Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: Updated results of the CLL8 trial

Blood

Volumn 127, Issue 2, 2016, Pages 208-215

  Fischer, Kirsten ^a   Bahlo, Jasmin ^a   Fink, Anna Maria ^a   Goede, Valentin ^a   Herling, Carmen Diana ^a   Cramer, Paula ^a   Langerbeins, Petra ^a   Von Tresckow, Julia ^a   Engelke, Anja ^a   Maurer, Christian ^a   Kovacs, Gabor ^a   Herling, Marco ^a   Tausch, Eugen ^b   Kreuzer, Karl Anton ^a   Eichhorst, Barbara ^a   Böttcher, Sebastian ^c   Seymour, John F ^d   Ghia, Paolo ^e   Marlton, Paula ^f,g   Kneba, Michael ^c   Wendtner, Clemens Martin ^a,h   Döhner, Hartmut ^b   Stilgenbauer, Stephan ^b   Hallek, Michael ^a   more..

^a UNIVERSITY OF COLOGNE   (Germany)

^b UNIVERSITY OF ULM   (Germany)

^c UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e SAN RAFFAELE HOSPITAL   (Italy)

^f PRINCESS ALEXANDRA HOSPITAL   (Australia)

^g UNIVERSITY OF QUEENSLAND   (Australia)

^h Klinikum Schwabing   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPHOSPHAMIDE; FLUDARABINE; RITUXIMAB; ANTINEOPLASTIC AGENT; VIDARABINE;

ADULT; AGED; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER PATIENT; CANCER SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; CONFERENCE PAPER; CYTOGENETICS; DRUG EFFICACY; DRUG SAFETY; FEMALE; FOLLOW UP; HUMAN; LEUKEMIA REMISSION; MAJOR CLINICAL STUDY; MALE; NEUTROPENIA; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); ADVERSE EFFECTS; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; CONTROLLED STUDY; DISEASE FREE SURVIVAL; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MIDDLE AGED; MULTICENTER STUDY; MULTIMODALITY CANCER THERAPY; PHASE 3 CLINICAL TRIAL; PROCEDURES; RANDOMIZED CONTROLLED TRIAL; REMISSION; TREATMENT OUTCOME; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; COMBINED MODALITY THERAPY; CYCLOPHOSPHAMIDE; DISEASE-FREE SURVIVAL; FEMALE; FOLLOW-UP STUDIES; HUMANS; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MIDDLE AGED; REMISSION INDUCTION; RITUXIMAB; TREATMENT OUTCOME; VIDARABINE;

EID: 84955482904     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2015-06-651125     Document Type: Conference Paper

References (32)

1. Dreger P. Allotransplantation for chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2009;2009:602-609.
2. Hallek M, Fischer K, Fingerle-Rowson G, et al; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: A randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164-1174.
3. Fischer K, Cramer P, Busch R, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: A multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2012;30(26): 3209-3216.
4. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-1110.
5. Foon KA, Boyiadzis M, Land SR, et al. Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009;27(4): 498-503.
6. Byrd JC, Brown JR, O'Brien S, et al; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223.
7. Farooqui MZ, Valdez J, Martyr S, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: A phase 2, single-arm trial. Lancet Oncol. 2015;16(2):169-176.
8. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014; 370(11):997-1007.
9. Brown JR, Byrd JC, Coutre SE, et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110d, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014;123(22):3390-3397.
10. Burger JA, Keating MJ, Wierda WG, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: A single-arm, phase 2 study. Lancet Oncol. 2014; 15(10):1090-1099.
11. Zenz T, Eichhorst B, Busch R, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28(29):4473-4479.
12. Souers AJ, Leverson JD, Boghaert ER, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19(2):202-208.
13. O'Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: An open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15(1):48-58.
14. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48(1):198-206.
15. Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87(12):4990-4997.
16. Extermann M, Overcash J, Lyman GH, Parr J, Balducci L. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol. 1998;16(4):1582-1587.
17. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000; 343(26):1910-1916.
18. Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. [see comments] Blood. 1999;94(6): 1840-1847.
19. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. [see comments] Blood. 1999;94(6):1848-1854.
20. Strati P, Wierda W, Burger J, et al. Myelosuppression after frontline fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: Analysis of persistent and new-onset cytopenia. Cancer. 2013;119(21):3805-3811.
21. Gill S, Carney D, Ritchie D, et al. The frequency, manifestations, and duration of prolonged cytopenias after first-line fludarabine combination chemotherapy. Ann Oncol. 2010;21(2):331-334.
22. Tam CS, O'Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112(4): 975-980.
23. Woyach JA, Ruppert AS, Heerema NA, et al. Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712. J Clin Oncol. 2011;29(10):1349-1355.
24. Langerbeins P, Maurer C, Bahlo J, et al. Second primary malignancies in chronic lymphocytic leukemia: A metaanalysis of four prospective trials of the German CLL Study Group. Hematol Oncol. 2013;31(Suppl 1). Abstract 108.
25. Ghia EM, Jain S, Widhopf GF II, et al. Use of IGHV3-21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post-germinal center leukemogenic selection. Blood. 2008;111(10): 5101-5108.
26. Pflug N, Bahlo J, Shanafelt TD, et al. Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood. 2014;124(1):49-62.
27. Rassenti LZ, Jain S, Keating MJ, et al. Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia. Blood. 2008; 112(5):1923-1930.
28. Stilgenbauer S, Schnaiter A, Paschka P, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014;123(21):3247-3254.
29. Hallek M, Wanders L, Ostwald M, et al. Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. Leuk Lymphoma. 1996;22(5-6): 439-447.
30. Hamblin TJ, Orchard JA, Ibbotson RE, et al. CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood. 2002;99(3):1023-1029.
31. Bottcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: A multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol. 2012;30(9):980-988.
32. Hallek M. Signaling the end of chronic lymphocytic leukemia: new frontline treatment strategies. Blood. 2013;122(23):3723-3734.