of anti-CD20 antibody plus less intensive chemotherapy was a standard of care in elderly population with previously untreated chronic lymphocytic leukemia (CLL). The aim of this observational study was to retrospectively assess efficacy and safety of obinutuzumab + chlorambucil (G-Clb), rituximab + chlorambucil (R-Clb), and bendamustine + rituximab (BR) given as the frontline therapy within routine practice. The final analyzed dataset included 398 consecutive CLL patients from 10 hematology centers cooperating within the Czech CLL Study Group: 63 treated with G-Clb, 78 with R-Clb, and 257 with BR. There were no significant differences in prognostic and predictive markers among the groups. On the contrary, median age at the start of therapy and cumulative illness rating scale (CIRS) score was significantly higher in R-Clb group. Obinutuzumab plus chlorambucil regimen was preferably offered to elderly patients (compared to BR) with less severe comorbidities and lower CIRS score (compared to R-Clb). A time period when a treatment was indicated had also a strong impact on the choice of the regimen. The overall response rate reached 76% (30% complete remissions, CRs) in G-Clb, 75% (22% CRs) in R-Clb, and 85% (47% CRs) in BR group. Median event-free survival was 49.0 months for G-Clb, 20.3 months for R-Clb, and 37.0 months for BR group. Neutropenia grade ≥ 3 developed in 43% of G-Clb, 31% of R-Clb and in 49% of BR patients, grade ≥ 3 infections were recorded in 17% of G-Clb, 6.4% of R-Clb, and 17% of BR patients. In conclusion, real-world therapeutic activity of G-Clb appears to be at least comparable to prospective clinical trial data. R-Clb yields relatively good results in very old and severely comorbid patients.
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Hematology and Oncology University Hospital Plzeň Czech Republic
Department of Hematology Havirov Hospital and Polyclinic Havířov Czech Republic
Department of Hematology Hospital Pelhřimov Pelhřimov Czech Republic
Department of Hematology University Hospital Ostrava Czech Republic
Department of Hematooncology University Hospital Olomouc Czech Republic
Institute of Biostatistics and Analyses Ltd Brno Czech Republic
See more in PubMed
Hallek M. Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2017;92(9):946-965. https://doi.org/10.1002/ajh.24826.
National Cancer Institute [Website]. Surveillance epidemiology and end results cancer statistics review. 2009. http://seer.cancer.gov/statfacts/html/clyl.html. Accessed September 5, 2017.
Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v78-v84. https://doi.org/10.1093/annonc/mdv303.
Panovska A, Doubek M, Brychtova Y, Mayer J. Chronic lymphocytic leukemia and focusing on epidemiology and management in everyday hematologic practice: recent data from the Czech Leukemia Study Group for Life (CELL). Clin Lymphoma Myeloma Leuk. 2010;10(4):297-300. https://doi.org/10.1111/ejh.12106.
O'Reilly A, Murphy J, Rawe S, Garvey M. Chronic lymphocytic leukemia: a review of front-line treatment options, with a focus on elderly CLL patients. Clin Lymphoma Myeloma Leuk. 2018;18(4):249-256. https://doi.org/10.1016/j.clml.2018.02.003.
Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG. Chronic lymphocytic leukaemia. Nat Rev Dis Primers. 2017;3:17008. http://doi.org/10.1038/nrdp.2017.8.
Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127(2):208-215. https://doi.org/10.1182/blood-2015-06-651125.
Hallek M, Cheson BD, Catovsky D, Caligaris-cappio F, Dighiero G, Do H. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12):5446-5456. https://doi.org/10.1182/blood-2007-06-093906.
Goede V, Fischer K, Engelke A, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370:1101-1110. https://doi.org/10.1056/NEJMoa1313984.
Michallet AS, Aktan M, Hiddemann W, et al. Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study. Haematologica. 2018;103(4):698-706. https://doi.org/10.3324/haematol.2017.170480.
Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. https://doi.org/10.1056/NEJMoa1815281.
Eichhorst B, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic, leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17(7):928-942. https://doi.org/10.1016/S1470-2045(16)30051-1.
Špaček M, Obrtlíková P, Hrobková S, et al. Prospective observational study in comorbid patients with chronic lymphocytic leukemia receiving first-line bendamustine with rituximab. Leuk Res. 2019;79:17-21. https://doi.org/10.1016/j.leukres.2019.02.002.
Rawstron AC, Fazi C, Agathangelidis A, et al. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study. Leukemia. 2016;30(4):929-936. https://doi.org/10.1038/leu.2015.313.
Sharman JP, Banerji V, Fogliatto LM, et al. ELEVATE TN: phase 3 study of acalabrutinib combined with obinutuzumab (O) or alone vs O plus chlorambucil (Clb) in patients (Pts) with treatment-naïve chronic lymphocytic leukemia (CLL). Blood. 2019;134(Supplement_1):31. https://doi.org/10.1182/blood-2019-128404.
Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43-56. https://doi.org/10.1016/S1470-2045(18)30788-5.
