Background: AL (light-chain) amyloidosis, the common form of the complex spectrum of amyloidosis, poses significant diagnostic and therapeutic challenges even in well-resourced healthcare settings owing to non-specific symptoms, delayed diagnosis, limited therapeutic options and the need for specialised diagnostic techniques. In resource-limited settings such as India, these challenges are further compounded by constraints in healthcare infrastructure, limited access to advanced diagnostic tools and high costs of treatment. In 2023, our hospital established an Amyloid Centre (Amrita Amyloid Center) aimed at improving the diagnosis, treatment, and overall management of amyloidosis. This retrospective study analyses clinical data from the past two decades to identify the key challenges faced in the diagnosis and treatment of AL amyloidosis in a resource-limited setting.

Methodology: Retrospective data was retrieved from in-house electronic records using keywords (amyloid, amyloidosis light chain, systemic, primary) from February 2002 to July 2024. All patients diagnosed during this period were included. Diagnosis was based on clinical, biochemical, cardiac imaging and histopathological criteria consistent with AL amyloidosis. Patient data included demographics, presenting symptoms, organ involved, diagnostic modalities and treatment regimens [chemotherapy, stem cell transplantation (SCT), supportive care] .Outcomes measured included time to diagnosis (TTD) (from symptom onset to confirmed diagnosis), diagnostic challenges , therapy outcomes and treatment-related challenges .Temporal trends and associations with time of diagnosis were examined for all variables using conditional density plots, linear regression model with a restricted cubic spline, Spearman rank correlation test and F-test. All statistical analyses were conducted using R version 4.3.0.

Results : A total of 448 patient records were screened. The following were excluded- confirmatory report unavailable n=139(31.0%), biopsy proven congophilic amyloidosis but no further data available n=56 (12.5%), cutaneous amyloidosis (lichen, macular, amyloid angiopathy) n=84 (18.8%) and amyloidosis with other histologies (AA, ATTR, others)n=52(11.6%). Out of 117 patients with AL amyloid, 79 (67.5%) were males. Median age of the cohort was 67(40-94) years. Common presenting symptoms were dyspnoea on exertion (35, 29.9%), pedal edema (26, 22.2%), gastrointestinal(GI) symptoms (17,14.5%) and weakness of extremities (8, 06.4%). Serum free light chain assays confirmed light chain restriction . Biopsied tissues which demonstrated amyloid with apple green birefringence in Congo Red stain included renal n=26(22.2%), duodenal/rectal n=32(27.4%), fat pad n=19(16.2%), bone marrow n=15(12.3%) and other tissues n=10(8.5%). Median TTD was 5.5 (0-147) months. Most common organ-system involved was cardiac 40 (34.2%), followed by renal 34 ( 29.0%), Gastrointestinal 17(14.5%), liver 4(3.4%), skin 6 (5.1%), lungs and musculo-skeletal 1(0.9%) each. Median dFLC was 283 (51-6150)mg/dL. Unequivocal findings of amyloidosis were seen in echocardiogram n=30(25.6%) and cardiac magnetic resonance n=12(10.3%). Revised Mayo 2012 Staging revealed Stage I (n=37;31.6%), Stage II (n=33;28.2%), Stage III (n=15;13.5%), Stage IV (n=25;21.4%) and not classified (n=6;5.1%) patients. Amyloid typing by mass spectroscopy (MS) was done for 8 (6.4%) patients. Four (3.4%) patients died before treatment initiation. Induction therapy of the remaining 113 patients consisted of thalidomide n=16(14.2%), Mel-Pred n=15(13.27%), CyBorDex n=62(54.86%), BorLenDex n=13 (11.5%), pomalidomide n= 3 (2.6%). Autologous SCT was done in 6 (5.3%)cases. Daratumumab was used in 4 (3.5%) patients .The median follow up was 9.5 (0-150) months, with 21(17.9%) deaths registered [ most common: sudden cardiac death n=11(9.4%) followed by sepsis and AKI n=4(3.4% each)].Kaplan-Meier curves were used to predict the overall survival of patients. At the end of one year, the overall survival rate was 59.2%.

Conclusion:This study highlights the diagnostic delays and limited access to advanced diagnostic and therapeutic options for AL amyloidosis in a resource-limited setting, underscoring the need for improved healthcare infrastructure and accessible, cost-effective treatments to enhance patient outcomes.

Disclosures

No relevant conflicts of interest to declare.

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2024
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