Mark A. Fiala

Washington University in St. Louis | WUSTL , Wash U · Division of Oncology

Background: Multiple myeloma (MM) is the most common hematologic neoplasm among African Americans (AA), who have a 1.5-2-fold excess compared to Whites. Older age, male sex and obesity are also established risk factors. There is a knowledge gap regarding the tumor microenvironment (TME) in MM, especially in AA's. It is important to understand the e...

Somatic mutation phasing informs our understanding of cancer-related events, like driver mutations. We generated linked-read whole genome sequencing data for 23 samples across disease stages from 14 multiple myeloma (MM) patients and systematically assigned somatic mutations to haplotypes using linked-reads. Here, we report the reconstructed cancer...

Multiple Myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We established a harmonized consortium to generate an Immune Atlas of MM aimed at inf...

PURPOSE Financial toxicity is a contributor to the psychosocial burden of cancer care. There is no consensus measure of financial toxicity; however, recent studies have adopted the Comprehensive Score for Financial Toxicity (COST). Despite its growing popularity, data on the responsiveness to change of the COST instrument are lacking. To address th...

Background Despite improvements in prevention and treatment, severe coronavirus disease 2019 (COVID-19) is associated with high mortality. Phosphoinositide 3-kinase (PI3K) pathways contribute to cytokine and cell-mediated lung inflammation. We conducted a randomized, placebo-controlled, double-blind pilot trial to determine the feasibility, safety,...

Background Clinical risk assessment scores, such as IMPEDE VTE, can identify patients with multiple myeloma (MM) at high-risk of venous thromboembolism (VTE). Refinement of these scores, by including 1 or more biomarkers, could improve risk assessment. Objectives We sought to determine the association between soluble P-selectin (sP-selectin) and D...

We performed a systematic review of the literature investigating the demographic and insurance-related factors linked to disparities in multiple myeloma (MM) care patterns in the United States from 2003 to 2021. Forty-six observational studies were included. Disparities in MM care patterns were reported based on patient race in 76% of studies (34 o...

Background: Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplant (allo-HCT). Azacitidine (AZA) is a hypomethylating agent that has been shown to be effective in preclinical and clinical studies for the prevention of acute GvHD (aGvHD). Objectives: We sought to determine the maximum tolerated dos...

Background: Multiple myeloma (MM), as well as some treatments for MM, increase the risk of venous thromboembolism (VTE). Prior literature suggests carfilzomib, lenalidomide, and dexamethasone (KRd) may have a higher incidence of thromboembolic events compared with bortezomib, lenalidomide, and dexamethasone (VRd). We aimed to evaluate VTE risk wit...

To the Editor The serum free light chains (sFLC) assay aids in the diagnosis, monitoring, and prognostication of monoclonal gammopathies (MGs) (1). Among MG’s, light chain monoclonal gammopathy of undetermined significance (LC-MGUS) is unique as it can be diagnosed when an abnormal sFLC ratio is the only evidence of a clonal plasma cell process (2,...

Introduction: Abiraterone and enzalutamide are treatments for metastatic castration-resistant prostate cancer (mCRPC). Due to a lack of head-to-head trials, they are prescribed interchangeably. However, the drugs have different pharmacokinetics and thus may have differing efficacy and adverse effects influenced by patient functional status and com...

Multiple myeloma (MM) is a cancer of older adults and those who are more frail are at high risk of poor outcomes. Current tools for identifying and categorizing frail patients are often static and measured only at the time of diagnosis. The concept of dynamic frailty (i.e. frailty changing over time) is largely unexplored in MM. In our study, adult...

Background: Serum free light chain (sFLC) assays are interpreted using a sFLC-ratio-based reference interval (manufacturer's interval) that was defined using a cohort of healthy patients. However, renal impairment elevates the sFLC-ratio, leading to a high false positive rate when using the manufacturer's interval. Prior studies have developed ren...

Purpose Financial toxicity is a contributor to the psychosocial burden of cancer care. There is no consensus measure of financial toxicity, however, recent studies have adopted the COmprehensive Score for financial Toxicity (COST). Despite its growing popularity, data on the responsiveness to change of the COST are lacking. To address this gap in t...

Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target disco...

Background: Zaccaria and colleagues recently proposed a new risk score to identify patients at high risk for relapse within 18 months of diagnosis (ER18), the Score for Early Relapse in Multiple Myeloma (S-ERMM). We performed external validation of the S-ERMM using data from the CoMMpass study. Patients and methods: Clinical data was obtained fr...

Purpose A utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM. Methods A qualitative study...

Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM’s progression is facilitated by complex interactions with the surrounding bone marrow (BM) cells, forming a microenvironment that supports tumor growth and drug resistance. Understan...

Introduction/background: People with multiple myeloma are at risk for financial toxicity due to the high cost of treatment and prolonged treatment duration. However, little data exist regarding financial toxicity among people with myeloma. Patients and methods: In this study, a cohort of 135 patients were recruited from an ongoing observational...

Multiple myeloma (MM) is a cancer of older adults with significant morbidity and mortality. Frail patients are a high-risk subgroup at risk for poor outcomes. While a number of tools have been developed for frailty assessment, many are measured only at baseline and do not take into account changes in frailty over time. Understanding both improvemen...

Importance Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with ca...

Patients with multiple myeloma (MM) who are treated with lenalidomide rarely develop a secondary B-cell acute lymphoblastic leukemia (B-ALL). The clonal and biological relationship between these sequential malignancies is not yet clear. We identified 17 patients with MM treated with lenalidomide, who subsequently developed B-ALL. Samples were evalu...

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow (BM) and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. Thus, TAMs have become an emerging target of interest. IL-10 is a k...

As part of the Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project, we compared immune cells of multiple myeloma bone marrow samples from 18 patients assessed by single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to understand the concordan...

Background: There remains an unmet need for molecularly targeted imaging agents in multiple myeloma (MM). The integrin, very late antigen-4 (VLA4), is differentially expressed in malignant MM cells as well as in the pathogenic inflammatory micro-environmental cells. [64Cu]Cu-CB-TE1A1P-LLP2A (64Cu-LLP2A) is a VLA4 targeted, high-affinity radiopharma...

People with multiple myeloma may be more susceptible to financial toxicity and its sequelae than other cancer types due to the high cost of treatment and its onset occurring typically late in life. However, little data exist regarding financial toxicity among people with myeloma. In this study, a cohort of 135 patients were recruited from an ongoin...

A first-degree relative (FDR) with colorectal cancer (CRC) is one of the most important risk factors for the disease. Adherence to CRC screening recommendations can help mitigate this risk; however, adherence has historically been low. This study aimed to determine the factors associated with CRC screening. The study used data from the 2015 Nationa...

Multiple myeloma (MM) is a cancer characterized by the unchecked proliferation of antibody-secreting plasma cells (PCs), which to date remains incurable despite therapeutic advancements. The idea that deeper tumor clearance leads to better outcomes is widely accepted in MM treatment: minimal residual disease (MRD) testing, whereby ultra-sensitive s...

Multiple Myeloma (MM) is a hematologic malignancy marked by uncontrolled clonal expansion of plasma cells. Previous research has examined single-cell transcriptome profiles of Monoclonal gammopathy of undetermined significance (MGUS) and MM tumor microenvironment (TME) and found that natural killer (NK) cell abundance is elevated in the early stage...

e19063 Background: Statins can inhibit cholesterol synthesis through inhibition of mevalonic acid synthesis, and reduce prenylation of proteins involved in tumor growth. Their anti-neoplastic potential has been explored for many malignancies (e.g., multiple myeloma) with improvement in progression free- and overall- survival. Preclinical data suppo...

e18762 Background: Prognostication of patients with myelodysplastic syndromes (MDS) using IPSS-R is not possible in administrative database analysis. In 2014, a claims-based prognostic scoring system, the SEER-Medicare MDS Risk Score (SMMRS) was developed to risk-stratify MDS patients for overall survival using ICD9 codes {Uno, 2014}. In 2015, ICD9...

Purpose In patients with multiple myeloma, characterizing adherence to orally administered therapies, such as lenalidomide, is critical given their frequent use and potential for poorer outcomes associated with nonadherence. However, little data exist using prospective measures of adherence in this population. Our study piloted use of Medication Ev...

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications,...

Introduction/Background This study aimed to describe patient and caregiver preferences for treatments of relapsed or refractory multiple myeloma (MM). Materials and Methods A survey including discrete-choice experiment (DCE) and best-worst scaling (BWS) exercises was conducted among US patients with relapsed or refractory MM and their caregivers....

Multiple myeloma (MM) is a cancer of bone marrow (BM) plasma cells, which is increasingly treatable but still incurable. In 90% of MM patients, severe osteolysis results from pathological interactions between MM cells and the bone microenvironment. Delineating specific molecules and pathways for their role in cancer supportive interactions in the B...

Importance The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective To quantify spatiotemporal variation in COVID-19 outc...

Background: Treatment-related financial burden, or financial toxicity, can detract from mental health and quality of life and can lead patients to alter their care to offset treatment costs. In doing so, these patients compromise adherence which can contribute to disparities (Zafar Oncologist 2013). Among cancers, multiple myeloma treatment is part...

Introduction: Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow (BM) and represents the second most common hematologic malignancy. Although therapeutic options have broadened over the years, the disease is challenged by frequent relapses. Relapsed/refractory MM (RRMM) often becomes non-responsive to previous lines of treatm...

Multiple Myeloma (MM) is the second most common hematologic malignancy, marked by uncontrolled clonal expansion of plasma cells. MM genome is complex and heterogeneous, with a high frequency of structural variants (SVs) and copy-number abnormalities (CNAs). Single-cell sequencing technologies offer advantages over traditional bulk methods in cancer...

Background: The Affordable Care Act (ACA) included many provisions that may have improved access to care for childhood cancer survivors (CCS). In this study, we sought to compare health insurance coverage and the affordability of health care among adult childhood CCS before and after the implementation of the ACA. Procedure: Using data from the...

Background : In the single-arm, phase 1b/2 CARTITUDE-1 study, ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen chimeric antigen receptor T-cell (CAR-T) therapy, showed encouraging efficacy in US patients with multiple myeloma (MM) who previously received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclona...

POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world expe...

Background Multiple myeloma (MM) is a cancer of plasma cells within the bone marrow (BM) and remains to be incurable. Tumor-associated macrophages (TAMs) are a major immunosuppressive component in the tumor microenvironment and display the pro-tumor M2 phenotype, supporting tumor proliferation, survival, and drug resistance. Targeting TAMs to block...

Background CD138 has been the gold-standard surface marker to detect multiple myeloma (MM) cells for decades; however, drug resistant minimal-residual disease (MRD) and circulating tumor cells (CTCs) were shown to have lower expression of this marker. We previously published that residual MM cells following treatment in vivo were hypoxic and the co...

Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is greatly desired. We have developed a novel patient-derived 3D tissue engineered bone marrow (3DTEBM) techno...

Mobilized peripheral blood has become the primary source of hematopoietic stem cells for both autologous and allogeneic stem cell transplantation. Granulocyte Colony-Stimulating Factor (G-CSF) is currently the standard agent used in the allogeneic setting. Despite the high mobilization efficacy in most donors, G-CSF requires 4-5 days of daily admin...

Purpose: To determine what factors are associated with colorectal cancer (CRC) screening adherence among first-degree relatives (FDRs) of people with CRC. Methods: The study used data from the 2015 National Health Interview Survey, a nationally representative survey in the US. Self-reported CRC screening rates were compared between FDRs and their p...

Importance COVID-19 is a life-threatening illness for many patients. Prior studies have established hematologic cancers as a risk factor associated with particularly poor outcomes from COVID-19. To our knowledge, no studies have established a beneficial role for anti–COVID-19 interventions in this at-risk population. Convalescent plasma therapy may...

Daratumumab, pomalidomide, and dexamethasone (DPd) is an FDA-approved 3rd or later line of therapy for myeloma. However, as there are limited published data on the efficacy of 2nd-line DPd, we conducted a retrospective analysis (n = 33). Herein, we report our center’s data for 2nd-line DPd. Our patient population had a high amount of high risk cyto...

Multiple myeloma (MM) is characterized by the uncontrolled proliferation of plasma cells. Despite recent treatment advances, it is still incurable as disease progression is not fully understood. To investigate MM and its immune environment, we apply single cell RNA and linked-read whole genome sequencing to profile 29 longitudinal samples at differ...

Carfilzomib, a next-generation proteasome inhibitor, improves outcomes in patients with multiple myeloma (MM); however, a proportion of those treated develop renal failure due to adverse event, comorbidity, or myeloma progression. The rate of renal failure and associated risk factors remains unknown in real-world populations. Adults with relapsed/r...

Plasma cell disorders including plasmacytomas and multiple myeloma (MM) are exquisitely radiosensitive, and thus, radiation therapy (XRT) is used effectively in their management. The role of XRT in the setting of novel MM therapeutics has not been explored. The 2016 National Cancer Database (NCDB) for MM with patients diagnosed between 2004 and 201...

Background Bortezomib is a common multiple myeloma therapy that can cause treatment-related peripheral neuropathy, a risk factor for falls. The relationship between bortezomib and falls in older patients with multiple myeloma is unknown. Methods We analyzed the SEER-Medicare database for patients aged 65 or older diagnosed with multiple myeloma be...

Objective To determine the association between scores from a 25-item patient-reported Rockwood Accumulation of Deficits Frailty Index (DAFI) and survival outcomes in gynecologic cancer patients. Methods A frailty index was constructed from the SEER-MHOS database. The DAFI was applied to women age ≥ 65 diagnosed with all types of gynecologic cancer...

Background: In multiple myeloma (MM), drug resistant cells underlie relapse or progression following chemotherapy. Cell adhesion mediated-drug resistance (CAM-DR) is an established mechanism used by MMC to survive chemotherapy and its markers are upregulated in residual disease. The integrin VLA4 (a4b1) is a key mediator of CAM-DR and its expressi...

Multiple myeloma (MM) is a hematological cancer of the antibody-secreting plasma cells. Despite therapeutic advancements, MM remains incurable due to high incidence of drug-resistant relapse. In recent years, targeted immunotherapies, which take advantage of the immune system's cytotoxic defenses to specifically eliminate tumor cells expressing cer...

Introduction: Currently, there are many 2nd-line treatment regimens for relapsed Multiple Myeloma (MM) but no standard therapy. Daratumumab, pomalidomide, and dexamethasone (DPd) is a newer 3-drug regimen approved by the FDA for treatment of multiple myeloma in the 3rd or later lines. The POLLUX trial reported a 12-month PFS of 83% in relapsed (med...

Introduction: Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). Thromboprophylaxis is a safe and effective way to decrease VTE in other high-risk populations. Recently, a clinical prediction model was developed to identify patients with newly diagnosed MM starting chemotherapy at hi...

Background Multiple myeloma (MM) is an incurable hematological malignancy of older adults. Autologous stem cell transplant (ASCT) remains a standard of care with multiple retrospective and registry cohort studies demonstrating its efficacy in MM patients including older adults with the disease. Despite this favourable data, there remains wide heter...

Carfilzomib is a critical chemotherapy medication used to treat patients with relapsed or refractory multiple myeloma. Unfortunately, drug-induced atypical hemolytic uremic syndrome (aHUS) has been established as a devastating and unpredictable side-effect of carfilzomib. Loss-of-function mutations in alternative complement pathway regulatory genes...