Front-line daratumumab in newly diagnosed AL amyloidosis patients.

Abstract

e20569 Background: Light chain amyloidosis (AL) is a plasma cell dyscrasia characterized by organ dysfunction, morbidity, and early mortality. Treatment focuses on suppressing monoclonal light chain production as measured by hematologic response criteria (Comenzo et al., 2012). Daratumumab (DARA), a monoclonal CD38 antibody, has demonstrated efficacy in heavily pretreated AL patients (Kaufman et al., 2017). We report the outcomes of newly diagnosed AL patients treated with a DARA-based regimen. Methods: A single-center retrospective chart review with an IRB-approved protocol was performed on newly diagnosed AL patients treated with first line DARA-based regimens between 1/2018 – 12/2019. Results: Fourteen patients were evaluated. The median age was 69 years (45 – 87), 50% were male, and 50% produced monoclonal lambda light chains. All patients had cardiac and renal involvement. Per the 2004 Mayo staging system, 1/14 (7%) patients had stage I cardiac disease, 2/14 (14%) had stage II, and 11/14 (79%) had stage III, of which two were stage IIIb. Regarding renal staging (Palladini et al., 2014), 10/14 (71%) patients were stage I, 3/14 (21%) stage II, and 1/4 (7%) stage III. Most patients (11/14) received DARA in combination with bortezomib and dexamethasone, while one patient received DARA and dexamethasone (DEX). Two patients received DARA in combination with bortezomib, cyclophosphamide, and DEX. Patients received a median of 5 cycles of DARA (1 – 14). After a median follow-up of 4.4 months (1 – 19), all patients were still receiving DARA. DARA was well tolerated, with 4 patients (29%) experiencing grade 1 infusion reactions and no additional toxicities observed. Responses were rapid, with a median time of 11 days (7 – 61) to first response and 46 days (9 8– 168) to best response. First response was classified as partial response (PR) in 8/14 patients (57%), very good PR (VGPR) in 3/14 (21%), and complete response (CR) in 1/14 (7%). Best response included a PR in 3/14 (21%), VGPR in 7/14 (50%), and CR in 2/14 (14%). In most patients, responses deepened over time. Cardiac response was seen in 5/7 (71%) evaluable patients with median time to response of 39 days (21 – 263). Renal response was seen in 2/4 (50%) evaluable patients with median time to response of 152 days (94 – 194). Conclusions: First line use of DARA in AL amyloidosis produced rapid and deep hematologic and organ response, resulting in a 93% objective hematologic response rate. DARA was well-tolerated and efficacious even among patients with extensive organ involvement and cardiac dysfunction. Prospective studies of first line DARA are warranted.