A Phase Ib study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma
Mené sur 45 patients atteints d'un myélome multiple récidivant ou réfractaire, cet essai de phase Ib analyse les caractéristiques pharmacocinétiques puis évalue la dose maximale tolérée et la toxicité de l'isatuximab en combinaison avec du pomalidomide et de la dexaméthasone (nombre médian de thérapies précédentes : 3)
Résumé en anglais
Isatuximab combined with pomalidomide/dexamethasone has a manageable safety profile with promising clinical activity.Isatuximab 10 mg/kg (four weekly doses followed by dosing every 2 weeks thereafter) has been selected for future combination studies. This phase Ib dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly [QW] for 4 weeks, followed by every 2 weeks [Q2W]), pomalidomide 4 mg (Days 1–21), and dexamethasone 40 mg (QW) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination. Secondary objectives included evaluation of pharmacokinetics, immunogenicity, and efficacy. Forty-five patients received isatuximab (5 [n=8], 10 [n=31], or 20 [n=6] mg/kg). Patients received a median of 3 (range 1–10) prior lines; most were refractory to their last regimen (91%), with 82% lenalidomide-refractory and 84% PI-refractory. Median treatment duration was 9.6 months; 19 (42%) patients remain on treatment. Most common adverse events included fatigue (62%), and upper respiratory tract infection (42%), infusion reactions (42%), and dyspnea (40%). The most common grade ≥3 TEAE was pneumonia, which occurred in 8 patients (17.8%). Hematologic laboratory abnormalities were common (lymphopenia, leukopenia, anemia, 98% each; neutropenia, 93%; and thrombocytopenia, 84%). Overall response rate was 62%; median duration of response was 18.7 months; median progression-free survival was 17.6 months. These results demonstrate potential meaningful clinical activity and a manageable safety profile of isatuximab plus pomalidomide/dexamethasone in heavily pre-treated patients with RRMM. The 10 mg/kg QW/Q2W isatuximab dose was selected for future studies. This trial was registered at www.clinicaltrials.gov: NCT02283775.
