Highlights from

EHA 2019

European Hematology Association

Amsterdam 13-16 June 2019

Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone in patients with newly diagnosed amyloid light chain amyloidosis

Prof. Raymond Comenzo (Tufts University, USA) presented 1-year follow-up data from the phase 3 ANDROMEDA trial; the combination of subcutaneous daratumumab with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) led to high overall and complete response (CR) rates in patients with newly diagnosed amyloid light chain (AL) amyloidosis.

In the safety run-in single arm phase of ANDROMEDA, 28 patients (median age 68 years; range 35-83 years) with previously untreated AL amyloidosis received daratumumab 1,800 mg (formulated with recombinant human hyaluronidase PH20) administered subcutaneously once a week during cycles 1 and 2, every 2 weeks during cycles 3 through 6, and every 4 weeks thereafter for up to 2 years. Patients also received CyBorD, with cyclophosphamide 300 mg/m2, bortezomib 1.3 mg/m2, and dexamethasone 40 mg, administered once weekly for up to 6 treatment cycles. Researchers followed patients for a median of 341 days (range 17-449 days), with median treatment duration of 11 months (range 0.2-14 months).

The primary endpoint was overall complete haematologic response rate, evaluated every 4 weeks during cycles 1 through 6 and every month thereafter. All but one patient (n=27; 96%) responded to treatment with daratumumab plus CyBorD. Most responders achieved at least a very good partial response (VGPR; 82%), with 10 achieving a CR. The median times to CR and VGPR were 85 days (range 29-226 days) and 22 days (range 7-228 days), respectively.

The one patient whose disease did not respond to treatment eventually experienced disease progression while on the study. However, “all 10 patients who achieved a CR continue to respond to treatment,” Dr Comenzo reported. The median duration of CR had not been reached. Six participants went on to receive subsequent autologous haematopoietic cell transplantation; 4 of these patients have died (2 due to disease progression and 2 due to events following transplant). The most common treatment-related adverse events included diarrhoea (64%), fatigue (50%), and peripheral oedema (50%).

  1. Comenzo RL et al. Abstract S875, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.

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