Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"The impact of Post-Transplant doxycycline in AL amyloidosis - updated results after Long-Term follow up.","authors":"Nadine Abdallah,&nbsp;Angela Dispenzieri,&nbsp;Eli Muchtar,&nbsp;Francis K Buadi,&nbsp;Prashant Kapoor,&nbsp;Martha Q Lacy,&nbsp;Yi L Hwa,&nbsp;Amie Fonder,&nbsp;Miriam A Hobbs,&nbsp;Suzanne R Hayman,&nbsp;Nelson Leung,&nbsp;David Dingli,&nbsp;Ronald S Go,&nbsp;Yi Lin,&nbsp;Wilson I Gonsalves,&nbsp;Moritz Binder,&nbsp;Taxiarchis Kourelis,&nbsp;Rahma Warsame,&nbsp;Robert A Kyle,&nbsp;S Vincent Rajkumar,&nbsp;Morie A Gertz,&nbsp;Shaji K Kumar","doi":"10.1080/13506129.2022.2155809","DOIUrl":"https://doi.org/10.1080/13506129.2022.2155809","url":null,"abstract":"<p><strong>Introduction: </strong>The current treatment paradigm of AL amyloidosis lacks effective fibril-directed therapies. Doxycycline has been shown to have anti-fibril properties in preclinical models. In 2012, we reported that posttransplant prophylaxis with doxycycline was associated with improved survival compared to penicillin in patients with haematologic response. We provide here updated results after long-term follow up.</p><p><strong>Methods: </strong>We included 553 patients who underwent transplant between July 24^th, 1996, and June 24^th, 2014. Doxycycline 100 mg daily was used for prophylaxis in patients with penicillin allergy; since 2013, doxycycline was used as the standard for prophylaxis. Prophylaxis was typically continued for a year after transplant.</p><p><strong>Results: </strong>The median follow-up from transplant was 12.7 years. Doxycycline was used for prophylaxis in 33% of patients; the rest received penicillin. The median time to next treatment was 6.0 (95%CI; 4.4-8.8) years and 6.0 (95%CI; 4.9-7.1) years in the doxycycline and penicillin groups, respectively (<i>p</i> = .89). The median overall survival was 12.0 (95%CI: 11.0-19.6) years and 11.0 (95%CI: 9.6-12.7) years in the 2 groups, respectively (<i>p</i> = .17). There was a minimal trend towards improved survival with doxycycline among patients with ≥ very good partial response and among patients with organ response that was not statistically significant.</p><p><strong>Conclusion: </strong>After long-term follow-up, there is no clear evidence to support benefit of doxycycline in the post-transplant setting.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"261-267"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10045257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echocardiographic findings in subjects with an amyloidogenic apolipoprotein A1 pathogenic variant.","authors":"Daniela Tomasoni,&nbsp;Alberto Aimo,&nbsp;Marianna Adamo,&nbsp;Matilde Nardi,&nbsp;Carlo Mario Lombardi,&nbsp;Valentina Regazzoni,&nbsp;Maria Grazia De Angelis,&nbsp;Iacopo Fabiani,&nbsp;Giampaolo Merlini,&nbsp;Roberta Mussinelli,&nbsp;Laura Obici,&nbsp;Giorgia Panichella,&nbsp;Giuseppe Vergaro,&nbsp;Claudio Passino,&nbsp;Francesco Scolari,&nbsp;Stefano Perlini,&nbsp;Michele Emdin,&nbsp;Marco Metra","doi":"10.1080/13506129.2023.2190003","DOIUrl":"https://doi.org/10.1080/13506129.2023.2190003","url":null,"abstract":"<p><strong>Background: </strong>Very small case series of patients with apolipoprotein A1 (ApoA1) amyloidosis are available.</p><p><strong>Methods: </strong>We described the clinical and echocardiographic characteristics of individuals with the pathogenic <i>APOA1</i> variant Leu75Pro (p. Leu99Pro), referred for cardiac screening.</p><p><strong>Results: </strong>We enrolled 189 subjects, 54% men, median age 55 years (interquartile range 42-67), 39% with concomitant renal disease and 31% with liver disease. Median left ventricular ejection fraction was 60% (55-66). Overall, these subjects did not show overt diastolic dysfunction nor left ventricular (LV) hypertrophy. Age correlated with interventricular septal (IVS) thickness (<i>r</i> = 0.484), LV mass index (<i>r</i> = 0.459), E/e' (<i>r</i> = 0.501), and right ventricular free wall thickness (<i>r</i> = 0.594) (all <i>p</i> < 0.001). Some individuals displayed red flags for cardiac amyloidosis (CA), and 14% met non-invasive criteria for CA. Twenty-nine subjects died over 5.8 years (4.1-8.0), with 10 deaths for cardiovascular causes. Individuals meeting echocardiographic criteria for CA had a much higher risk of all-cause death (<i>p</i> = 0.009), cardiovascular death (<i>p</i> = 0.001), cardiovascular death or heart failure (HF) hospitalisation (<i>p</i> < 0.001). Subjects with both renal and liver involvement had a more prominent cardiac involvement, and shortest survival.</p><p><strong>Conclusions: </strong>Subjects with the <i>APOA1</i> Leu75Pro variant displayed minor echocardiographic signs of cardiac involvement, but 14% met echocardiographic criteria for CA. Subjects with suspected CA had a worse outcome.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"335-345"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased expression of S100A8/A9 in V30M related ATTRv amyloidosis.","authors":"João Moreira,&nbsp;Sofia Martins,&nbsp;Margarida Saraiva,&nbsp;Maria João Saraiva","doi":"10.1080/13506129.2023.2185755","DOIUrl":"10.1080/13506129.2023.2185755","url":null,"abstract":"<p><strong>Introduction: </strong>Hereditary Transthyretin Amyloidosis is a rare, progressive and life-threatening systemic disease with predominant peripheral and autonomic nervous system involvement caused by mutation of the transthyretin protein. The most common TTR mutation regarding to ATTRv is a substitution of a Methionine for a Valine at position 30 that predisposes TTR to form aggregates and fibrils.</p><p><strong>Methods: </strong>S100A8 protein levels were measured in plasma samples from ATTRV30M patients and healthy donors. Additionally, S100A8/9 levels were measured in Schwann cells after incubation with human WT or V30M TTR. Moreover, bone marrow derived macrophages of either genetic background were generated and the expression of S100A8/9 was measured in response to toll like receptors agonists.</p><p><strong>Results: </strong>S100A8/A9 mRNA levels are decreased in HSF V30M mice as compared with the WT. Moreover, S100A8 protein levels were found downregulated in plasma samples from ATTRV30M patients. Furthermore, we provide evidence for a dysregulated S100 expression by Schwann cells in response to TTRV30M and by mutated macrophages in response to toll like receptors agonists.</p><p><strong>Conclusion: </strong>The presence of TTRV30M impacts S100 expression, possibly contributing to the impaired immune activation of Schwann cells in nerves from ATTRV30M patients. This may be linked to the diminished immune cellular infiltration in these nerves, contributing in this way for the neuronal dysfunction present in the disease.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"327-334"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10418204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison between tafamidis and liver transplantation as first-line therapy for hereditary transthyretin amyloidosis.","authors":"Pierre Socie,&nbsp;Anouar Benmalek,&nbsp;Cécile Cauquil,&nbsp;Eve Piekarski,&nbsp;Ilias Kounis,&nbsp;Ludivine Eliahou,&nbsp;Antoine Rousseau,&nbsp;François Rouzet,&nbsp;Andoni Echaniz-Laguna,&nbsp;Didier Samuel,&nbsp;David Adams,&nbsp;Michel S Slama,&nbsp;Vincent Algalarrondo","doi":"10.1080/13506129.2023.2177986","DOIUrl":"https://doi.org/10.1080/13506129.2023.2177986","url":null,"abstract":"<p><strong>Background: </strong>By stabilizing transthyretin, tafamidis delays progression of amyloidosis due to transthyretin variant (ATTRv) and replaced liver transplantation (LT) as the first-line therapy. No study compared these two therapeutic strategies.</p><p><strong>Methods: </strong>In a monocentric retrospective cohort analysis, patients with ATTRv amyloidosis treated with either tafamidis or LT were compared using a propensity score and a competing risk analysis for three endpoints: all-cause mortality, cardiac worsening (heart failure or cardiovascular death) and neurological worsening (worsening in PolyNeuropathy Disability score).</p><p><strong>Results: </strong>345 patients treated with tafamidis (<i>n</i> = 129) or LT (<i>n</i> = 216) were analyzed, and 144 patients were matched (72 patients in each group, median age 54 years, 60% carrying the V30M mutation, 81% of stage I, 69% with cardiac involvement, median follow-up: 68 months). Patients treated with tafamidis had longer survival than LT patients (HR: 0.35; <i>p</i> = .032). Conversely, they also presented a 3.0-fold higher risk of cardiac worsening and a 7.1-fold higher risk of neurological worsening (<i>p</i> = .0071 and <i>p <</i> .0001 respectively).</p><p><strong>Conclusions: </strong>ATTRv amyloidosis patients treated with tafamidis would present a better survival but also a faster deterioration of their cardiac and neurological statuses as compared with LT. Further studies are needed to clarify the therapeutic strategy in ATTRv amyloidosis.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"303-312"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel <i>APOA1</i> frameshift mutation Glu120Glyfs*60 with upper gastrointestinal involvement and an indolent course.","authors":"Eli Muchtar,&nbsp;Surendra Dasari,&nbsp;Jason D Theis,&nbsp;Laura Ongie,&nbsp;Huong T Cabral,&nbsp;Ellen D McPhail,&nbsp;Angela Dispenzieri,&nbsp;Morie A Gertz,&nbsp;Karen L Rech","doi":"10.1080/13506129.2023.2187679","DOIUrl":"https://doi.org/10.1080/13506129.2023.2187679","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"353-355"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10446124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors affecting the accuracy of amyloidosis identification and referral to a specialty centre.","authors":"Andrew Staron,&nbsp;Lisa M Mendelson,&nbsp;Tracy Joshi,&nbsp;Frederick L Ruberg,&nbsp;Vaishali Sanchorawala","doi":"10.1080/13506129.2023.2171787","DOIUrl":"https://doi.org/10.1080/13506129.2023.2171787","url":null,"abstract":"<p><strong>Objective: </strong>Diagnostic algorithms for amyloidosis have evolved over the past decade, particularly with the incorporation of imaging-based techniques to detect amyloid cardiomyopathy. We sought to identify the key sources of amyloidosis misidentification in the community, which lead to false positive referrals to a tertiary centre.</p><p><strong>Methods: </strong>We conducted a retrospective review of all referrals to the Amyloidosis Centre from 2010 to 2021 and identified cases lacking amyloid pathology upon final adjudication after extensive assessment at the centre. Factors for false positive referrals were examined.</p><p><strong>Results: </strong>Among 2409 referrals of suspected amyloidosis, 147 (6%) demonstrated an absence of amyloid pathology. This percentage increased over time from 4% in 2010 to 13% in 2021. False positive referrals consisted of more people of colour. The most frequent source of inaccuracy was the erroneous staining of tissue specimens with Congo red, followed by suggestive findings on cardiac imaging. In recent years, misinterpretation of ^99mtechnetium- pyrophosphate scintigraphy emerged as a major source of false positive referrals.</p><p><strong>Conclusion: </strong>Recognising these potential sources of diagnostic error in the workup of amyloidosis can improve patient care. Referral to a centre of excellence for amyloidosis helps confirm an accurate diagnosis and avoid mistreatment.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"297-302"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10399297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoglobulin light-chain amyloidosis mimicking bulbar amyotrophic lateral sclerosis.","authors":"Antoine Pegat,&nbsp;Emilien Bernard","doi":"10.1080/13506129.2022.2163891","DOIUrl":"https://doi.org/10.1080/13506129.2022.2163891","url":null,"abstract":"A 62-year-old man experienced involuntary weight loss (-36% in the last 6months) followed by dysphagia and dysphonia. He then developed painful and burning paresthaesia in his lower limbs. He also experienced progressive difficulty in walking due to postural dizziness. Clinical examination found an atrophic tongue with profuse fasciculations (Figure 1), few fasciculations in the four limbs, abductor pollicis brevis weakness, distal hypoesthesia in the four limbs, general areflexia, and neurogenic orthostatic hypotension. Nerve conduction studies and needle electromyography showed mixed axonal and demyelinating sensorimotor polyneuropathy, bilateral carpal tunnel syndrome, as well as widespread fasciculations and fibrillations in the bulbar, cervical, thoracic and lumbar regions. IgG lambda monoclonal immunoglobulin (2 g/L), elevated serum lambda/kappa ratio (10.4, N< 1.65) and bone marrow clonal plasma cell infiltration were found, along with tissue amyloid deposition of lambda light chains accessed by immunofluorescence staining of the minor salivary glands. The final diagnosis was immunoglobulin light-chain amyloidosis complicated by lower motor neuron dysfunction. After treatment (melphalan, ixazomib and dexamethasone, followed by daratumumab) all neurological signs/symptoms improved including bulbar signs despite the absence of complete hematological response. To our knowledge the case presented herein is the first of immunoglobulin light-chain amyloidosis with bulbar onset mimicking motor neuron disease at initial presentation. For the two patients with an initial diagnosis of motor neuron disease revealing an immunoglobulin light-chain amyloidosis described in the literature the first symptom was lower limb weakness [1,2]. However, patients with systemic amyloidosis disease are reported to present with bulbar signs but during the course of the disease [3]. Also, motor neuropathy with early-onset severe bulbar involvement has been described for familial amyloid neuropathy (due to mutations in TTR [4,5] or GSN (encodes gelsolin)) [6]. The present report highlights that bulbar signs mimicking bulbar amyotrophic lateral sclerosis could be the first manifestation of immunoglobulin light-chain amyloidosis and underlined that dedicated workup should be performed in all atypical motor neuron diseases associated with sensory abnormalities, neuropathic pain or autonomic dysfunction. Acknowledgments","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"346-347"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multicentric study of the disease risks and first manifestations in hereditary transthyretin amyloidosis (ATTRv): insights for an earlier diagnosis.","authors":"Violaine Planté-Bordeneuve,&nbsp;Farida Gorram,&nbsp;Malin Olsson,&nbsp;Intissar Anan,&nbsp;Anna Mazzeo,&nbsp;Luca Gentile,&nbsp;Eugenia Cisneros-Barroso,&nbsp;Juan Gonzalez-Moreno,&nbsp;Ines Losada,&nbsp;Marcia Waddington-Cruz,&nbsp;Luiz Felipe Pinto,&nbsp;Yeşim Parman,&nbsp;Pascale Fanen,&nbsp;Flora Alarcon,&nbsp;Gregory Nuel","doi":"10.1080/13506129.2023.2178891","DOIUrl":"https://doi.org/10.1080/13506129.2023.2178891","url":null,"abstract":"<p><strong>Background: </strong>In hereditary transthyretin amyloidosis (ATTRv), early manifestation and age at onset (AO) may vary strikingly. We assessed the disease'risk (penetrance), AO and initial features in ATTRv families to gain insights on the early disease presentation.</p><p><strong>Methods: </strong>Genealogical information, AO and first disease manifestations were collected in ATTRv families, from Sweden, Italy (Sicily), Spain (Mallorca), France, Turkey, Brazil. Penetrance was computed using a non-parametric survival method.</p><p><strong>Results: </strong>We analysed 258 TTRV30M kindreds and 84 carrying six other variants (TTRT49A, F64L, S77Y, S77F, E89Q, I107V). In ATTRV30M families, the earliest disease risk was found at age 20 years in the Portuguese and Mallorcan families and at age 30-35 years, in the French and Swedish groups. The risks were higher in men and in carriers of maternal descent. In families carrying TTR-nonV30M variants, the earliest disease risk ranged from 30 y-o in TTRT49A to 55 y-o in TTRI107V families. Peripheral neuropathy symptoms were the most frequent initial manifestations. Among patients carrying TTRnonV30M variants, about 25% had an initial cardiac phenotype, one third a mixed phenotype.</p><p><strong>Conclusion: </strong>Our work provided solid data on the risks and early features of ATTRv in a spectrum of families to enhance an early diagnosis and treatment.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"313-320"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10418213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steep increase in the number of transthyretin-positive cardiac biopsy cases in Japan: evidence obtained by the nation-wide pathology consultation for the typing diagnosis of amyloidosis.","authors":"Hironobu Naiki,&nbsp;Aina Yamaguchi,&nbsp;Yoshiki Sekijima,&nbsp;Mitsuharu Ueda,&nbsp;Kenichi Ohashi,&nbsp;Kinta Hatakeyama,&nbsp;Yoshihiko Ikeda,&nbsp;Yoshinobu Hoshii,&nbsp;Yukako Shintani-Domoto,&nbsp;Aya Miyagawa-Hayashino,&nbsp;Hanako Tsujikawa,&nbsp;Jin Endo,&nbsp;Tomio Arai,&nbsp;Yukio Ando","doi":"10.1080/13506129.2023.2180334","DOIUrl":"https://doi.org/10.1080/13506129.2023.2180334","url":null,"abstract":"<p><strong>Background: </strong>In 2019, 2020 and 2022, the Japanese Government approved the use of tafamidis and two technetium-scintigraphies for transthyretin amyloid (ATTR) cardiomyopathy, and announced the patient criteria for tafamidis therapy. In 2018, we had started a nation-wide pathology consultation of amyloidosis.</p><p><strong>Objective: </strong>To reveal the impact of approval of tafamidis and technetium-scintigraphy on the diagnosis of ATTR cardiomyopathy.</p><p><strong>Methods: </strong>Ten institutes participated in this study on the pathology consultation of amyloidosis and shared rabbit polyclonal anti-κ_116-133, anti-λ_118-134, and anti-transthyretin_115-124 antibodies. Proteomic analysis was performed when the typing diagnosis by immunohistochemistry was unavailable.</p><p><strong>Results: </strong>Out of 5400 consultation cases received from April 2018 to July 2022, the type of amyloidosis by immunohistochemistry was determined in 4119 of the 4420 Congo-red positive cases. The incidences of AA, ALκ, ALλ, ATTR, Aβ2M and others were 3.2, 11.3, 28.3, 54.9, 0.6 and 1.8%, respectively. Out of 2208 cardiac biopsy cases received, 1503 cases were ATTR positive. There were 4.0 and 4.9 times more total cases and ATTR-positive cases, respectively, in the last 12 months as compared to the first 12 months.</p><p><strong>Conclusions: </strong>The approval of tafamidis and technetium-scintigraphy raised the awareness of ATTR cardiomyopathy, leading to an upsurge in ATTR-positive cardiac biopsy cases.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"321-326"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10111255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 1b dose-escalation study of carfilzomib in combination with thalidomide and dexamethasone in patients with relapsed/refractory systemic immunoglobulin light chain amyloidosis.","authors":"Sriram Ravichandran, Andrew Hall, Matthew Jenner, Mamta Garg, Bhuvan Kishore, Helen Lachmann, Julian Gillmore, Alexandra Pitchford, Jamie B Oughton, Shameem Mahmood, Sajitha Sachchithantham, Philip Hawkins, Sarah Brown, Ashutosh Wechalekar","doi":"10.1080/13506129.2023.2169124","DOIUrl":"10.1080/13506129.2023.2169124","url":null,"abstract":"<p><strong>Introduction: </strong>Proteasome inhibitors are the backbone of AL amyloidosis treatment - bortezomib being most widely used. Carfilzomib is a proteasome inhibitor licenced to treat multiple myeloma; autonomic and peripheral neuropathy are uncommon toxicities with carfilzomib. There is limited data on the use of carfilzomib in AL amyloidosis. Here, we report the results of a phase Ib dose-escalation study of Carfilzomib-Thalidomide-Dexamethasone (KTD) in relapsed/refractory AL amyloidosis.</p><p><strong>Results: </strong>The trial registered 11 patients from 6 UK centres from September 2017 to January 2019; 10 patients received at least one dose of trial treatment. 80 adverse events were reported from 10 patients in the 1^st three cycles. One patient experienced dose-limiting toxicity (acute kidney injury) at a dose of 45 mg/m^2, and another patient had a SAR (fever). Five patients experienced an AE ≥ grade 3. There were no haematologic, infectious, or cardiac AE ≥ grade 3. The overall haematological response rate (ORR) at the end of three cycles of treatment was 60%.</p><p><strong>Conclusion: </strong>Carfilzomib 45 mg/m² weekly can be safely given with thalidomide and dexamethasone. The efficacy and tolerability profile appears comparable to other agents in relapsed AL amyloidosis. These data provide a framework for further studies of carfilzomib combinations in AL amyloidosis.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"290-296"},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}