Organ responses with daratumumab therapy in previously treated AL amyloidosis

• Published in: Blood advances 2020-02, Vol.4 (3), p.458-466
• Main Authors: Chung, Alfred, Kaufman, Gregory P., Sidana, Surbhi, Eckhert, Erik, Schrier, Stanley L., Lafayette, Richard A., Arai, Sally, Witteles, Ronald M., Liedtke, Michaela
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - therapeutic use; Humans; Immunoglobulin Light-chain Amyloidosis - drug therapy; Lymphoid Neoplasia; Retrospective Studies; Treatment Outcome
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2019000776

Immunoglobulin light chain amyloidosis (AL amyloidosis) involves deposition of abnormally folded light chains into a wide range of tissues causing organ dysfunction, including in the heart and kidney. Daratumumab, a CD38-targeted antibody, has recently demonstrated efficacy in producing hematologic responses in previously treated disease. However, data on survival outcomes and organ responses to daratumumab are lacking. Seventy-two patients with previously treated AL amyloidosis who received daratumumab monotherapy with dexamethasone were retrospectively evaluated. With a median follow-up of 27 months, 2-year overall survival (OS) was 86.9% (median OS, not reached) and 2-year time-to-next treatment or death (TTNT)–free survival was 62% (median TTNT, not reached). Forty of 52 evaluable patients achieved a hematologic response (77%), with >60% of patients achieving a very good partial response or better; median time-to-hematologic response was 1 month. Fifty-seven patients (79%) had cardiac involvement, and 55% of evaluable patients achieved a cardiac response, with a median response time of 3.2 months among responders. Cardiac responses were associated with an improvement in OS, with landmark analysis for cardiac responses at 3 months trending toward statistical significance (100% vs 55% at 30 months, P = .051). Forty-seven patients (65%) had renal involvement, and 52% of evaluable patients achieved a renal response, with a median response time of 6 months among responders; there was no significant difference in OS between renal responders and nonresponders. This study demonstrates that daratumumab is highly effective in the treatment of previously treated AL amyloidosis, and a significant proportion of patients can achieve deep hematologic responses, as well as improvements in organ function. •Daratumumab is effective in reversing organ damage in patients with previously treated AL amyloidosis. [Display omitted]