Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group
Por:
Ocio EM, Motlló C, Rodríguez-Otero P, Martínez-López J, Cejalvo MJ, Martín-Sánchez J, Bladé J, García-Malo MD, Dourdil MV, García-Mateo A, de Arriba F, García-Sanz R, de la Rubia J, Oriol A, Lahuerta JJ, San-Miguel JF and Mateos MV
Publicada:
1 feb 2021
Ahead of Print:
1 jun 2020
Categoría:
Hematology
Resumen:
This phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) patients. Forty-seven RRMM patients with a median of three prior lines (2-8) and 94% refractory to lenalidomide were included: 14 in phase I and 33 in phase II. The recommended dose was 1 center dot 25 mg/m(2) of filanesib on days 1, 2, 15, 16, with pomalidomide 4 mg on days 1-21 and dexamethasone 40 mg weekly. The defined threshold for success was achieved, with 18 out of 31 patients obtaining at least minor response (MR) in the phase II. In the global population, 51% of patients achieved at least partial response (PR) and 60% >= MR, resulting in a median progression-free survival (mPFS) of seven months and overall survival (OS) of 19 months. The main toxicity was haematological. Importantly, patients with low serum levels of alpha 1-acid glycoprotein (AAG) at baseline (<800 mg/l) had a superior response (overall response rate of 62% vs. 17%; P = 0 center dot 04), which also translated into a longer mPFS (9 vs. 2 months; P = 0 center dot 014). In summary, filanesib with pomalidomide and dexamethasone is active in RRMM although with significant haematological toxicity. Most importantly, high levels of AAG can identify patients unlikely to respond to this strategy.
Filiaciones:
Ocio EM:
Hospital Universitario Marqués de Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain
Motlló C:
ICO Badalona, Hospital Germans Trias i Pujol, Badalona, Spain
Rodríguez-Otero P:
Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona, Spain
Martínez-López J:
Hospital 12 de Octubre, Universidad Complutense, CNIO, Madrid, Spain
:
Hospital Universitario Doctor Peset. Departamento de Medicina Interna y Odontología, Universidad Católica de Valencia, Valencia, Spain
Martín-Sánchez J:
Hospital Universitario Virgen del Rocío, Sevilla, Spain
Bladé J:
Hospital Clinic de Barcelona, Barcelona, Spain
García-Malo MD:
Hospital Morales Meseguer, IMIB-Arrixaca, Murcia, Spain
Dourdil MV:
Hospital Clínico Lozano Blesa, IIS Aragón, Zaragoza, Spain
García-Mateo A:
Hospital General de Segovia, Segovia, Spain
de Arriba F:
Hospital Morales Meseguer, IMIB-Arrixaca, Murcia, Spain
García-Sanz R:
Complejo Asistencial Universitario de Salamanca (IBSAL) y Centro de Investigación del Cáncer (IBMCC-CSIC), Universidad de Salamanca, Salamanca, Spain
:
Hospital Universitario Doctor Peset. Departamento de Medicina Interna y Odontología, Universidad Católica de Valencia, Valencia, Spain
Oriol A:
ICO Badalona, Hospital Germans Trias i Pujol, Badalona, Spain
Lahuerta JJ:
Hospital 12 de Octubre, Universidad Complutense, CNIO, Madrid, Spain
San-Miguel JF:
Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona, Spain
Mateos MV:
Complejo Asistencial Universitario de Salamanca (IBSAL) y Centro de Investigación del Cáncer (IBMCC-CSIC), Universidad de Salamanca, Salamanca, Spain
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