Lo studio di fase 2 GRIFFIN ha mostrato risultati importanti con il quadripletto sperimentale a base di Daratumumab ( Darzalex ) nel trattamento del mieloma multiplo di nuova diagnosi nei pazienti idonei al trapianto
A conclusione dell’analisi finale, dopo un follow-up mediano di 49.6 mesi, una riduzione del 55% del rischio di progressione della malattia o morte è stata osservata nei pazienti nel braccio Daratumumab-RVd; un tasso stimato di sopravvivenza libera da progressione ( PFS ) a 48 mesi dell’87.2% è stato osservato nel braccio Daratumumab-RVd, contro il 70% nel braccio RVd.
La sopravvivenza PFS mediana non è stata raggiunta in entrambi i bracci di trattamento. Inoltre, dopo un lungo follow-up, non sono emersi nuovi problemi di sicurezza.
ENGLISH VERSION
The final analysis of the GRIFFIN trial has shown the potential benefit of adding Daratumumab ( Darzalex ) to RVd for the treatment of newly diagnosed, transplant-eligible patients.
The evaluation of this treatment regimen will continue as part of the registrational, phase 3 PERSEUS study.
About the GRIFFIN Study
The phase 2 GRIFFIN study has evaluated the investigational regimen of Daratumumab in combination with RVd and enrolled and treated more than 200 adults ages 18-70 years with newly diagnosed multiple myeloma who were eligible for ASCT.
In the safety run-in cohort, 16 patients received 25 mg of Lenalidomide orally on days 1-14;
1.3 mg/m2 of Bortezomib subcutaneously on days 1, 4, 8 and 11; and 20 mg of Dexamethasone on days 1, 2, 8, 9, 15 and 16, and every 21 days during the induction and consolidation phases ( cycles 1-6 ). Daratumumab 16 mg/kg IV was given on days 1, 8 and 15 of cycles 1-4 and on day 1 of cycles 5-6.
During the maintenance phase ( cycles 7-32 ), patients received 10 mg daily of Lenalidomide
( 15 mg beginning at cycle 10 if tolerated ) on days 1-21 every 28 days and Daratumumab 16
mg/kg IV every 56 days; this was amended to every 28 days based upon emerging clinical
pharmacokinetic data demonstrating improved target saturation with every-4-week
maintenance dosing. Maintenance therapy with Lenalidomide could be continued beyond cycle
32, per local standard of care.
In the subsequent randomized phase 2 portion of the study, 207 patients were randomized
to treatment with RVd induction and consolidation, ASCT, and maintenance therapy with
Lenalidomide; or Daratumumab-RVd, ASCT, and maintenance therapy with Daratumumab and
Lenalidomide.
Darzalex has been approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.
Darzalex has become a backbone therapy in the treatment of multiple myeloma, having been used in the treatment of more than 300,000 patients worldwide and more than 68,000 patients in the U.S. alone since its U.S. FDA approval in 2015.
Daratumumab is the first CD38-directed antibody approved globally to treat multiple myeloma.
CD38 is a surface protein that is present in high numbers on multiple myeloma cells,
regardless of the stage of disease.
Daratumumab binds to CD38 and inhibits tumor cell growth, causing myeloma cell death. Daratumumab may also have an effect on normal cells.
Data across eight phase 3 clinical trials, in both the frontline and relapsed settings, have shown
that Daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.
