Pembrolizumab, pomalidomide and low dose dexamethasone for relapsed/refractory multiple myeloma
Mené sur 48 patients atteints d'un myélome multiple réfractaire ou récidivant (âge médian : 64 ans), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant pembrolizumab, pomalidomide et faibles doses de dexaméthasone (durée médiane de suivi : 15,6 mois)
Résumé en anglais
This is the first trial to investigate PD-1 inhibitor, pembrolizumab, and an IMiD (pomalidomide) in MM with promising clinical efficacy.PD-L1 expression on myeloma cells and PD-1 on marrow infiltrating T lymphocytes are potential biomarkers for efficacy of PD-1 blockade. Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance anti-myeloma cellular immunity generated by pomalidomide leading to improved clinical responses. In this single-center, phase II study, 48 patients with relapsed/refractory MM (RRMM) received 28-days cycles of pembrolizumab, 200 mg intravenously every 2 weeks, pomalidomide 4 mg daily for 21 days and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years and had received both immune modulatory agent and proteasome inhibitor; (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant and (30 [62%]) had high-risk cytogenetics. Adverse events grade 3-4 occurred in (19 [40%] of 48 patients) including hematologic toxicities (19 [40%]), hyperglycemia (12 [25%] and pneumonia (7 [15%]). Autoimmune events included pneumonitis (6 [13%]) and hypothyroidism (5[10%]), mostly ≤ grade 2. Objective responses occurred in (29 [60%] of 48) patients including: sCR/CR (4 [8%]), VGPR (9 [19%]) and PR (16 [33%]); median duration of response was 14.7 months (95% CI 7.9-17.5). At median follow-up of 15.6 months (95% CI 9.2-17.5), progression free survival (PFS) was 17.4 months (95% CI 11.7-18.8) and overall survival was not reached (95% CI 18.9-NR). Analyses of pretreatment marrow samples revealed a trend for increased expression of PD-L1 in responding patients and longer PFS with increased T-lymphocyte infiltrates, irrespective of PD-1 expression. Pembrolizumab, pomalidomide and low-dose dexamethasone has acceptable safety and durable responses in RRMM patients.
