Dual Monoclonal Antibody Therapy in Patients With Systemic AL Amyloidosis and Cardiac Involvement.

BACKGROUND

Systemic AL amyloidosis (AL) is a rare disease in which clonal immunoglobulin light chains produced by monoclonal plasma cells circulate and misfold, resulting in direct toxicity and fibrillar deposition of amyloid in numerous tissues. Early mortality from cardiac damage remains high. As depth of organ response carries a prognostic significance, combining anti-plasma cell and anti-amyloid therapies might hold the key to achieving long lasting responses. We report a series of patients who received 2 monoclonal antibodies, anti-CD38 and anti-amyloid, simultaneously.

MATERIALS AND METHODS

We describe the characteristics and outcomes of 19 patients who received daratumumab (anti-CD38) on progression with front-line therapy for AL, 9 of whom were on concurrent dual monoclonal antibody treatment with daratumumab and NEOD001 (anti-amyloid), and also provide data on the schedule, safety, and tolerability of intravenous infusions of these monoclonal antibodies.

RESULTS

The 9 patients who received treatment with dual monoclonal antibodies achieved a high rate (100%) of hematologic response in a median of 33 days. There was no significant toxicity to dual monoclonal antibody therapy. Seven of the 8 met criteria for cardiac response, achieved in less than 3 months of combined therapy. Ten patients who received daratumumab alone also had high rates of hematologic and organ responses.

CONCLUSIONS

Monoclonal antibodies with distinctly different targets can be safely combined in patients with AL and cardiac involvement. Patients experienced high rates of hematologic and cardiac response with combined anti-CD38 and anti-amyloid monoclonal antibody therapies. Further study of this combined approach is warranted.