Abstract
Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL. © 2014 John Wiley & Sons Ltd.
| Original language | English |
|---|---|
| Pages (from-to) | 466-477 |
| Number of pages | 12 |
| Journal | British Journal of Haematology |
| Volume | 167 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2014 |
Bibliographical note
Cited By :27Export Date: 3 October 2022
CODEN: BJHEA
Correspondence Address: Awan, F.T.; Division of Hematology, B 307 Starling Loving Hall, 320 W. 10th Avenue, United States
Chemicals/CAS: cyclophosphamide, 50-18-0; fludarabine, 21679-14-1; lumiliximab, 357613-86-6; rituximab, 174722-31-7; vidarabine, 2006-02-2, 5536-17-4; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Cyclophosphamide; fludarabine; lumiliximab; rituximab; Vidarabine
Funding details: National Institutes of Health, NIH
Funding details: National Cancer Institute, NCI, P30CA016672
References: Byrd, J.C., O'Brien, S., Flinn, I.W., Kipps, T.J., Weiss, M., Rai, K., Lin, T.S., Harris, S., Phase 1 study of lumiliximab with detailed pharmacokinetic and pharmacodynamic measurements in patients with relapsed or refractory chronic lymphocytic leukemia (2007) Clinical Cancer Research, 13, pp. 4448-4455; Byrd, J.C., Kipps, T.J., Flinn, I.W., Castro, J., Lin, T.S., Wierda, W., Heerema, N., O'Brien, S., Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia (2010) Blood, 115, pp. 489-495; Caligaris-Cappio, F., Hamblin, T.J., B-cell chronic lymphocytic leukemia: a bird of a different feather (1999) Journal of Clinical Oncology, 17, pp. 399-408; Cheson, B.D., Bennett, J.M., Grever, M., Kay, N., Keating, M.J., O'Brien, S., Rai, K.R., National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment (1996) Blood, 87, pp. 4990-4997; Christian, B.A., Lin, T.S., Antibody therapy for chronic lymphocytic leukemia (2008) Seminars in Hematology, 45, pp. 95-103; Eichhorst, B., Fink, A.-M., Busch, R., Lange, E., Wendtner, C., Stilgenbauer, S., Hallek, M., Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) versus Bendamustine and Rituximab (BR) in Previously Untreated and Physically Fit Patients (pts) with Advanced Chronic Lymphocytic Leukemia (CLL): results of a planned interim analysis of the CLL10 Trial, An International, Randomized Study of the German CLL Study Group (GCLLSG) (2013) Blood (ASH Annual Meeting Abstracts), 122, p. 526; Fischer, K., Cramer, P., Busch, R., Bottcher, S., Bahlo, J., Schubert, J., Pfluger, K.H., Wendtner, C.M., 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 (2012) Journal of Clinical Oncology, 30, pp. 3209-3216; Fournier, S., Delespesse, G., Rubio, M., Biron, G., Sarfati, M., CD23 antigen regulation and signaling in chronic lymphocytic leukemia (1992) The Journal of Clinical Investigation, 89, pp. 1312-1321; Gordon, J., Cairns, J.A., Liu, Y.J., Flores-Romo, L., MacLennan, I.C., Jansen, K.U., Bonnefoy, J.Y., Role of membrane and soluble CD23 in lymphocyte physiology (1991) Monographs in Allergy, 29, pp. 156-168; Hallek, M., Fischer, K., Fingerle-Rowson, G., Fink, A.M., Busch, R., Mayer, J., Hensel, M., Stilgenbauer, S., Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial (2010) Lancet, 376, pp. 1164-1174; (2009), http://www.meddra.org/sites/default/files/guidance/file/smq_intguide_12_0_english.pdf, Introductory Guide for Standardised Medical Dictionary for Regulatory Activities (MedDRA@) terminology Queries (SMQs) Version 12.0; Keating, M.J., O'Brien, S., Albitar, M., Lerner, S., Plunkett, W., Giles, F., Andreeff, M., Kantarjian, H., Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia (2005) Journal of Clinical Oncology, 23, pp. 4079-4088; Kijimoto-Ochiai, S., CD23 (the low-affinity IgE receptor) as a C-type lectin: a multidomain and multifunctional molecule (2002) Cellular and Molecular Life Sciences, 59, pp. 648-664; Kijimoto-Ochiai, S., Noguchi, A., Ohnishi, T., Araki, Y., Complex formation of CD23/surface immunoglobulin and CD23/CD81/MHC class II on an EBV-transformed human B cell line and inferable role of tetraspanin (2004) Microbiology and Immunology, 48, pp. 417-426; Lampert, I.A., Wotherspoon, A., Van Noorden, S., Hasserjian, R.P., High expression of CD23 in the proliferation centers of chronic lymphocytic leukemia in lymph nodes and spleen (1999) Human Pathology, 30, pp. 648-654; Liu, Y.J., Cairns, J.A., Holder, M.J., Abbot, S.D., Jansen, K.U., Bonnefoy, J.Y., Gordon, J., MacLennan, I.C., Recombinant 25-kDa CD23 and interleukin 1 alpha promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis (1991) European Journal of Immunology, 21, pp. 1107-1114; Lopez-Matas, M., Rodriguez-Justo, M., Morilla, R., Catovsky, D., Matutes, E., Quantitative expression of CD23 and its ligand CD21 in chronic lymphocytic leukemia (2000) Haematologica, 85, pp. 1140-1145; Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P., Toxicity and response criteria of the Eastern Cooperative Oncology Group (1982) American Journal of Clinical Oncology, 5, pp. 649-655; Pathan, N.I., Chu, P., Hariharan, K., Cheney, C., Molina, A., Byrd, J., Mediation of apoptosis by and antitumor activity of lumiliximab in chronic lymphocytic leukemia cells and CD23+ lymphoma cell lines (2008) Blood, 111, pp. 1594-1602; Reichert, J.M., Technology evaluation: lumiliximab, Biogen Idec (2004) Current Opinion in Molecular Therapeutics, 6, pp. 675-683; Robak, T., Novel monoclonal antibodies for the treatment of chronic lymphocytic leukemia (2008) Current Cancer Drug Targets, 8, pp. 156-171; Robak, T., Dmoszynska, A., Solal-Celigny, P., Warzocha, K., Loscertales, J., Catalano, J., Afanasiev, B.V., Moiseev, S.I., Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia (2010) Journal of Clinical Oncology, 28, pp. 1756-1765; Sarfati, M., Chevret, S., Chastang, C., Biron, G., Stryckmans, P., Delespesse, G., Binet, J.L., Bron, D., Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia (1996) Blood, 88, pp. 4259-4264; Strati, P., Wierda, W., Burger, J., Ferrajoli, A., Tam, C., Lerner, S., Keating, M.J., O'Brien, S., Myelosuppression after frontline fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: analysis of persistent and new-onset cytopenia (2013) Cancer, 119, pp. 3805-3811; Tam, C.S., Wolf, M., Prince, H.M., Januszewicz, E.H., Westerman, D., Lin, K.I., Carney, D., Seymour, J.F., Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma (2006) Cancer, 106, pp. 2412-2420; Tam, C.S., O'Brien, S., Wierda, W., Kantarjian, H., Wen, S., Do, K.A., Thomas, D.A., Keating, M.J., Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia (2008) Blood, 112, pp. 975-980; Wierda, W., O'Brien, S., Wen, S., Faderl, S., Garcia-Manero, G., Thomas, D., Do, K.A., Keating, M., Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia (2005) Journal of Clinical Oncology, 23, pp. 4070-4078; Wierda, W., O'Brien, S., Faderl, S., Ferrajoli, A., Wang, X., Do, K.A., Garcia-Manero, G., Keating, M., A retrospective comparison of three sequential groups of patients with Recurrent/Refractory chronic lymphocytic leukemia treated with fludarabine-based regimens (2006) Cancer, 106, pp. 337-345; Zhou, Y., Tang, G., Medeiros, L.J., McDonnell, T.J., Keating, M.J., Wierda, W.G., Wang, S.A., Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (2012) Modern Pathology, 25, pp. 237-245
Keywords
- CD23
- Chronic lymphocytic leukaemia
- Lumiliximab
- Small lymphocytic lymphoma
- cyclophosphamide
- fludarabine
- lumiliximab
- rituximab
- antineoplastic agent
- monoclonal antibody
- vidarabine
- adult
- aged
- Article
- autoimmune hemolytic anemia
- autoimmune thrombocytopenia
- bronchitis
- cancer survival
- cause of death
- chronic lymphatic leukemia
- controlled study
- drug dose escalation
- drug efficacy
- drug safety
- drug tolerability
- drug withdrawal
- febrile neutropenia
- female
- human
- incidence
- leukemia relapse
- leukopenia
- major clinical study
- male
- multicenter study
- multiple cycle treatment
- nausea
- overall survival
- pancytopenia
- phase 2 clinical trial
- phase 3 clinical trial
- pneumonia
- priority journal
- progression free survival
- randomized controlled trial
- rhinopharyngitis
- sinusitis
- treatment response
- tumor lysis syndrome
- upper respiratory tract infection
- urinary tract infection
- very elderly
- analogs and derivatives
- clinical trial
- comparative study
- Leukemia, Lymphocytic, Chronic, B-Cell
- middle aged
- recurrent disease
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Murine-Derived
- Antineoplastic Combined Chemotherapy Protocols
- Cyclophosphamide
- Female
- Humans
- Male
- Middle Aged
- Recurrence
- Vidarabine
