The prognostic value of global longitudinal strain in patients with AL amyloidosis with cardiac involvement treated with up-front daratumumab, cyclophosphamide, bortezomib and dexamethasone

Introduction Immunoglobulin light-chain (AL) amyloidosis is a plasma cell dyscrasia characterised by misfolding and extracellular deposition of monoclonal light chains - cardiac involvement is the principal determinant of mortality [1]. Daratumumab, an anti-CD38 monoclonal antibody, combined with the traditional treatment of cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) achieves partial haematologic responses or better in 78.5% of patients with newly diagnosed AL amyloidosis compared to 49.2% treated with CyBorD alone [2]. Global longitudinal strain (GLS) stratified by ≥ -9.0%, ≥ -12.1% and ≥ -16.1% has been found to independently predict both response to therapy and overall survival times [3]. The systemic AL (sAL) score, developed to rule-in and rule-out AL-CM, was stratified by 0-2 as low, 3-4 as moderate and 5-6 as high severity, categories shown to correlate with amyloid burden on cardiac MRI [4]. Purpose We examined our own cohort of patients with confirmed light chain cardiac amyloidosis (AL-CM) who received upfront Dara-CyBorD to assess the prognostic value of GLS and a GLS-containing score. Methods Retrospective chart review was conducted under an IRB-approved protocol among initial referral visits seen at our amyloidosis referral centre. 49 patients with MRI or biopsy-proven AL-CM had received upfront Dara-CyBorD, 30 of whom had echocardiography with the parameters (E/E’, RWT, GLS, TAPSE) needed to calculate the sAL score. 26 had cardiac MRI or endomyocardial biopsy-confirmed AL-CM; 4 had clinical symptoms of heart failure with positive non-cardiac biopsy. Overall survival was stratified by GLS and sAL category. Patients with follow-up echocardiography (n=5) had their GLS and sAL categories recalculated to assess for any changes. Results The primary outcome was overall survival (OS). 23/30 (76.7%) of patients were alive as of last follow-up. Median follow-up was 29.9 months. Median survival was not reached. In the GLS ≥ -9.0% group (n=1), 1 patient died 6 months after diagnosis. In the -12.2% to -9.1% group (n=6), 2 patients died on average 8 months after diagnosis. In the -16.1% to -12.1% group (n=5), 1 patient died 101 months after diagnosis. In the ≤ -16.2% group (n=17), 3 patients died on average 17 months after diagnosis. When stratified by sAL score, the high severity group (n=16) had 5 deaths on average 12 months after diagnosis, the moderate severity group (n=7) had 1 death 101 months after diagnosis; the low severity group (n=8) had 1 death 16 months after diagnosis. Of note, among the 10 patients with follow-up echocardiograms with complete parameters to calculate another AL score, only 1 had any change in their sAL score-based category (from high to moderate) while 5 had changes in their GLS-based category (3 improved; 2 worsened). Conclusions The sAL score has a higher prognostic value than GLS alone in our population of patients with confirmed systemic AL amyloidosis with cardiac involvement.