Article
Cardiac & Cardiovascular Systems
Jan M. Griffin, Mathew S. Maurer
Summary: Cardiac amyloidosis is a rare disease with limited therapeutic options, but advancements in diagnostic modalities and emerging therapies are challenging the traditional beliefs about its prognosis. Early recognition and prompt initiation of novel agents are crucial in improving the outcomes for patients with ATTR-CA.
TRENDS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Medicine, General & Internal
Courtney M. Campbell, Kathleen Zhang, Daniel J. Lenihan, Ronald Witteles
Summary: The article details the chronological development of therapies for transthyretin amyloidosis (ATTR), including important clinical trials and emerging treatment methods. These new therapies can improve the quality of life and lifespan of ATTR patients, with a bright future outlook for therapy improvements.
AMERICAN JOURNAL OF MEDICINE
(2022)
Article
Neurosciences
Luca Gentile, Massimo Russo, Marco Luigetti, Giulia Bisogni, Andrea Di Paolantonio, Angela Romano, Valeria Guglielmino, Ilenia Arimatea, Mario Sabatelli, Antonio Toscano, Giuseppe Vita, Anna Mazzeo
Summary: A study involving 18 patients with hATTR amyloidosis treated with patisiran showed overall clinical stabilization for most patients, with some cases experiencing mild to moderate improvements even in advanced disease stages. Analysis of NIS, NIS-LL, and Norfolk QOL-DN results indicated a potential 6-month latency period before treatment benefits become apparent.
Article
Clinical Neurology
Matthias Schilling
Summary: Hereditary transthyretin-related amyloidosis (ATTRv) is a rare and fatal disease caused by mutations in the transthyretin gene. Treatment options include TTR stabilizing drugs and active agents that interfere with mRNA levels. These treatments aim to prevent amyloid tissue deposition and organ dysfunction.
Article
Clinical Neurology
Thomas H. Brannagan, Teresa Coelho, Annabel K. Wang, Michael J. Polydefkis, Peter J. Dyck, John L. Berk, Brian Drachman, Peter Gorevic, Carol Whelan, Isabel Conceicao, Violaine Plante-Bordeneuve, Giampaolo Merlini, Laura Obici, Josep Maria Campistol Plana, Josep Gamez, Arnt Kristen, Anna Mazzeo, Luca Gentile, Arvind Narayana, Kemi Olugemo, Peter Aquino, Merrill D. Benson, Morie Gertz
Summary: Inotersen treatment for over 3 years slowed the progression of polyneuropathy associated with hATTR, with no new safety signals observed.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Andreas Thimm, Sara Oubari, Julia Hoffmann, Alexander Carpinteiro, Maria Papathanasiou, Peter Luedike, Lukas Kessler, Christoph Rischpler, Christoph Roecken, Isabel Diebold, Tienush Rassaf, Hartmut Schmidt, Christoph Kleinschnitz, Tim Hagenacker
Summary: Hereditary transthyretin amyloidosis is a rare and genetically heterogeneous systemic disease characterized by widespread tissue deposition. Timely diagnosis and treatment are crucial for preventing rapid disease progression.
Review
Medicine, General & Internal
D. Adams
Summary: Hereditary transthyretin amyloid neuropathies are rare diseases caused by a mutation of the transthyretin gene. The disease affects both peripheral somatic and vegetative damages, with variable age of onset. Diagnosis can be made through genetic testing or evidence of amyloid deposition, and management requires a multidisciplinary approach involving neurologists, cardiologists, and geneticists.
BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE
(2023)
Article
Clinical Neurology
Marco Luigetti, Giovanni Antonini, Andrea Di Paolantonio, Luca Gentile, Marina Grandis, Luca Leonardi, Alessandro Lozza, Fiore Manganelli, Anna Mazzeo, Roberta Mussinelli, Filomena My, Laura Obici, Elena Maria Pennisi, Marina Romozzi, Massimo Russo, Mario Sabatelli, Alessandro Salvalaggio, Matteo Tagliapietra, Stefano Tozza
Summary: This article presents the long-term outcomes of Italian ATTRv patients who received inotersen within an early-access program. The study found that inotersen has a favorable safety profile and that the severity of neurologic disease at baseline is the main factor associated with disease progression.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Meissane Benbrahim, Kelsey Norman, Vaishali Sanchorawala, Omar K. Siddiqi, David Hughes
Summary: Transthyretin (ATTR) amyloidosis is a multisystem disease with treatments like tafamidis, diflunisal, patisiran, and inotersen. Treatment selection is based on subtype and presence of cardiac or neurological manifestations, with investigational therapies ongoing. Additional considerations such as side effects, monitoring, and administration are outlined in this review.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Ulrika Thelander, Gunilla T. Westermark, Gunnar Antoni, Sergio Estrada, Alice Zancanaro, Elisabet Ihse, Per Westermark
Summary: This study found that the binding of skeletal probes to amyloid-containing hearts is due to the presence of tiny calcification clusters, which are not directly associated with amyloid fibrils. Therefore, bone scans can be considered surrogate markers of ATTR amyloid, but caution is needed when estimating amyloid load or disease progression.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Peter Gorevic, Jaclyn Franklin, Jihong Chen, Gautam Sajeev, Jessie C. H. Wang, Hollis Lin
Summary: Patisiran demonstrated greater treatment effects on neuropathy and quality of life than inotersen in patients with hATTR amyloidosis with polyneuropathy, showing significant improvements in mNIS+7, Norfolk QOL-DN, BMI, and PND score. The results were consistent and robust across different analyses and methods.
EXPERT OPINION ON PHARMACOTHERAPY
(2021)
Article
Biotechnology & Applied Microbiology
Jinkun Wen, Tianqi Cao, Jinni Wu, Yuxi Chen, Shengyao Zhi, Yanming Huang, Peilin Zhen, Guanglan Wu, Lars Aagaard, Jianxin Zhong, Puping Liang, Junjiu Huang
Summary: This study established a humanized mouse model to mimic TTR amyloidosis and compared the efficiency of reducing mutant protein expression using dual adeno-associated virus (AAV8)-mediated split SpCas9 and single AAV8-mediated Nme2Cas9 systems. The results showed that the single AAV-mediated Nme2Cas9 system was more effective in reducing mutant protein expression, providing proof of principle for gene therapy for TTR amyloidosis.
Review
Clinical Neurology
Antonia Carroll, P. James Dyck, Mamede de Carvalho, Marina Kennerson, Mary M. Reilly, Matthew C. Kiernan, Steve Vucic
Summary: Hereditary transthyretin amyloidosis (ATTRv) is a severe genetic disease that primarily affects the peripheral and autonomic nervous system, heart, kidney, and eyes. Misdiagnosis rates are high, leading to diagnostic delays and increased disability. Timely diagnosis is crucial due to the availability of effective treatments. This review highlights key advances in diagnostic techniques, management strategies, and biomarker development for disease progression in ATTRv.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Surgery
Hartmut H. Schmidt, Jonas Wixner, Violaine Plante-Bordeneuve, Francisco Munoz-Beamud, Laura Llado, Julian D. Gillmore, Anna Mazzeo, Xingyu Li, Seth Arum, Patrick Y. Jay, David Adams
Summary: This study evaluated the efficacy and safety of patisiran in patients with ATTRv amyloidosis with polyneuropathy progression following liver transplantation. The results showed that patisiran reduced serum TTR levels, improved neuropathy and quality of life, and stabilized disability and nutritional status. Most patients had normal liver function. Patisiran treatment was well tolerated.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Cardiac & Cardiovascular Systems
Steven Law, Melanie Bezard, Aviva Petrie, Liza Chacko, Oliver C. Cohen, Sriram Ravichandran, Olabisi Ogunbiyi, Mounira Kharoubi, Sashiananthan Ganeshananthan, Sharmananthan Ganeshananthan, Janet A. Gilbertson, Dorota Rowczenio, Ashutosh Wechalekar, Ana Martinez-Naharro, Helen J. Lachmann, Carol J. Whelan, David F. Hutt, Philip N. Hawkins, Thibaud Damy, Marianna Fontana, Julian D. Gillmore
Summary: This study observed 879 patients with ATTR-CM and found that patients with NAC ATTR Stage Ia disease had significant cardiovascular morbidity despite good short- and mid-term survival. The concentration of NT-proBNP and diuretic requirement at diagnosis can be used to further stratify patients with NAC ATTR Stage I ATTR-CM.
EUROPEAN HEART JOURNAL
(2022)
Article
Hematology
Sarah Goldman-Mazur, Alissa Visram, Prashant Kapoor, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Suzanne R. Hayman, David Dingli, Taxiarchis Kourelis, Wilson Gonsalves, Rahma Warsame, Eli Muchtar, Nelson Leung, Moritz Binder, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Summary: It is unclear whether initiating therapy at the time of biochemical progression (BP) improves outcomes compared with initiating therapy at the clinical progression (CP) stage in patients with relapsed MM. This retrospective study found that patients with BP had longer time from second-line treatment to the next treatment and longer overall survival from first relapse. Male sex, plasma cell labeling index >= 2%, and extramedullary disease at diagnosis were associated with higher risk of CP, while very good partial remission or better decreased the risk of CP.
Article
Biophysics
Charalampos Charalampous, Utkarsh Goel, Morie Gertz, Martha Lacy, Angela Dispenzieri, Suzanne Hayman, David Dingli, Francis Buadi, Prashant Kapoor, Taxiarchis Kourelis, Rahma Warsame, William J. Hogan, Shaji Kumar
Summary: This study examined the impact of the time interval between the end of induction therapy and autologous hematopoietic transplantation on the survival of multiple myeloma patients. The results showed that a shorter interval was associated with a longer progression-free survival, particularly for patients with a partial response during induction.
BONE MARROW TRANSPLANTATION
(2023)
Editorial Material
Oncology
Jean-Sebastien Claveau, David L. Murray, Angela Dispenzieri, Prashant Kapoor, Moritz Binder, Francis Buadi, David Dingli, Amie Fonder, Morie Gertz, Wilson Gonsalves, Suzanne Hayman, Miriam Hobbs, Yi Lisa Hwa, Taxiarchis Kourelis, Martha Lacy, Nelson Leung, Yi Lin, Rahma Warsame, Robert A. Kyle, Vincent Rajkumar, Shaji K. Kumar
Letter
Oncology
Utkarsh Goel, Charalampos Charalampous, Prashant Kapoor, Moritz Binder, Francis K. Buadi, David Dingli, Angela Dispenzieri, Amie Fonder, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Miriam A. Hobbs, Yi L. Hwa, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Rahma M. Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
BLOOD CANCER JOURNAL
(2023)
Letter
Hematology
Morie Gertz
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Alissa Visram, Suzanne R. Hayman, Angela Dispenzieri, Prashant Kapoor, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, David Dingli, Rahma Warsame, Taxiarchis Kourelis, Joselle Cook, Moritz Binder, Wilson Gonsalves, Eli Muchtar, Nelson Leung, Vivek Roy, S. Vincent Rajkumar, Shaji Kumar
Summary: Adding carfilzomib to high-dose melphalan conditioning prior to autologous stem cell transplantation shows promising efficacy and safety in patients with multiple myeloma who have received limited prior therapy.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shaji Kumar, Angela Dispenzieri, Divaya Bhutani, Morie Gertz, Ashutosh Wechalekar, Giovanni Palladini, Raymond Comenzo, Rafael Fonseca, Arnaud Jaccard, Efstathios Kastritis, Stefan Schoenland, Charles la Porte, Huiling Pei, NamPhuong Tran, Giampaolo Merlini
Summary: This study analyzed the impact of cytogenetic abnormalities on the prognosis of patients with amyloid light-chain (AL) amyloidosis. The results showed that treatment with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) improved hematologic and organ response in all cytogenetic subgroups. Therefore, regardless of cytogenetic abnormalities, D-VCd can be considered as the standard of care for newly diagnosed AL amyloidosis.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Letter
Oncology
Saurabh Zanwar, Jithma P. Abeykoon, Stephen M. Ansell, Morie A. Gertz, Michelle Mauermann, Thomas E. Witzig, Patrick Johnston, Robert A. Kyle, Rebecca L. King, Thomas M. Habermann, Shaji Kumar, Prashant Kapoor
LEUKEMIA & LYMPHOMA
(2023)
Review
Oncology
Natalia Kreiniz, Morie A. Gertz
Summary: Smoldering multiple myeloma (SMM) is an asymptomatic condition with varying risks of progression. Risk stratification models like Mayo-2018 and IWWG are commonly used, and the personalized risk assessment tool PANGEA has been introduced. New markers, including genomic and immune characteristics, are being investigated for SMM progression. Treatment strategies for high-risk SMM have shown promising results, but adverse effects may occur in asymptomatic patients. This review aims to provide a comprehensive understanding of SMM progression risk.
LEUKEMIA & LYMPHOMA
(2023)
Article
Oncology
Nadine H. Abdallah, Alexandra N. Smith, Susan Geyer, Moritz Binder, Patricia T. Greipp, Prashant Kapoor, Angela Dispenzieri, Morie A. Gertz, Linda B. Baughn, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, David Dingli, Yi L. Hwa, Yi Lin, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Summary: This study aimed to estimate conditional survival (CS) at 1-8 years from diagnosis and investigate the impact of baseline prognostic factors on CS in multiple myeloma (MM) patients. A retrospective study including 2556 MM patients diagnosed between 2004 and 2019 was conducted. The findings revealed that age ≥65 and proteasome inhibitor+immunomodulatory-based induction were associated with decreased and increased survival, respectively, retained at 5 years. High-risk cytogenetic factors had a significant adverse impact at 1 and 3 years but not 5 years. Chromosome 17 abnormality was associated with decreased survival only at 1 year. Overall, the 5-year CS remained stable at 1-5 years from diagnosis among MM patients, and the prognostic impact of high-risk cytogenetic factors decreased with additional years survived.
BLOOD CANCER JOURNAL
(2023)
Article
Hematology
Charalampos Charalampous, Utkarsh Goel, Prashant Kapoor, Moritz Binder, Francis K. Buadi, Joselle Cook, David Dingli, Angela Dispenzieri, Amie L. Fonder, Morie A. Gertz, Wilson Gonsalves, Suzanne R. Hayman, Miriam A. Hobbs, Yi L. Hwa, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Rahma Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Summary: Patients with multiple myeloma who do not respond to initial therapy have worse outcomes, and effective treatments for this population are lacking. This study found that early refractory disease is associated with shorter survival, but salvage autologous stem cell transplantation may improve outcomes for these patients.
Editorial Material
Hematology
Iuliana Vaxman, Caroline Kaufman, Amir Lerman, Morie A. Gertz
Summary: This article discusses coronary microvascular angina caused by cardiac amyloidosis.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Morie A. Gertz, Adam D. Cohen, Raymond L. Comenzo, Efstathios Kastritis, Heather J. Landau, Edward N. Libby, Michaela Liedtke, Vaishali Sanchorawala, Stefan Schoenland, Ashutosh Wechalekar, Jeffrey A. Zonder, Giovanni Palladini, Jackie Walling, Spencer Guthrie, Christie Nie, Carol Karp, Yuying Jin, Gene G. Kinney, Giampaolo Merlini
Summary: The VITAL trial assessed the efficacy and safety of birtamimab in combination with standard of care in AL amyloidosis patients. Although no significant difference was observed in the overall results, a post hoc analysis showed significant improvement in survival time at month 9 for Mayo stage IV patients treated with birtamimab.
Letter
Hematology
Morie A. Gertz
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Morie A. Gertz
Summary: Immunoglobulin light chain amyloidosis is a clonal plasma cell disorder characterized by the deposition of fragments of immunoglobulin light or heavy chain in tissues. Clinical features vary depending on the organs involved and can include heart failure, nephrotic syndrome, hepatic dysfunction, neuropathy, and atypical smoldering myeloma or monoclonal gammopathy.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)