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958 Improvement in Global Longitudinal Strain (GLS) Correlates with NT-Probnp Response in Patients with Cardiac Amyloidosis Treated on a Phase 1b Study of Anti-Amyloid Mab Cael-101

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma: Therapy, excluding Transplantation: Immunotherapies in Plasma Cell Disorders
Hematology Disease Topics & Pathways:
antibodies, Biological, Diseases, Adult, Therapies, Biological Processes, Technology and Procedures, Study Population, Plasma Cell Disorders, Clinically relevant, Lymphoid Malignancies, immune mechanism
Monday, December 3, 2018: 5:15 PM
Ballroom 20A (San Diego Convention Center)

Divaya Bhutani, MD 1, Siyang Leng, MD2, Andrew Eisenberger, MD3, Mathew S. Maurer, MD4*, Sofia Shames, MD5*, Jeff Goldsmith, PhD6* and Suzanne Lentzsch, MD, PhD7

1Herbert Irving comprehensive cancer center, Columbia University medical Center, New York
2Division of Hematology and Oncology, Columbia University Medical Center, New York, NY
3Division of Hematology, Columbia University Irving Medical Center, New York, NY
4Division of Cardiology, Columbia University, New York, NY
5Cardiology, Columbia University medical Center, New York
6Department of Biostatistics, Columbia University, New York
7Division of Hematology/Oncology, Columbia University, New York, NY

Background: Cardiac AL amyloidosis continues to have poor prognosis with median survival of less than a year from diagnosis and only 3 months in patients with cardiac stage 3b disease (1). Targeting the underlying plasma cell clone can clear circulating light chains but cannot remove deposited protein in the organs. CAEL-101 (11-1F4 mAb) is a monoclonal IgG1 antibody that directly binds to a conformational epitope present on both human kappa and lambda light-chain amyloid fibrils. In preclinical studies the antibody was able to localize to the amyloid tissue and led to decrease in size as well as elimination of the amyloid protein (2). An open-label phase 1b clinical trial of the CAEL-101 showed a promising organ response rate of 63% (3). Global Longitudinal Strain (GLS) is a sensitive measure of functional impairment in cardiac AL Amyloidosis, and may predict survival over and above that of cardiac biomarkers (4). Here, we evaluated the effects of CAEL-101 on the myocardial function using GLS in correlation with NT-proBNP in patients with cardiac amyloidosis treated with CAEL-101.

Methods: Patients with relapsed/refractory AL amyloidosis were enrolled and treated in a phase 1b study (N=19) using the anti-amyloid mAb CAEL-101. CAEL-101 was administered weekly for 4 weeks with sequential doses of 0.5, 5, 10, 50, 100, 250 and 500 mg/m2 in a dose-escalation design. All patients underwent transthoracic echocardiograms at screening and 12 weeks. GLS was measured using speckle-tracking (TomTec-Arena 1.2, Germany) and calculated as an average of 4-, 2-, and 3- chamber based measurements. Paired student’s t-test was used to compare echocardiographic variables at screening and 12 weeks after therapy start with CAEL-101. GLS was correlated with NT-proBNP using Pearson correlation coefficient.

Results: The median age of patients (N=19) was 63 years with 68% male and 32% female. Ten out of 19 patients had cardiac involvement with a median NT-proBNP of 1186 (range 699-3964) at screening. Six out of 10 patients (60%) with cardiac involvement met cardiac response criteria by having a decrease in NT-proBNP >30% (3). Among echocardiographic parameters, mean GLS improved significantly in 9/10 patients from -15.58 ± -4.14% at screening to -17.37 ± -3.53% at week 12, p = 0.004 (Figure 1) of the trial. One patient who did not have improvement in GLS was dosed at low dose level 2 (5mg/m2) in the study. Under the null hypothesis, the probability of 9 or more patients improving without drug effect, is ~0.0107, suggesting that improvement of GLS in 9 of 10 is a highly unlikely outcome unless the there is a drug association. In contrast to the improved GLS in cardiac patients, CAEL-101 had no significant effect (p=0.4829) on GLS in the 9 patients without cardiac involvement (GLS -22.77 ± -3.12 at screening and -22.36 ± -3.02 at end of treatment), suggesting a specific effect of CAEL-101 on cardiac amyloid deposits (Figure 2 and Table 1). Pearson correlation coefficient between NT-proBNP response and GLS response (in 8 cardiac evaluable patients) was 0.345, further confirming the efficiency of Cael-101 in amyloid resolution resulting in structural remodeling of the heart muscle.


Improvement in GLS correlates with improvement in NT-proBNP in in patients with cardiac AL Amyloidosis treated with CAEL-101. The short timeframe in which the improvement of the GLS occurred (12 weeks after entering the trial) suggests that this effect is Ab related and GLS along with NT-proBNP should be evaluated in larger studies as markers for early cardiac response in patients with AL Amyloidosis.


  1. Wechalekar AD, Schonland SO, Kastritis E et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood.2013;121(17):3420-7.
  1. Wall JS, Kennel SJ, Stuckey AC et al. Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Blood. 2010 Sep 30;116(13):2241-4.
  1. Edwards CV, Gould J, Langer AL et al. Final Analysis of the Phase 1a/b Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients with Relapsed or Refractory AL Amyloidosis. Blood 2017 130:509.
  1. Salinaro F, Meier-Ewert HK, Miller EJ et al. Longitudinal systolic strain, cardiac function improvement and survival following treatment of light-chain (AL) cardiac amyloidosis. Eur Heart J Cardiovasc Imaging.2017 Sep 1;18(9):1057-1064.

*Dr. Lentzsch recused herself from the Phase 1a/b trial in 11/2017.

    Disclosures: Maurer: Glaxo Smith kline: Other: personal fees ; Eidos: Other: Personal fees, Research Funding; Pfizer: Other: Personal fees, Research Funding; Prothena: Research Funding; Alnylam: Research Funding; Ionis: Other: Personal fees, Research Funding; Akcea: Other: Personal fees. Lentzsch: BMS: Consultancy; Caelum Biosciences: Consultancy, Other: Dr. Lentzsch recused herself as an investigator from the Phase 1a/b trial testing CAEL-101 in 11/2017., Patents & Royalties: Shareholder for Caelum Biosiences; Bayer: Consultancy; Janssen: Consultancy.

    *signifies non-member of ASH