Role of Palliative Care in the Supportive Management of AL Amyloidosis-A Review.

Light chain amyloidosis is a plasma-cell disorder with a poor prognosis. It is a progressive condition, causing worsening pain, disability, and life-limiting complications involving multiple organ systems. The medical regimen can be complex, including chemotherapy or immunotherapy for the disease itself, as well as treatment for pain, gastrointestinal and cardiorespiratory symptoms, and various secondary symptoms. Patients and their families must have a realistic awareness of the illness and of the goals and limitations of treatments in making informed decisions about medical therapy, supportive management, and end-of-life planning. Palliative care services can thus improve patients' quality of life and may even reduce overall treatment costs. Light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by the excessive secretion of light chains by an indolent plasma cell clone that gradually accumulates in vital organs as amyloid fibrils and leads to end-organ damage. With progressive disease, most patients develop diverse clinical symptoms and complications that negatively impact quality of life and increase mortality. Complications include cardiac problems including heart failure, hypotension, pleural effusions, renal involvement including nephrotic syndrome with peripheral edema, gastrointestinal symptoms leading to anorexia and cachexia, complex pain syndromes, and mood disorders. The prognosis of patients with advanced AL amyloidosis is dismal. With such a complex presentation, and high morbidity and mortality rates, there is a critical need for the establishment of a palliative care program in clinical management. This paper provides an evidence-based overview of the integration of palliative care in the clinical management of AL amyloidosis as a means of reducing ER visits, rehospitalizations, and in-hospital mortality. We also discuss potential future collaborative directions in various aspects of clinical care related to AL amyloidosis.

Renal AL Amyloidosis: Updates on Diagnosis, Staging, and Management.

AL amyloidosis is caused by the excessive production of nonfunctional immunoglobulins, leading to the formation of amyloid fibrils that damage vital organs, especially the heart and kidneys. AL amyloidosis presents with non-specific symptoms such as fatigue, weight loss, numbness, pain, and nephrotic syndrome. Consequently, diagnosis is often delayed, and patients typically present with advanced disease at diagnosis. The Pavia renal staging model stratifies patients based on their likelihood of progressing to dialysis. Treatment with daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (i.e., Dara-CyBorD) was effective in inducing renal response in the landmark phase III ANDROMEDA trial and reducing early mortality. However, determining the most appropriate treatment regimen for relapsed or refractory cases remains a challenge due to various patient- and disease-related factors. Encouragingly, t(11:14) may be a positive indicator of therapy responses to the anti-BCL2 therapy venetoclax. Moreover, it is increasingly possible-for the first time-to clear AL amyloid fibrils from peripheral organs by leveraging novel anti-fibril immunotherapeutic approaches, although these medications are still under investigation in clinical trials. Given these advancements, this review provides a comprehensive overview of the current strategies for diagnosing, staging, treating, and monitoring AL amyloidosis, emphasizing renal involvement.

In-silico approaches to assessing multiple high-level drug-drug and drug-disease adverse drug effects.

INTRODUCTION: Pharmacovigilance plays a pivotal role in monitoring adverse events (AEs) related to chemical substances in human/animal populations. With increasing spontaneous-reporting systems, researchers turned to in-silico approaches to efficiently analyze drug safety profiles. Here, we review in-silico methods employed for assessing multiple drug-drug/drug-disease AEs covered by comparative analyses and visualization strategies. AREAS COVERED: Disproportionality, involving multi-stage statistical methodologies and data processing, identifies safety signals among drug-AE pairs. By stratifying data based on disease indications/demographics, researchers address confounders and assess drug safety. Comparative analyses, including clustering techniques and visualization techniques, assess drug similarities, patterns, and trends, calculate correlations, and identify distinct toxicities. Furthermore, we conducted a thorough Scopus search on 'pharmacovigilance,' yielding 5,836 publications spanning 2003 to 2023. EXPERT OPINION: Pharmacovigilance relies on diverse data sources, presenting challenges in the integration of in-silico approaches and requiring compliance with regulations and AI adoption. Systematic use of statistical analyses enables identifications of potential risks with drugs. Frequentist and Bayesian methods are used in disproportionalities, each with its strengths and weaknesses. Integration of pharmacogenomics with pharmacovigilance enables personalized medicine, with AI further enhancing patient engagement. This multidisciplinary approach holds promise, improving drug efficacy and safety, and should be a core mission of One-Health studies.

Efficacy and safety of idecabtagene vicleucel in patients with relapsed-refractory multiple myeloma not meeting the KarMMa-1 trial eligibility criteria: A real-world multicentre study.

Ide-cel received approval for relapsed-refractory multiple myeloma based on the results of the KarMMa-1 trial. However, patients with significant comorbidities, aggressive disease and prior B-cell maturation antigen-directed therapy (BCMA-DT) were excluded. This retrospective study evaluated real-world outcomes of patients who did not meet the KarMMa-1 eligibility criteria and were treated with standard of care (SOC) ide-cel. A total of 69 patients from three US centres who did not meet the KarMMa-1 criteria underwent ide-cel infusion. The main reasons for trial ineligibility included baseline grade 3-4 cytopenia (39%), prior BCMA-DT (26%), renal impairment (19%) and Eastern Cooperative Oncology Group performance status ≥2 (14.5%). Cytokine-release syndrome occurred in 81% vs. 84%, and immune effector cell-associated neurotoxicity syndrome occurred in 28% vs. 18% of SOC versus KarMMa-1 patients, respectively. Early infection (≤8 weeks post-infusion) and severe infection rates were 42% vs. 49% and 30% vs. 22% for the SOC versus KarMMa-1 cohorts, respectively. Grade 3-4 cytopenias for SOC versus KarMMa-1 cohorts were: neutropenia (87% vs. 89%), anaemia (51% vs. 60%) and thrombocytopenia (65% vs. 52%). Overall response rate was higher for the SOC cohort (93% vs. 73%), as was the complete response or better rate (48% vs. 33%). However, median progression-free survival and overall survival were comparable between the two groups. Our findings support broadening the inclusion criteria of future trials evaluating ide-cel.

Impact of Frailty on Outcomes after Chimeric Antigen Receptor T Cell Therapy for Patients with Relapsed/Refractory Multiple Myeloma.

The literature is limited regarding outcomes in older adults and frail patients receiving BCMA-directed chimeric antigen receptor T cell therapy (CAR-T) for relapsed or refractory multiple myeloma. Here we describe the safety and efficacy of CAR-T in these clinically important subgroups treated in a real-world setting. Frailty was defined as a frail score ≥2 using the simplified frailty index (score based on age + Eastern Cooperative Oncology Group [ECOG] Performance Status + Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI]). Of the 136 patients analyzed (age range, 41 to 81 years), 83 (61%) were considered frail at the time of CAR-T infusion. Compared to the nonfrail group, the frail group had higher proportions of patients with renal insufficiency (18% versus 6%), high-risk cytogenetics (45% versus 35%), extramedullary disease (51% versus 43%), and ECOG Performance Status ≥2 (18% versus 2%), and worse HCT-CI (3 versus 1). Although patients in the frail group had a higher incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) (39% versus 17%), the incidences of all- grade cytokine release syndrome (CRS), as well as high-grade CRS and ICANS, were similar in the 2 groups. With a median follow-up of 7 months, the median progression-free survival was 6.9 months in the frail group versus 11.1 months in the nonfrail group (P = .028). The median overall survival was 14 months in the frail group and was not reached in the nonfrail group (P = .025). This study highlights the tolerable safety and reasonable efficacy of CAR-T for frail myeloma patients in a real-world practice. Although the frail patients did not experience any excessive high-grade toxicities, they did have inferior efficacy outcomes.

Safety and Efficacy of Teclistamab in Patients with Relapsed/Refractory Multiple Myeloma: A Real-World Experience.

Teclistamab is a B cell maturation antigen (BCMA)-directed bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase I/II MajesTEC-1 trial. Here we report clinical outcomes with standard-of-care teclistamab in a real-world RRMM population. A total of 106 patients from 5 academic centers who received teclistamab from August 2022 to August 2023 were included in this retrospective analysis, 83% of whom would have been considered ineligible for the MajesTEC-1 trial. All patients were triple-class exposed, 64% were penta-class refractory, and 53% had received prior BCMA-directed therapy. Cytokine release syndrome was observed in 64% of patients, and only 1 event was grade ≥3, whereas immune effector cell-associated neurotoxicity syndrome was observed in 14% of patients (3 events were grade 3 or 4). One-third (31%) of patients experienced at least 1 infection, with nearly half of these infections graded as severe (grade ≥3). The overall response rate (ORR) was 66%, and the complete or better response rate was 29%. The ORR was 47% for patients with extramedullary disease (EMD), 59% for patients with prior BCMA-directed therapy exposure, and 68% for patients with penta-refractory disease. At a median follow-up of 3.8 months, the median progression-free survival (PFS) was 5.4 months (95% CI, 3.4 months to not reached), while median overall survival was not reached. Patients with Eastern Cooperative Oncology Group Performance Status ≥2, EMD, and age ≤70 years had inferior PFS on multivariable analysis. Our study demonstrates reasonable safety and good efficacy of teclistamab in patients with RRMM treated in a real-world setting.

Immunotactoid hepatopathy: A novel entity with histologically proven recurrence post liver transplantation.

Immunotactoid deposition is a rare fibrillary deposition disease that is primarily seen in the kidney and is associated with paraproteinemia. Here, we report a case of hepatic immunotactoid deposition in a 67-year-old male with a history of smoldering myeloma and chronic kidney disease who underwent liver transplantation for metabolic dysfunction-related cirrhosis. Immunotactoid deposition was first identified in the explanted liver and recurred in the allograft within only 7 weeks following transplantation, presenting as ascites with normal liver function tests. The patient's posttransplant course was complicated by proteinuria and renal failure requiring dialysis. Histologic examination of both native and allograft livers demonstrated pink amorphous material occupying sinusoidal spaces that were Congo-red negative and immunoglobulin M Kappa-restricted. Electron microscopy revealed characteristic deposits of electron-dense bundles of hollow microtubules with a 40 nm diameter within the sinusoids and space of Disse, consistent with immunotactoids. Therapy of the patient's underlying plasma-cell dyscrasia utilizing a daratumumab-based regimen showed decreased serum paraproteins, resolution of ascites, and improved kidney function, no longer requiring dialysis, without inducing rejection. The patient continues to respond to treatment 10 months posttransplant.

Analysis of risk factors and prognostic factors of brain metastasis in gastric cancer: a surveillance, epidemiology and end-results database study.

Brain metastasis in gastric cancer (GC) patients is a rare phenomenon that is associated with adverse clinical outcomes and poor survival rates. We conducted a retrospective cohort study to investigate the incidence, risk factors and prognostic factors of brain metastasis in GC patients. Data on sociodemographic and tumor characteristics of GC patients from 2010 to 2019 was extracted from the Surveillance, Epidemiology and End-Results (SEER) database. Descriptive statistics, multivariable logistic and Cox regression were applied on SPSS. Kaplan-Meier-Survival curves and ROC curves were constructed. A total of 59,231 GC patients, aged 66.65 ± 13.410 years were included. Brain metastasis was reported in 368 (0.62%) patients. On logistic regression, the risk of brain metastasis was significantly greater in males, patients aged < 60 years and patients having concurrent bone and lung metastasis. High grade and high N stage were significant risk factors for development of brain metastasis. Patients who had undergone surgery for the primary tumor were at reduced risk for brain metastasis (adjusted odds ratio 0.210, 95% CI 0.131-0.337). The median OS was 3 months in patients with brain metastasis and 17 months in patients without brain metastasis (p < 0.05). On Cox regression, Grade IV tumors and primary antral tumors were significant predictable parameters for poor prognosis. Overall Survival (OS) and Cancer-Specific Survival (CSS) were prolonged in patients who had undergone surgery. Brain metastasis in gastric cancer is associated with significantly worse survival. Employing large-scale screening for high-risk patients holds a promising impact to improve survival rates, but it must be accurately balanced with a comprehensive understanding of clinicopathological aspects for accurate diagnosis and treatment.

Interventional pain management in cancer patients-a scoping review.

BACKGROUND: Pain is the most prevalent symptom in cancer patients. To improve pain care, World Health Organization (WHO) Pain ladder was introduced in 1986 as a template for choosing pain medications in oncological settings. Since then, advancements in oncological treatments have improved the survival of cancer patients, requiring prolonged analgesia in various treatment stages. Additionally, there have been newer challenges in pain management with opioid epidemic and associated opioid use disorders. This has shifted the focus from WHO Pain Ladder and brought new importance to the rapidly evolving realm of interventional pain modalities for cancer pain management. This article reviews such interventional pain and minimally invasive neurosurgical options for pain management in cancer patients. METHODS: Systemic literature search in PubMed, Cochrane, and Embase. This included review articles, randomized controlled trials, non-randomized clinical trials (RCTs), and case series. RESULTS: A large array of interventional pain modalities are available for oncological pain management. These modalities carry relatively lower risk and provide effective analgesia while reducing concerns related to opioid use disorder. They target various areas in the anatomical and physiological pain pathways and provide more focused options for pain management at various stages of cancer and survivorship. Additionally, with improved sterile techniques, better imaging modalities, and growing technical and clinical expertise, interventional pain modalities offer a safe and often more efficacious method of pain management nowadays. Procedural modalities like intrathecal (IT) pumps, neuromodulation, kyphoplasty, and newer more targeted ablative techniques are now increasingly finding more roles and indications in cancer population. CONCLUSIONS: Interventional pain techniques are rapidly evolving and have become an integral part of cancer pain management. They can provide an additional option for cancer pain management, and can help reduce opioid consumption, and associated opioid side effects. With improvement in imaging modalities, procedural techniques, hardware, and infection control, they have a good safety profile and provide a rapid and efficacious approach for cancer pain management. This review articles aims to provide a basic understanding of various interventional pain modalities, their indications, efficacy, safety data, and associated complications.

Management of Adverse Reactions for BCMA-Directed Therapy in Relapsed Multiple Myeloma: A Focused Review.

Anti-B-cell maturation antigen therapies consisting of bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells have shown promising results in relapsed refractory multiple myeloma (RRMM). However, the severe side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia(s), infections, hemophagocytic lymphohistiocytosis, and organ toxicity, which could sometimes be life-threatening. This review focuses on these most common complications post-BCMA therapy. We discussed the risk factors, pathogenesis, clinical features associated with these complications, and how to prevent and treat them. We included four original studies for this focused review. All four agents (idecabtagene vicleucel, ciltacabtagene autoleucel, teclistamab, belantamab mafodotin) have received FDA approval for adult RRMM patients. We went through the FDA access data packages of the approved agents to outline stepwise management of the complications for better patient outcomes.

A Challenging Case of Kaposi Sarcoma Inflammatory Cytokine Syndrome.

Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS) is a serious, uncommon disease that occurs in patients who are positive for HIV and human herpesvirus-8 (HHV-8). It is characterized by a constellation of clinical findings, including fever, weight loss, and fluid retention, as well as a lack of multicentric Castleman disease (MCD) features on histopathology and an elevated serum HHV-8 viral load. Diagnosis is often delayed, and treatment options are limited, culminating in high mortality rates. We hereby present a 32-year-old male patient with HIV who was untreated for a few years and came with fever, night sweats, pancytopenia, and widespread adenopathy. A thorough evaluation of opportunistic infections was unremarkable. Clinically MCD was suspected, but lymph node biopsy only showed Kaposi sarcoma (KS) with no characteristic features of MCD. However, with clinical deterioration, KICS was strongly suspected. Kaposi sarcoma immune reconstitution syndrome (KS-IRIS) was also a possibility as the patient was restarted on antiretroviral therapy. Rituximab was commenced, but the patient suffered a cardiac arrest and could not be revived. Alternative diagnosis must be explored in patients with HIV presenting with constitutional symptoms, cytopenia, and adenopathy after opportunistic infections and malignancies are ruled out. If they have KS with HHV-8 positivity and there is a lack of characteristic features of MCD in lymph node biopsy, prompt suspicion of KICS should be made, and treatment with rituximab and/or chemotherapy should be instituted rapidly. KS-IRIS is also possible if patients have recently received antiretroviral therapy and have a rapid decline in viral load and increase in CD4 counts (immunological recovery). HHV8 viral load levels may help to distinguish between these two inflammatory conditions.

COVID-19 vaccine immune response in patients with plasma cell dyscrasia: a systematic review.

Background: Patients with plasma cell dyscrasia are at a higher risk of developing a severe Coronavirus-2019 (COVID-19) infection. Here we present a systematic review of clinical studies focusing on the immune response to the COVID-19 vaccination in patients with plasma cell dyscrasia. Objectives: This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to utilize the results to improve day-to-day practice. Design: Systematic Review. Methods: Online databases (PubMed, CINAHL, Ovid, and Cochrane) were searched following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Only articles published in the English language were included. Out of 59 studies, nine articles (seven prospective and two retrospective studies) were included in this systematic review. Abstracts, case reports, and case series were excluded. Results: In all nine studies (N = 1429), seroconversion post-vaccination was the primary endpoint. Patients with plasma cell disorders had a lower seroconversion rate compared to healthy vaccinated individuals and the overall percentage of seroconversion ranged between 23% and 95.5%. Among patients on active therapy, lower seroconversion rates were seen on an anti-CD38 agent, ranging from 6.5 up to 100%. In addition, a significantly lower percentage was recorded in older patients, especially in those aged equal to or greater than 65 years and those who have been treated with multiple therapies previously. Only one study reported a statistically significant better humoral response rate with the mRNA vaccine compared to ADZ1222/Ad26.Cov.S. Conclusion: Variable seropositive rates are seen in patients with plasma cell dyscrasia. Lower rates are reported in patients on active therapy, anti-CD38 therapy, and elderly patients. Hence, we propose patients with plasma cell dyscrasias should receive periodic boosters to maintain clinically significant levels of antibodies against COVID-19. Registration: PROSPERO ID: CRD42023404989.

COVID-19 vaccine immune response in patients with plasma cell dyscrasia- a systematic review Background: Patients with plasma cell disorders are at a higher risk of developing a severe coronavirus-19 infection. Here we present a systematic review of clinical studies focusing on the immune response to the coronavirus-19 vaccination in patients with plasma cell dyscrasia. Objectives: This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to transcribe the results to day-to-day practice. Design: Systematic Review Data sources: PubMed, CINAHL, Ovid, and Cochrane. Methods: Online databases were searched following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Only articles published in the English language were included. Abstracts, case reports, and case series were excluded. Out of 59 studies, nine articles were selected for a systematic review. Results: In all 9 studies (N = 1,429), seroconversion post-vaccination was the primary endpoint that our review assessed. Patients with plasma cell disorders had a lower seroconversion rate compared to healthy vaccinated individuals and the overall percentage of seroconversion ranged between 23 and 95.5%. Amongst patients on active therapy, lower seroconversion rates were seen in patients on an anti-CD38 agent, ranging from 6.5 up to 100%. In addition, a significantly lower percentage was recorded in older patients, especially those aged equal to or greater than 65 years and those who have been treated with multiple therapies previously. Only one study reported a statistically significant better humoral response rate with the mRNA vaccine compared to ADZ1222/Ad26.Cov.S. Conclusion: Variable seropositive rates are seen in patients with plasma cell dyscrasia. Lower rates are reported in patients on active therapy, anti-CD38 therapy, and elderly patients. Hence, we propose patients with plasma cell disorders should receive periodic boosters to maintain clinically significant levels of antibodies against COVID-19.

Ocular complications of antineoplastic therapies.

Ocular complications of antineoplastic agents can have a profound effect on the quality of life of cancer patients. New oncologic treatments like monoclonal antibodies, immunotherapies, antibody-drug conjugates, checkpoint inhibitors and growth factor receptors have resulted in increased ocular complications. These ocular complications differs in respect to distinct mechanisms of actions and lead to significant challenges in the management of cancer patients. In this review, we reviewed literature, clinical studies and cases detailing ocular complications due to administration of antineoplastic agents and emphasized the need for communication between oncologists and ophthalmologists toward early detection and management of ocular complications.

Ocular side effects can have a large impact on the quality of life on patients with cancer. New ways to treat cancer greatly increased patient prognosis, however, it has also resulted in increased ocular complications. This paper aims to review past medical literature, clinical studies, and case reports to describe the types of ocular complications that may arise from administration of antineoplastic agents. This paper emphasizes the need for communication between oncologists and ophthalmologists toward early detection and management for better patient care.

Toxicity Profile of Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapies in Multiple Myeloma: Pathogenesis, Prevention and Management.

Multiple myeloma is the second-most common hematologic malignancy in adults worldwide. Despite ongoing advancement in therapeutic modalities, it remains an incurable disease with a 5-year survival rate of approximately 50%. The recent development and introduction of anti-BCMA immunotherapies into clinical practice, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, has radically shifted the treatment paradigm. However, despite the promising potential of these therapies for broader application, frequent and significant adverse effects have been reported, both in short- and in long-term settings, requiring increasing awareness and vigilance in the treating team, close monitoring, and prompt interventions with a multidisciplinary approach. In this review, we will discuss the toxicities associated with CAR-T cell and bispecific antibody therapies, focusing on results from major clinical studies and real-world observations. In addition, we will emphasize on effective strategies for prevention, monitoring and management, and provide expert recommendations.

Systemic AL amyloidosis: current approach and future direction.

Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.

Management of Relapsed-Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice.

Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

Vasovagal Syncope and Pulseless Electrical Activity Cardiac Arrest in Patients With Immunoglobulin Light Chain Cardiac Amyloidosis: A Case Series.

Immunoglobulin light chain (AL) amyloidosis may lead to amyloid fibril deposition into peripheral and autonomic nerves, resulting in resting and orthostatic hypotension. While most patients die from progressive heart failure, the most commonly proposed cardiac rhythm associated with sudden death is pulseless electrical activity (PEA). Herein, we describe four patients with severe AL cardiac amyloidosis who had witnessed cardiac arrest with pulseless electrical activity as a result of vasovagal syncope. Healthcare providers should be aware of severe autonomic dysfunction in cardiac amyloidosis and the potential for an abnormal vasovagal response leading to syncope or death.

Advancements and future trends of immunotherapy in light-chain amyloidosis.

Light-chain (AL) amyloidosis is a type of plasma cell neoplasm with abnormal monoclonal immunoglobulin light-chain production and their subsequent deposition in tissues causing end-organ damage. In addition to existing treatments including autologous stem cell transplantation, there is a need for other approaches for eradicating abnormal plasma cells and amyloid tissue deposits. Treatment strategies of AL amyloidosis are mostly based on medications that are effective in multiple myeloma due to similar cell of origin. Daratumumab along with proteasome inhibitors and corticosteroids has become standard of care for AL amyloidosis. Another appealing approach is disassembling amyloid deposits with hope to potentially reverse the damage done by the disease. This was met with promising results for CAEL-101 and birtamimab. Although still in early stages, novel treatment options in pipeline, including antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor T cell therapy may diversify the treatment armamentarium of AL amyloidosis in the future.