Key Points
- Daratumumab monotherapy in stage IIIB AL amyloidosis showed rapid hematologic responses (75%; median time 1 week) and 65% 6-month survival.
- Treatment was feasible, well tolerated, and achieved 30% cardiac response at 6 months in this high-risk population.
Treatment options for patients with immunoglobulin light chain (AL) amyloidosis and advanced cardiac involvement remain limited. The prospective, phase 2 EMN22 trial included previously untreated patients with AL amyloidosis, measurable hematologic disease, and Mayo2004/European cardiac stage IIIB to receive daratumumab monotherapy at the standard dose and schedule for up to two years (28-day cycles); patients with inadequate response after three cycles could additionally receive bortezomib weekly and dexamethasone. The primary endpoint was 6-month overall survival (OS) rate. Of 40 enrolled patients, ten (25.0%) received additional treatment with bortezomib and dexamethasone. The 6-month OS rate was 65.0% (95% CI, 48.2-77.6) and median OS was 10.4 months. The best hematologic response rate (partial response or better) up to six months was 75.0% (very good partial response or better: 47.5%; complete response: 12.5%), the median time to the first and best hematologic response being one week and 2.3 months, respectively. The cardiac response rate at six months was 30.0%. Common serious adverse events were cardiac failure (25.0%), sudden cardiac death (10.0%), and acute kidney injury (7.5%). The patients' quality of life remained stable throughout the trial treatment and observation. In patients with high-risk, advanced (stage IIIB) AL amyloidosis, daratumumab monotherapy was feasible and well-tolerated, achieving rapid hematologic responses and associated with prolonged survival relative to historical cohorts. Cardiac response rates at 6 months were significant, considering the advanced cardiac disease. These findings support daratumumab as the backbone of anti-clonal therapy in advanced cardiac AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT04131309.