Daratumumab plus bortezomib and dexamethasone (Dara‐ VD ) in newly diagnosed Mayo 2004 stage IIIA and IIIB light‐chain amyloidosis: Long‐term follow‐up results from a prospective phase 2 study

Anti-CD38 monoclonal antibodies dramatically improve the prognosis in immunoglobulin light-chain (AL) amyloidosis, yet patients with end-stage (Mayo 2004 IIIB) disease are typically excluded from prospective trials. To evaluate the daratumumab plus bortezomib and dexamethasone (Dara-VD) regimen in Mayo 2004 stage III patients, we conducted a prospective phase 2 trial including 20 stage IIIA and 20 stage IIIB patients. The long-term follow-up results are reported here. The 24-month haematological complete response (CR) and very good partial response (VGPR) rate were 52.5% and 12.5% respectively. Organ responses improved after 12 months; the 24-month cardiac CR and VGPR rates were 15.0% and 35.0%. After a median follow-up of 50.9 months, 16 patients died and 10 patients had progressive diseases. The median overall survival (OS) had not been reached in either group, with a 4-year OS rate of 60.0% (95% confidence interval [CI]: 45.2%-75.2%). The median event-free survival (EFS) was 33.5 months (95% CI 21.0-46.0 months), with a 4-year EFS rate of 37.5% (95% CI: 24.3-54.7). No significant difference in OS or EFS was observed between stage IIIA and IIIB patients. In conclusion, the strong anti-plasma cell regimen Dara-VD provides comparable long-term responses and prognosis for Mayo stage IIIB patients.