First Report of Outcomes in Patients with Stage IIIb AL Amyloidosis Treated with Dara-VCD Front-line Therapy

Although Dara-VCD (daratumumab-bortezomib-cyclophosphamide-dexamethasone) has revolutionized the treatment of newly diagnosed Amyloid Light chain (AL) amyloidosis, patients with stage IIIb disease were excluded in the pivotal trial. We performed a multicentre retrospective cohort study to investigate the outcomes of 19 consecutive patients treated with Dara-VCD front-line therapy who had stage IIIb AL at diagnosis. More than two thirds presented with New York Heart Association Class III/IV symptoms, and had a median of two organs involved (range, 2-4). The haematologic overall response rate was 100%, with 17/19 patients (89.5%) achieving a very good partial response (VGPR) or better. Haematologic responses were achieved rapidly, as evidenced by 63% of evaluable patients with involved serum free light chains (iFLC) < 2 mg/dl and the difference between involved and uninvolved serum free light chains (dFLC) <1 mg/dl at three months. Among 18 evaluable patients, 10 (56%) achieved a cardiac organ response and six (33%) cardiac VGPR or better. The median time to first cardiac response was 1.9 months (range, 0.4-7.3). At a median follow-up of 12 months for surviving patients, estimated one-year overall survival was 67.5% [95% confidence interval (CI), 43.8-84.7]. The incidence of grade 3 or higher infections was 21%, with no infection-related mortality thus far. In summary, Dara-VCD has a promising efficacy and safety profile in stage IIIb AL, and should be studied in prospective trials.