Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial

The Lancet Haematology

Volumn 3, Issue 7, 2016, Pages e317-e329

  Greil, Richard ^a,b,c   Obrtlíková, Petra ^d   Smolej, Lukáš ^e   Kozák, Tomáš ^f   Steurer, Michael ^g   Andel, Johannes ^h   Burgstaller, Sonja ⁱ   Mikušková, Eva ^j   Gercheva, Liana ^k   Nösslinger, Thomas ^l   Papajík, Tomáš ^m   Ladická, Miriam ^j   Girschikofsky, Michael ⁿ   Hrubiško, Mikuláš ^o   Jäger, Ulrich ^p   Fridrik, Michael ^q   Pecherstorfer, Martin ^r   Králiková, Eva ^s   Burcoveanu, Cristina ^t   Spasov, Emil ^u   Petzer, Andreas ^v   Mihaylov, Georgi ^w   Raynov, Julian ^x   Oexle, Horst ^y   Zabernigg, August ^z   Flochová, Emília ^aa   Palášthy, Stanislav ^ab   Stehlíková, Olga ^ac   Doubek, Michael ^ac   Altenhofer, Petra ^b,c   Pleyer, Lisa ^a,b,c   Melchardt, Thomas ^a,b,c   Klingler, Anton ^ad   Mayer, Jiří ^ac   Egle, Alexander ^a,b,c   more..

^a PARACELSUS MEDICAL UNIVERSITY   (Austria)

^b Salzburg Cancer Research Institute   (Austria)

^c Cancer Cluster Salzburg   (Austria)

^d CHARLES UNIVERSITY   (Czech Republic)

^e CHARLES UNIVERSITY   (Czech Republic)

^f CHARLES UNIVERSITY   (Czech Republic)

^g INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^h Abteilung für Innere Medizin III   (Austria)

ⁱ Klinikum Wels Grieskirchen GmbH   (Austria)

^j CANCER RESEARCH INSTITUTE   (Slovakia)

^k UNIVERSITY HOSPITAL ST MARINA   (Bulgaria)

^l HANUSCH HOSPITAL   (Austria)

^m UNIVERSITY HOSPITAL OLOMOUC   (Czech Republic)

ⁿ St Elisabethinen Krankenhaus   (Austria)

^o SLOVAK MEDICAL UNIVERSITY   (Slovakia)

^p MEDICAL UNIVERSITY OF VIENNA   (Austria)

^q KEPLER UNIVERSITY HOSPITAL   (Austria)

^r Universitätsklinikum Tulln Karl Landsteiner Privatuniversität für Gesundheitswissenschaften   (Austria)

^s Fakultna nemocnica s poliklinikou FD Roosevelta Banska Bystrica   (Slovakia)

^t Regional Institute of Oncology   (Romania)

^u MEDICAL UNIVERSITY OF PLOVDIV   (Bulgaria)

^v Krankenhaus der Barmherzigen Schwestern Linz   (Austria)

^w NSHATHD   (Bulgaria)

^x MILITARY MEDICAL ACADEMY   (Bulgaria)

^y Klinik Innere Medizin 4   (Austria)

^z Innere Medizin II   (Austria)

^aa Martinska Fakultna Nemocnica   (Slovakia)

^ab J A Reimana ^*  (Slovakia)

^ac MASARYK UNIVERSITY   (Czech Republic)

^ad ASSIGN DATA MANAGEMENT AND BIOSTATISTICS GMBH   (Austria)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BENDAMUSTINE; CD38 ANTIGEN; CYCLOPHOSPHAMIDE; FLUDARABINE; IMMUNOGLOBULIN G; LENALIDOMIDE; OFATUMUMAB; RITUXIMAB; ANTINEOPLASTIC AGENT; VIDARABINE;

ADULT; AGED; ARTICLE; BLOOD TOXICITY; BONE MARROW BIOPSY; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION; GENE MUTATION; HUMAN; HUMAN TISSUE; LEUKEMIA REMISSION; LOWER RESPIRATORY TRACT INFECTION; MAINTENANCE THERAPY; MAJOR CLINICAL STUDY; MALE; MINIMAL RESIDUAL DISEASE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; OPEN STUDY; PHASE 3 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION; VERY ELDERLY; ANALOGS AND DERIVATIVES; CANCER STAGING; CLINICAL TRIAL; COMPARATIVE STUDY; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MIDDLE AGED; PATHOLOGY; PATHOPHYSIOLOGY; REMISSION; SURVIVAL RATE;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENDAMUSTINE HYDROCHLORIDE; CYCLOPHOSPHAMIDE; FEMALE; HUMANS; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MIDDLE AGED; NEOPLASM STAGING; REMISSION INDUCTION; RITUXIMAB; SURVIVAL RATE; VIDARABINE;

EID: 84991702543     PISSN: None     EISSN: 23523026     Source Type: Journal    
DOI: 10.1016/S2352-3026(16)30045-X     Document Type: Article

References (35)

1. 1 Hallek, M, Cheson, BD, Catovsky, D, et al. 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 111 (2008), 5446–5456.
2. 2 Nabhan, C, Rosen, ST, Chronic lymphocytic leukemia: a clinical review. JAMA 312 (2014), 2265–2276.
3. 3 Hallek, M, Chronic lymphocytic leukemia: 2013 update on diagnosis, risk stratification and treatment. Am J Hematol 88 (2013), 803–816.
4. 4 Keating, MJ, O'Brien, S, Albitar, M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 23 (2005), 4079–4088.
5. 5 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 112 (2008), 975–980.
6. 6 Hallek, M, Fischer, K, Fingerle-Rowson, G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 376 (2010), 1164–1174.
7. 7 Robak, T, Dmoszynska, A, Solal-Celigny, P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 28 (2010), 1756–1765.
8. 8 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 27 (2009), 498–503.
9. 9 Fischer, K, Cramer, P, Stilgenbauer, S, et al. Bendamustine combined with rituximab (BR) in first-line therapy of advanced CLL: a multicenter phase II trial of the German CLL Study Group (GCLLSG). ASH Annual Meeting Abstracts, 114, 2009, 205 (abstr).
10. 10 Thompson, PA, Wierda, WG, Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL. Blood 127 (2016), 279–286.
11. 11 McClanahan, F, Gribben, J, Transplantation in chronic lymphocytic leukemia: does it still matter in the era of novel targeted therapies?. Hematol Oncol Clin North Am 28 (2014), 1055–1071.
12. 12 Bosch, F, Abrisqueta, P, Villamor, N, et al. Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia. J Clin Oncol 27 (2009), 4578–4584.
13. 13 Van Oers, MHJ, Van Glabbeke, M, Baila, L, et al. Rituximab maintenance treatment of relapsed/resistant follicular non-hodgkin's lymphoma: long-term outcome of the EORTC 20981 Phase III Randomized Intergroup Study. ASH Annual Meeting Abstracts, 112, 2008, 836 (abstr).
14. 14 Vidal, L, Gafter-Gvili, A, Leibovici, L, et al. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst 101 (2009), 248–255.
15. 15 Del Poeta, G, Del Principe, MI, Buccisano, F, et al. Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia. Cancer 112 (2008), 119–128.
16. 16 Egle, A, Weiss, L, Melchardt, T, et al. Final analysis of induction treatment with fludarabine, cyclophosphamide plus rituximab (FCR) followed by fludarabine plus rituximab (FR) and remission maintenance therapy with rituximab in previously untreated B-chronic lymphocytic leukemia (B-CLL): the Chairos AGMT CLL4/Roche ML18434 study. ASH Annual Meeting Abstracts, 116, 2010, 1380 (abstr).
17. 17 Rawstron, AC, Villamor, N, Ritgen, M, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 21 (2007), 956–964.
18. 18 Boettcher, 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 30 (2012), 980–988.
19. 19 Zenz, T, Mertens, D, Kuppers, R, Dohner, H, Stilgenbauer, S, From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 10 (2010), 37–50.
20. 20 Griffin, MM, Morley, N, Rituximab in the treatment of non-Hodgkin's lymphoma—a critical evaluation of randomized controlled trials. Expert Opin Biol Ther 13 (2013), 803–811.
21. 21 Salles, G, Seymour, JF, Offner, F, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 377 (2011), 42–51.
22. 22 Robak, T, Maintenance in CLL. Blood 122 (2013), 3854–3855.
23. 23 Foa, R, Del Giudice, I, Cuneo, A, et al. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients. Am J Hematol 89 (2014), 480–486.
24. 24 Pleyer, L, Egle, A, Hartmann, TN, Greil, R, Molecular and cellular mechanisms of CLL: novel therapeutic approaches. Nat Rev Clin Oncol 6 (2009), 405–418.
25. 25 Lin, K, Tam, CS, Keating, MJ, et al. Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens. Blood 113 (2009), 3168–3171.
26. 26 Byrd, JC, Brown, JR, O'Brien, S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 371 (2014), 213–223.
27. 27 Furman, RR, Sharman, JP, Coutre, SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 370 (2014), 997–1007.
28. 28 Moreton, P, Kennedy, B, Lucas, G, et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol 23 (2005), 2971–2979.
29. 29 Santacruz, R, Villamor, N, Aymerich, M, et al. The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy. Haematologica 99 (2014), 873–880.
30. 30 EMA (CHMP). Guideline on the use of minimal residual disease as an endpoint in chronic lymphocytic leukaemia studies. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/12/WC500179047.pdf (accessed March 14, 2016).
31. 31 Food and Drug Administration. Public workshop on minimal residual disease (MRD) as a surrogate endpoint in chronic lymphocytic leukemia (CLL). http://www.fda.gov/Drugs/NewsEvents/ucm340707.htm (accessed March 14, 2016).
32. 32 Hamblin, AD, Hamblin, TJ, The immunodeficiency of chronic lymphocytic leukaemia. Br Med Bull 87 (2008), 49–62.
33. 33 Abrisqueta, P, Villamor, N, Terol, MJ, et al. Rituximab maintenance after first-line therapy with rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) for chronic lymphocytic leukemia. Blood 122 (2013), 3951–3959.
34. 34 Wendtner, CM, Ritgen, M, Schweighofer, CD, et al. Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission—experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia 18 (2004), 1093–1101.
35. 35 van Oers, MH, Kuliczkowski, K, Smolej, L, et al. Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study. Lancet Oncol 16 (2015), 1370–1379.