Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network

Autor: Roch Houot, Khê Hoang-Xuan, Aline Clavert, Hervé Ghesquières, A. El Yamani, Eileen M Boyle, Marie Blonski, Sylvain Choquet, M. Ertault de la Bretonnière, Cécile Moluçon-Chabrot, Nathalie Cassoux, Valérie Touitou, Fontanet Bijou, Carole Soussain, S. Leruez, Maryline Barrie, E. Nicolas-Virelizier, S. Coisy, M.L. Lelez, M. Daniau, Caroline Houillier, Remy Gressin, D. Leclercq, Keyvan Rezai
Přispěvatelé: Institut Curie [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Bergonié [Bordeaux], UNICANCER, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), European Molecular Biology Laboratory [Grenoble] (EMBL), Hôpital Lapeyronie [Montpellier] (CHU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Janssen BiotechPharmacyclicsJanssen Biotech, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Rok vydání: 2019
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
Lymphoma
Phases of clinical research
Gene mutation
Central Nervous System Neoplasms
chemistry.chemical_compound
0302 clinical medicine
Piperidines
hemic and lymphatic diseases
Prospective Studies
Relapse
ComputingMilieux_MISCELLANEOUS
Aged
80 and over
Ibrutinib
Middle Aged
Prognosis
3. Good health
Survival Rate
030220 oncology & carcinogenesis
Toxicity
Female
medicine.medical_specialty
Retinal Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
Primary vitreoretinal lymphoma
03 medical and health sciences
Refractory
Internal medicine
medicine
Humans
Aged
Salvage Therapy
business.industry
Adenine
Induction chemotherapy
medicine.disease
Clinical trial
030104 developmental biology
Pyrimidines
chemistry
Primary CNS lymphoma
Drug Resistance
Neoplasm
Pyrazoles
Neoplasm Recurrence
Local
business
Follow-Up Studies
Zdroj: European Journal of Cancer
European Journal of Cancer, 2019, 117, pp.121-130. ⟨10.1016/j.ejca.2019.05.024⟩
European Journal of Cancer, Elsevier, 2019, 117, pp.121-130. ⟨10.1016/j.ejca.2019.05.024⟩
ISSN: 1879-0852
0959-8049
DOI: 10.1016/j.ejca.2019.05.024⟩
Popis: Background Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL Patients and methods This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 30%). Results Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7–30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8–12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. Conclusion Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. Clinical trial number NCT02542514 .
Databáze: OpenAIRE
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