Title :

Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients

Author(s) :

Alcantara, Marion [Auteur]
Chevrier, Marion [Auteur]
Jardin, Fabrice [Auteur]
Schmitt, Anna [Auteur]
Houillier, Caroline [Auteur]
Oberic, Lucie [Auteur]
Chinot, Olivier [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Peyrade, Frédéric [Auteur]
Houot, Roch [Auteur]
Hoang-Xuan, Khê [Auteur]
Ghesquieres, Hervé [Auteur]
Soussain, Carole [Auteur]

Journal title :

Journal of Hematology and Oncology

Abbreviated title :

J Hematol Oncol

Volume number :

17

Pages :

86

Publisher :

BioMed Central

Publication date :

2024-09-19

ISSN :

1756-8722

English keyword(s) :

Primary central nervous system lymphoma
Phase IB trial
Ibrutinib
Lenalidomide

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Cancer

English abstract : [en]

Background Results of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown ...
Show more >Background Results of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy. Methods Patients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle. Results Twenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell’s syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively. Conclusion Targeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Submission date :

2024-12-08T22:08:09Z
2024-12-20T15:41:34Z