Publication

Abstract : BACKGROUND : Light chain amyloidosis(AL) is a rare form of plasma cell dyscrasia wherein insoluble amyloid fibrils are deposited in vital organs like heart and kidney resulting in irreversible damage and poor overall survival. Early diagnosis requires multidisciplinary team skills. Cardiac imaging and markers helps to predict prognosis and follow up imaging would help in response assessment. Herein, we report a retrospective analysis of cardiac amyloidosis from South Asia with focus on comparative (objective) analysis between therapy arms with respect to cardiac assessment and progression free survival, a real world data. METHODOLOGY:A retrospective study of patients (n=98) newly diagnosed as systemic amyloidosis AL with cardiac involvement registered at two tertiary cancer care centres in Kochi, India during the time period 1st January 2005 to 1st March 2022 was conducted. Patients included had biopsy proven amyloid in atleast one cardiac (n=2/98, 02%)/extracardiac (n=96/98, 98%) biopsy , suspected amyloidosis in Global Longitudinal Echocardiographic (n=56/71, 79%)/Cardiac Magnetic Resonance Imaging(n=56/71,79%) , serum light chain restriction in n=57/98, 58% (lambda restricted n= 32/57, 56% and kappa restricted n= 25/57, 44%), bone marrow biopsy IHC proven (n=29/98, 29%),and/or Congo red positive with apple green birefringence in n=16/98 (17%) cases . Patients were further subgrouped on the basis of Mayo 2004 classification and type of induction therapy received [cyclophosphamide-bortezomib-dexa (CyBorD) versus melphalan, thalidomide, lenalidomide, bortezomib (non CyBorD)]. Post induction maintenance (single agent) or treatment free period was included as an independent variable for comparison. Statistical analysis was done using SPSS 2022 version 1.0.0 and contingency tables. RESULTS: Baseline characteristics are shown in Table 1. Patients who received induction chemotherapy with exclusive CyBorD, n=44/98 (45%) were compared with patients who received dexamethasone with other immunomodulatory agents n=54/98 (55%) . Those receiving CyBorD had a statistically significant progression free period (9.2 vs 2.4 months, p<0.0001, student T test) as compared to others.The documented mortality in the Mayo Stage I,II cohort treated with CyBorD in induction was markedly lower than in Mayo I,II treated with other therapy lines as well as in Mayo IIIa, IIIb irrespective of the induction regimen [ p<0.05 , Fischer exact test]. With respect to change in ejection fraction (latest vs baseline) on Global Longitudinal ECHO , patients treated with CyBorD (n=38/44 in baseline and n=11/44 in follow up) showed a lesser worsening of the EF which was not statistically significant as compared to non-CyBorD cohort (n=33/54 in baseline and n=15/54 in follow up) which showed a significant worsening of EF post therapy [p<0.001, Fisher exact test]. Similarly , while comparing diastolic dysfunction (DD), there was no significant worsening of grade of DD in CyBorD arm (n= 32/44 baseline, n=18/44 follow up, p=0.06, Fischer exact test). However, there was a statistically significant increase in grade of DD in non-CyBorD arm (n=29/54 baseline, n=9/54 follow up, p=0.01, Fischer exact test) CONCLUSION: The study, which is probably the first of its kind from tertiary cancer care centres in South Asian region , throws light on the need for comparative cardiac monitoring using global longitudinal ECHO , cardiac MRI and statistically significant benefits in subsequent assessments and progression free survival with CyBorD. Consequential to other significant findings, it may be true to state that early cardiac imaging and initiation of CyBorD can contribute to superior outcomes in cardiac amyloidosis diagnosed in early stages.