Vaishali Sanchorawala

Boston University | BU · Department of Medicine

In the phase 3 ANDROMEDA trial, patients treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) had significantly higher rates of organ and hematologic response compared with patients who received VCd alone. Here, we present patient-reported outcomes (PROs) from the ANDROMEDA trial. PROs were assessed through cycle 6 usin...

TPS8076 Background: Light chain (AL) amyloidosis is a progressive and typically fatal disorder caused by misfolded AL protein produced by plasma cells. Birtamimab is a monoclonal antibody designed to neutralize circulating soluble and deposited insoluble amyloid, thus promoting phagocytic clearance. In 2018, the phase 3 VITAL study in newly diagnos...

Background: β2-microglobulin amyloidosis was first described in the 1980s as a protein deposition disease associated with long-term haemodialysis. More recently, two inherited forms resulting from separate point mutations in the β2-microglobulin gene have been identified. In this report, we detail a novel β2M variant, P32L, caused by a unique dinu...

Light chain amyloidosis has come far with the first ever treatment to get regulatory approval in 2021. Daratumumab based regimes achieve deep hematologic and organ responses; offering a new therapeutic backbone. Early identification, correct fibril typing, challenges of the very advanced patient and lack of therapies to remove amyloid deposits rema...

With limited existing data on hereditary factors in light chain (AL) amyloidosis, we conducted a study of patients with plasma cell dyscrasias or lymphoproliferative disorders in their family history. Among 1621 patients, we identified 44 probands (2·7%) with 52 relatives affected. The most common disorders in family members were multiple myeloma (...

Background: The recent availability of disease-modifying therapies for hereditary transthyretin amyloid (ATTRv) amyloidosis warrants urgency for earlier diagnosis and timely identification of active disease state among genetic carriers. Methods: We reviewed clinical neurological data of all patients with ATTRv amyloidosis with initial visits at...

Rationale & Objective Test the feasibility of replacing 24-hr urine collection with a single voided urine protein-to-creatinine ratio (UPCR) in patients with AL amyloidosis. Study Design Retrospective study examining the correlation between 24-hr urine measurement and UPCR at various proteinuria levels using linear regression analysis with Pearson...

Adverse events affecting Black patients, including skin hyperpigmentation, may be overlooked using existing clinical trial data on lenalidomide. The objective of this systematic review is to characterize the representation of Black participants and rate of. skin hyperpigmentation in clinical trials. In this systematic review and pooled analysis of...

The survivorship needs of patients with light-chain (AL) amyloidosis are complex, as is the diagnosis and treatment itself. Early diagnosis is critical in improving patient outcomes; however, given the nonspecific nature of the symptoms, most patients with AL amyloidosis require evaluation by multiple specialists, resulting in significant delays in...

In the first phase 3 study in relapsed/refractory AL amyloidosis (TOURMALINE-AL1 NCT01659658), 168 patients with relapsed/refractory AL amyloidosis after 1–2 prior lines were randomized to ixazomib (4 mg, days 1, 8, 15) plus dexamethasone (20 mg, days 1, 8, 15, 22; n = 85) or physician’s choice (dexamethasone ± melphalan, cyclophosphamide, thalidom...

Daratumumab as a single agent (sDARA) or in combination with chemotherapies (cDARA) leads to impressive hematologic and organ responses in AL amyloidosis. However, predictive factors associated with outcomes, and optimal duration of therapy remain unclear. We analyzed 107 patients with AL amyloidosis treated with daratumumab between 2017 and 2020....

Objectives The goals of this study were to characterize myocardial composition during the active and remission phases of light-chain (AL) cardiac amyloidosis. Background Cardiac dysfunction in AL amyloidosis is characterized by dual insults to the myocardium from infiltration and toxicity from light chains during the active phase and by infiltrati...

AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High dose intravenous melphalan and autologous stem cell transplantation was developed for the treatment of AL amyloidosis in the early 1990s and was prompted by its success in multiple myeloma. This application has evolved significantly over the pa...

Background: Two prospective phase II studies evaluated the efficacy of the anti-CD38 monoclonal antibody Daratumumab as a single agent (sDARA) in patients with relapsed AL amyloidosis and reported impressive hematologic and organ response rates. However, both studies included small number of patients and in one study sDARA was administered for 6 cy...

Background Orthostatic hypotension due to autonomic dysfunction is a well-known complication of light chain (AL) amyloidosis, which can become progressively debilitating and difficult to manage. Treatment of the underlying plasma cell dyscrasia will eventually decrease further amyloid deposition. Management of orthostatic hypotension secondary to A...

Introduction Intravenous (IV) daratumumab has become a standard in the treatment of MM and AL amyloidosis largely due to its significant clinical benefit. Due to the high risk of infusion-related reactions (IRRs) prolonged infusion times are required at time of treatment initiation. These lengthy administrations can limit clinic capacity, require s...

Introduction: Ixazomib is an oral proteasome inhibitor (PI) that is currently approved to be administered once weekly in combination with lenalidomide (LEN) and dexamethasone in RRMM (Moreau et al N Eng J Med 2016; 374:1621-1634). As most patients are LEN refractory at the time of first relapse, pomalidomide-based regimens are commonly utilized due...

Introduction: Light chain (AL) amyloidosis is a plasma cell disease characterized by the deposition of insoluble amyloid fibrils into organs leading to organ dysfunction and death. The analysis at 6 and 12 months of the ANDROMEDA study (NCT03201965) showed that the addition of subcutaneous (SC) daratumumab to the standard of care combination of bor...

Introduction: Renal light chain (AL) amyloidosis typically manifests as proteinuria with or without renal failure and is associated with a risk of progression to renal replacement therapy (RRT). A significant reduction in circulating amyloidogenic light chain is needed to achieve a renal response. Current renal response criteria are binary defining...

Introduction: Binary cardiac response assessment using NT-proBNP is prognostic in light chain (AL) amyloidosis. Previous studies suggested that refining the criteria to multi-level cardiac responses improves prognostic prediction. We validate a graded cardiac response assessment tool in AL amyloidosis using NT-proBNP or BNP. Methods: In this retros...

Introduction Systemic immunoglobulin light chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits, most commonly in the heart and kidneys. Management of the disease relies primarily on off-label use of multiple myeloma therapies. No treatments are approved for AL amyloidosis in the relapsed/refractory setting. In the phas...

Background: Natural history studies, which describe changing disease outcomes under real-world clinical practice, can help support drug development for rare diseases by defining appropriate endpoints for clinical trials. The current study provides natural history information on survival and mortality in light chain (AL) amyloidosis, a rare disease...

Background: Minimal residual disease (MRD) assessment can provide an index of robust disease control, particularly if MRD negativity is sustained over time. Whereas MRD status has well-established prognostic implications in multiple myeloma, its role in light chain (AL) amyloidosis-a related but biologically distinct plasma cell disorder-is present...

Background Binary cardiac response assessment using NT-proBNP is prognostic in light chain (AL) amyloidosis. Previous studies suggested that refining the criteria to multi-level cardiac responses improves prognostic prediction. We aimed to validate a graded cardiac response assessment tool in AL amyloidosis using NT-proBNP or BNP. Methods In this...

Background Renal light chain (AL) amyloidosis manifests as proteinuria with or without renal failure and is associated with a risk of progression to renal replacement therapy (RRT). A significant reduction in circulating amyloidogenic light chain is needed to achieve a renal response. Current renal response criteria are binary defining a renal resp...

The recent decades have ushered in considerable advancements in the diagnosis and treatment of systemic light chain (AL) amyloidosis. As disease outcomes improve, AL amyloidosis-unrelated factors may impact mortality. In this study, we evaluated survival trends and primary causes of death among 2337 individuals with AL amyloidosis referred to the B...

Background: Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. Methods: We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cy...

Background: Acute kidney injury (AKI) is a common complication after high dose melphalan and autologous stem cell transplantation (HDM/SCT) in patients with AL amyloidosis. However, its incidence, predictors and outcomes are not well known. Methods: This observational study included 223 patients with AL amyloidosis who underwent HDM/SCT. AKI was...

8003 Background: Systemic AL amyloidosis is a plasma cell disease characterized by the deposition of insoluble amyloid fibrils causing organ dysfunction and death. Primary results from the ANDROMEDA study showed that addition of subcutaneous (SC) daratumumab (DARA) to the standard of care combination of bortezomib, cyclophosphamide, and dexamethaso...

In a retrospective single-center review of patients with myeloma treated with the immunomodulatory drug thalidomide, lenalidomide, or pomalidomide, the authors report that marked hyperpigmentation occurred in 40% of Black patients, compared with 3.5% of White patients. Since only 2% of the participants in the original pivotal trial of lenalidomide...

Transthyretin (ATTR) amyloidosis is a multisystem disease caused by organ deposition of amyloid fibrils derived from the misfolded transthyretin (TTR) protein. The purpose of this article is to provide an overview of current treatment regimens and summarize important considerations for each agent. A literature search was performed with the PubMed d...

Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients r...

Background Hereditary transthyretin (hATTR) amyloidosis is a rare, systemic, progressive, and life-threatening disease in which transthyretin proteins misfold and aggregate as insoluble amyloid deposits, disrupting nervous, cardiac, gastrointestinal, and other organ tissues. There are limited available data about the experience of patients living w...

Background Atrial fibrillation (AF) during high-dose melphalan and autologous stem-cell transplantation (HDM/SCT) for light-chain (AL) amyloidosis confers significant morbidity. Traditional risk factors provide limited prediction for development of paroxysmal AF during this vulnerable period. Objectives We sought to assess the association of clini...

In marked contrast to multiple myeloma, racial/ethnic minorities are underrepresented in publications of systemic light-chain (AL) amyloidosis. The impact of race/ethnicity is therefore lacking in the narrative of this disease. To address this gap, we compared disease characteristics, treatments, and outcomes across racial/ethnic groups in a referr...

Introduction: Treatment of relapsed and refractory multiple myeloma (RRMM) continues to evolve as most patients are lenalidomide (LEN) refractory at the time of first relapse with its widespread use in both induction and maintenance therapy. Pomalidomide, bortezomib and dexamethasone in RRMM has demonstrated significant activity and improvement in...

Introduction Immunoglobulin light chain (AL) amyloidosis is a rare disease caused by a clonal plasma cell dyscrasia producing monoclonal light chains that misfold and form amyloid fibrils which can deposit in a variety of tissues and organs. This deposition of amyloid fibrils can lead to progressive organ impairment, multi-organ failure, and death...

Introduction: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has become a global health crisis since it was first reported in December 2019. In a subset of infected subjects, pneumonia, multi-organ failure, and eventually death can occur. Frail patients and those with comorbidities are believed to be at increased risk of severe manifestatio...

Introduction Immunomodulatory drugs (IMiDs), particularly lenalidomide, are associated with adverse skin reactions most commonly rash, xeroderma, and pruritus. While multiple myeloma disproportionately impacts black patients, the clinical trials used for registration of these medications predominantly enrolled white patients. The incidence and seve...

Background: Isatuximab (SAR650984) is an IgG1k monoclonal antibody that binds with high affinity to CD38 expressed on plasma cells in AL amyloidosis. It has been shown to be efficacious and well tolerated in relapsed and refractory multiple myeloma as a single agent and in combination. Here we report on the preliminary results of a prospective mult...

Background: Systemic AL amyloidosis is a rare disease characterized by amyloid fibril deposits, most commonly in the heart and kidneys; there are currently no health authority-approved treatments. Therapies for the treatment of multiple myeloma (MM), including bortezomib, cyclophosphamide, and dexamethasone (VCd), have been shown to improve outcome...

Background: Racial/ethnic minorities have been underrepresented in most population-based studies of AL amyloidosis published to date. This observation stands in marked contrast to multiple myeloma, a closely related disorder with a twofold higher incidence among blacks vs. whites. Given the scarcity of information about health disparities in AL amy...

Systemic amyloidoses are a group of progressive and life-threatening rare diseases. Patients often feel overwhelmed by the complexities of symptoms, treatment options, and management of their care team. The Amyloidosis Appointment Companion (AAC) was created to help patients identify their goals of care, changes in their condition, as well as the c...

Background: Systemic AL amyloidosis is characterized by the deposition of insoluble amyloid fibrils produced by light chains synthesized by clonal CD38+ plasma cells. Combining daratumumab (DARA) with bortezomib, cyclophosphamide, and dexamethasone (VCd) has demonstrated significantly improved outcomes in patients with AL amyloidosis. The classific...

Introduction: High dose melphalan and autologous stem cell transplantation (HDM/SCT) results in deep and durable responses and prolonged survival in highly selected patients with systemic immunoglobulin light chain (AL) amyloidosis. HDM/SCT is offered to select patients >65 years but melphalan dose is often reduced due to concerns for tolerability...

Introduction Intravenous (IV) daratumumab has become a standard in the treatment of MM and AL amyloidosis largely due to its significant clinical benefit. Due to the high risk of infusion-related reactions (IRRs), it is associated with prolonged infusion times. These lengthy administrations can limit clinic capacity, require split dose infusions, i...

Objective: Systemic light-chain (AL) amyloidosis is an uncommon hematologic plasma cell dyscrasia that is becoming increasingly recognized. Therapeutic agents used in AL amyloidosis overlap with those used in multiple myeloma; however, differences in disease features change treatment efficacy and tolerance. Pharmacists must be cognizant of these d...

Background: Immunoglobulin light chain (AL) amyloidosis is a rare, multi-systemic disorder characterized by two disease processes: an underlying plasma cell dyscrasia that provides the source of pathologic light chains, and the resulting organ dysfunction caused by deposition of amyloid light chain fibrils. There are no FDA approved treatments for...

Hematologic complete response (hemCR) in AL amyloidosis requires absence of monoclonal protein by immunofixation electrophoreses (IFE) and normal serum free light chain ratio (FLCR). Recent literature suggests that an involved free light chain (iFLC) <20 mg/L or difference in free light chains (dFLC) <10 mg/L may more accurately predict outcomes af...

Purpose The clinical diagnosis of pulmonary involvement in individuals with systemic AL amyloidosis remains challenging. [¹⁸F]florbetapir imaging has previously identified AL amyloid deposits in the heart and extra-cardiac organs. The aim of this study is to determine quantitative [¹⁸F]florbetapir pulmonary kinetics to identify pulmonary involvemen...

Introduction Symptomology of AL amyloidosis can be vague, with a broad range of manifestations and potential etiologies. We sought to determine whether time from initial patient‐reported symptom onset to diagnosis was associated with survival. Methods The Boston University Amyloidosis Patient Database was queried for patients with AL amyloidosis w...

The proteasome inhibitor, bortezomib, has become a backbone for the first line treatment of patients with AL amyloidosis who are not eligible for high dose melphalan and stem cell transplantation. The presence of t(11;14), seen in up to 40–60% of patients with AL amyloidosis, may be associated with poorer response when treated with bortezomib based...

The SARS‐CoV‐2‐associated disease (COVID‐19) is primarily manifested as a respiratory tract infection but may affect and cause complications from multiple organ systems (cardiovascular, gastrointestinal, kidneys, hematopoietic and immune systems) while no proven specific therapy exists. The challenges associated with COVID‐19 are even greater for p...

8546 Background: The PI bortezomib is commonly used in first-line therapy of AL, but new therapies are needed that are tolerable in the context of multi-organ dysfunction and that, in RRAL, offer improved outcomes following prior bortezomib. Ixazomib is an oral PI, and in TOURMALINE-AL1, the first phase 3 trial conducted in RRAL, while the first pr...

e19375 Background: It is estimated that the U.S. will spend $370 billion in 2019 on pharmaceuticals and by 2020 the cost of cancer care will be approximately 158 billion. Cost containment strategies for high cost drugs are needed. There exists an opportunity to decrease overall cost related to bortezomib by switching patients to generic bortezomib....

Objectives The purpose of this study was to determine phenotypes characterizing cardiac involvement in AL amyloidosis by using direct (fluorine-18-labeled florbetapir {[¹⁸F]florbetapir} positron emission tomography [PET]/computed tomography) and indirect (echocardiography and cardiac magnetic resonance [CMR]) imaging biomarkers of AL amyloidosis....

Although no therapies are currently approved for light chain (AL) amyloidosis, cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is considered a standard treatment for newly diagnosed patients. Based on safety and efficacy of the anti-CD38 antibody daratumumab in multiple myeloma (MM), the phase 3 ANDROMEDA study is evaluating daratumumab-Cy...

Despite achieving a hematologic complete response after treatment, many patients with AL amyloidosis do not attain recovery of organ function and/or experience hematologic relapse. A persistent plasma cell clone producing amyloidogenic light chains at levels below the detection threshold of traditional serologic methods is hypothesized to impede or...

Introduction Multiple myeloma (MM) is the most common indication for high dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT). In addition, patients with immunoglobulin light-chain amyloidosis (AL), a related plasma cell disorder, often benefit from ASCT. Objectives: We aimed to compare baseline demographics, peri-transp...

Introduction Monoclonal Ig deposition disease (MIDD) frequently leads to kidney failure, and a large proportion of these patients would greatly benefit from kidney transplantation. However, data on kidney transplantation outcomes in MIDD are limited. Methods This was a retrospective analysis of long-term renal outcomes of 23 patients with MIDD, in...

PURPOSE No established treatments exist for relapsed/refractory systemic light-chain (AL) amyloidosis. Bendamustine has shown potential in the treatment of multiple myeloma. We conducted a phase II, multicenter trial to assess the efficacy and safety of bendamustine with dexamethasone (ben-dex) in patients with persistent or progressive AL amyloido...