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%).

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

 



Posted on 9 August 201927 March 2024