First report of outcomes in patients with stage IIIb AL amyloidosis treated with Dara–VCD front‐line therapy

Summary 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.