ARC in the Field: Updates from ISA 2022

Special Report by:
Dr. Johana Fajardo, DNP, ANP-BC CHFN FHFSA
Infiltrative Cardiomyopathy Director, MedStar Washington Hospital Center; Chair of ARC Amyloidosis Nurse Collaborative

The XVIII International Symposium on Amyloidosis (ISA) took place September 4-8, 2022 in Heidelberg, Germany.

The congress was attended by Amyloidosis experts from around the world who meet every two years to share knowledge and best practices on the science and clinical management of Amyloidosis. The attendees include leading experts who have dedicated their lives to improving survival and quality of life for all amyloidosis patients, along with early career faculty, nursing professionals, patient organizations, and industry. ISA is an important scientific meeting where cutting-edge research and care practices are presented and discussed. This recap includes a brief snapshot of some of the many meeting highlights with the aim of bringing a broader audience into the discussion. 

“ISA is an important scientific meeting where cutting-edge research and care practices are presented and discussed.”

Predictors of Hematologic Response and Survival with Stem Cell Transplantation  

There were multiple abstracts presented in the category of Light-Chain amyloidosis (AL) that varied from basic science to new clinical strategies to improve patient outcomes. Dr. Joshua Gustine, from Boston University, presented a predictive model of hematologic response and survival with stem cell transplantation. The prognostic scoring system identifies patients that will most likely derive long-term benefit from high-dose melaphan and autologous stem cell transplantation (HDM/SCT), using hematologic and cardiac biomarkers. Although HDM/SCT was found to achieve full hematologic response in up to 39% of cases, not all AL patients may be physiologically fit to survive such an aggressive management strategy. Therefore, patient selection and risk stratification are key to ensure the success of such therapies in the AL population. Future studies to compare HDM/SCT with novel treatment strategies i.e. Daratumumab are needed to determine the role and timing of SCT. 

Looking Over Your Shoulder 

Medical student Alyssa Basdavanos surprised the ISA audience with an eloquent presentation demonstrating shoulder pathology prevalence in Amyloidosis, predating diagnosis of AL and Transthyretin Amyloidosis (ATTR) by several decades. In the discussion, Ms. Basdavanos shared her father’s journey with multiple shoulder, hip, and knee orthopedic pathologies that preceded his diagnosis of ATTR wild-type (ATTRwt). In the single center retrospective study performed under the guidance of Dr. Mazen Hanna at Cleveland Clinic, 1,310 amyloidosis cases were screened for orthopedic ailments. Overall, 24.7% of cases presented with shoulder pathologies, which were more common in ATTR than AL patients. Clinicians who routinely screen patients for bilateral carpal tunnel disease, spinal stenosis, or biceps tendon rupture should also include shoulder pathologies in their symptom review to strengthen suspicion of possible cardiac amyloidosis. This data could potentially be utilized for building institutional protocols to screen for amyloidosis at large.  

Utilization of Artificial Intelligence in the Diagnosis of Cardiac Amyloidosis 

The future is here! Dr. Surendra Dasari from the Mayo Clinic, Rochester MN, presented an artificial intelligence (AI) echocardiogram (ECHO) based model to diagnose cardiac amyloidosis. The Mayo Clinic team evaluated the ECHO-based AI model utilization alone as well as when utilized in junction with the standard 12-lead electrocardiogram (ECG) AI model they had already developed. Their echocardiogram variables had a very high predictive value for recognizing cardiac amyloidosis alone, and even higher when fused to the ECG-based model. These results have important implications as we work on improving early recognition of cardiac amyloidosis. 

Primary Results from APOLLO-B, A Phase 3 Study of Partisiran in Patients with TTR Cardiac Amyloidosis 

Dr. Mat Maurer from Columbia University ended the symposium with perhaps the most anticipated presentation. Partisiran inhibits synthesis of wild-type and variant (hereditary) TTR and is currently approved for the treatment of Amyloid Transthyretin Variant (ATTRv) polyneuropathy. APOLLO-B aimed to investigate the safety and efficacy of partisiran in patients with ATTR cardiomyopathy. The sample study contained 80% wild-type patients. Primary results after 12 months supported partisiran as a potential therapeutic option for TTR cardiomyopathy, demonstrating statistically significant improvements on functional capacity and health-related quality of life. Additionally, mortality trended favorably in the partisiran arm when compared to placebo. Partisiran also demonstrated an acceptable safety profile, with no cardiac safety concerns. Although both the efficacy and safety of partisiran will continue to be investigated in the APOLLO-B open label extension period, the preliminary findings showed a promising therapeutic option for ATTR patients with cardiomyopathy.  

Diflunisal Treatment for Hereditary Transthyretin Amyloidosis 

Diflunisal is a non-steroidal anti-inflammatory drug that is known to stabilize TTR preventing amyloid fibril formation and reducing organ deposition of TTR. Given the high side effect profile compared with other TTR therapies, Diflunisal has not been widely utilized in the ATTR cardiomyopathy population. However, as a result of the high cost of novel ATTR therapies, and the associated financial burden experienced by patients and their families, Diflunisal is being re-considered as a cost-effective option.  

An observational study in Sweden, DFNS-02, followed 33 patients enrolled from 2015 to 2021 for a 24-month period. Changes in neurological and cardiac performance, as well as nutritional status were evaluated. The primary and secondary endpoints were met with stable cardiac, neurological, and nutritional disease states. Overall, the trial supported the efficacy of Diflunisal for ATTRv amyloidosis patients with both polyneuropathy and cardiomyopathy, providing a treatment option to those patients unable to afford novel TTR therapies. Risk stratification for patient selection and longitudinal monitoring of adverse events should, however, always be considered when using Diflunisal therapy.  

Expanding Amyloidosis Care Around the World 

Global Bridge Health Care Alliance and its founding partner Mayo Clinic have created a global network of healthcare professionals to provide training and share diagnostic and treatment information around the world. As an underdiagnosed disease, Amyloidosis has become the focus of their work by joining resources to support multidisciplinary programs such as the Abdali Medical Center, Hospital das Clinicas, and Methodist Le Bonheur Healthcare, among others. Representatives from those institutions took the ISA stage to share their stories and their efforts to make Amyloidosis care available around the globe. They were perhaps the most touching and emotional of the presentations, demonstrating that although it takes a village to overcome global healthcare inequities, it is always possible when healthcare providers and non-profit organizations partner to make it happen! 

In light of significant progress made over the last decade, there is still much more to be done to improve patient outcomes and make Amyloidosis care equitable across the world. ISA 2022 has wrapped, but the partnerships formed and the knowledge shared during the symposium lay a foundation for further scientific advancements, disease management strategies, and pharmaceutical solutions to improve survival and quality of life on behalf of patients. We look forward to what ISA 2024 at Mayo Clinic in Rochester, MN will bring! 

For more information on ISA 2022 scientific sessions, please visit: https://www.isaheidelberg2022.org/scientific-program/