High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM) patients. Although outpatient ASCT has been shown to be safe and feasible, the procedure is overall rare with most patients in the US undergoing inpatient ASCT. Furthermore, hospitalization rates for patients that undergo outpatient ASCT remain high. Adequate markers that predict hospitalization during outpatient ASCT are lacking, yet would be of great clinical value to select patients that are suited to outpatient ASCT. In this study we aimed to elucidate differences between planned outpatient and inpatient ASCT and further evaluated clinical characteristics that are significantly associated with hospitalization during planned outpatient hospitalization. Factors that were significantly associated with a planned inpatient ASCT included an advanced MM disease stage, worse performance status as well as non-Caucasian race, while low albumin levels and female gender were significantly associated with hospitalization during outpatient ASCT. The results of this analysis provide crucial knowledge of factors that are associated with planned inpatient ASCT and hospitalization during outpatient ASCT and could guide the treating physician in decision-making and further facilitate outpatient transplantation.

[This corrects the article DOI: 10.1016/j.ahjo.2021.100075.].

Patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT) have become a critical treatment option in the treatment of many hematological malignancies, myeloproliferative disorders, and some solid tumors.Although HSCT has the potential of offering either a cure or minimizing disease burden while improving overall survival, HSCT is associated with some morbidity and mortality, particularly hypertension, diabetes, dyslipidemia, and renal disease with an increased cumulative incidence of cardiovascular (CVD) complications.Aside from the usual heart failure and arrhythmias, a less described complication is sinus tachycardia. The latter was once considered an innocuous finding in post-HSCT patients and mostly attributed to dehydration, low counts, deconditioning, chemotherapy, and/or infection.However, new data has shown that a number of these post-HSCT patients may harbor inappropriate sinus tachycardia, which can be associated with the eventual development of heart failure if not identified and treated.We believe that discussion of this topic not only is needed to raise awareness of this condition as patients might no longer be under the care of their oncologists but, most importantly, could be seen at any age, and general health practitioners might otherwise not be aware of this literature.

“The show must go on” Proverbial—initially applied to the United States 1876 centennial celebrations and originally printed in The Morning Republican (Scranton, PA) on 13 December 1875. No other ti...

Carfilzomib, a second-generation irreversible proteasome inhibitor, is currently considered the preferred therapy for relapsed and refractory multiple myeloma. There are several cardiovascular adverse effects described with carfilzomib chemotherapy most commonly being hypertension, dyspnea and decreased cardiac ejection fraction. We report a case of newonset pulmonary hypertension with right ventricular (RV) heart failure in a patient receiving carfilzomib. Awareness of this rare side effect of this drug is essential for prompt diagnosis and management. We also propose close monitoring of RV and pulmonary artery pressures along with left ventricular function in echocardiographic assessment in patients with carfilzomib chemotherapy.

Introduction - Despite improvement in Multiple Myeloma (MM) therapy, most patients will eventually experience disease relapse. The course of relapsed MM can be quite heterogeneous with some patients achieving long-term disease control while others experience rapid successive relapses with short survival. Other than genetic features, there is currently a lack of prognostic markers to guide intensity and duration of therapy in relapsed MM. In the present study, we elucidate the prognostic value of minimal residual disease (MRD) and focal lesion assessment by PET-CT in relapsed patients. Methods- We investigated 120 MM patients that were diagnosed between 2000-2016 and treated on our Total Therapy (TT) 2-6 protocols, which incorporated multi-agent chemotherapy and tandem transplantation. All 120 patients had achieved a complete remission (CR) after TT and relapsed subsequently after a median of 5 years (0.9-18). Focal lesions were assessed with PET-CT in 112 patients at diagnosis and relapse. Other features investigated included gene expression analysis (GEP) defined by the UAMS GEP70 at diagnosis and relapse (n=75) and FISH at diagnosis (n=84). Once treatment for relapsed disease was initiated, response to therapy, including sequential measurement of MRD by conventional 8 color flow cytometry with a sensitivity of 10-5 was assessed at least every 6-12 months. MM therapy after progression was directed by the treating physician and consisted mostly of combination therapy of a Proteasome Inhibitor with an IMiD and Dexamethasone (62%) or a Daratumumab combination (25%) or other (13%). Results- Median age at first progression was 65 years and median follow up time was post-relapse was 19 months (range 2.2-65 months). High risk FISH features, including deletion 17p, 1q amplification, t(4;14) and t(14;16) were present in 29% (25/84) of the patients, but were limited in predicting worse PFS post-relapse (p=0.3) and OS (p= 0.5); 75 patients had GEP performed at diagnosis and relapse showing a significant increase (p<0.01) of GEP70 defined high risk at relapse (36%, 26/75) compared to diagnosis (13%, 10/75). GEP70 defined high risk at relapse was significantly predictive of worse PFS (9 months vs 26 months; p=<0.01) and OS (22 months for vs not reached for GEP70 low risk; p<0.01). Focal lesions by PET-CT were found in 45% (50/111) of patients at relapse, 70% (35/50) of those had also focal lesions present at diagnosis. Similar to focal lesion assessment at diagnosis, the presence of at least 3 PET avid focal lesions at relapse confers worse PFS (Median PFS: 12 vs 25 months; p=0.1) and OS (median OS: 25 vs 52 months; p=0.05), albeit the results did not quite reach significance. Response assessment after initiation of treatment was as following: 51% (61/119) patients achieved a CR/sCR, 19% (23/119) achieved a VGPR, 14% (17/119) achieved a PR and 16% (19/119) achieved less than a PR. The achievement of MRD negativity (38%, n= 46/120) was a significant predictor of better PFS (NR vs 15 months; p=<0.01) and OS (NR vs 45 months, p=<0.01). Median time to the achievement of MRD negativity was 12.8 months (range: 1.9 to 36 months). Cox regression model showed that GEP70 defined risk (p<0.01, p<0.01), MRD assessment (p=0.02, p<0.01), age at progression (p=0.02, p<0.01) and the presence of at least 3 focal lesions by PET-CT (p=0.07, p<0.01) were most prognostic for worse PFS and OS in relapsed MM respectively. Time from initial diagnosis to first disease progression had a significant prognostic impact on PFS after first relapse (p=0.04), but not OS (p=0.35). Conclusion- Current clinical practice for relapsed MM incorporates mainly cytogenetic features that on their own seem to have limited predictive value. Our study suggests that risk classification and prognostication of relapsed MM can be significantly improved by using GEP and focal lesion assessment. Furthermore, achievement of MRD negativity should be the goal in relapsed MM therapy to improve clinical outcome. Disclosures van Rhee: EUSA: Consultancy; CDCN: Consultancy; Karyopharm: Consultancy; Adaptive Biotech: Consultancy; Takeda: Consultancy.

Artificial intelligence (AI)-based applications have found widespread applications in many fields of science, technology, and medicine. The use of enhanced computing power of machines in clinical medicine and diagnostics has been under exploration since the 1960s. More recently, with the advent of advances in computing, algorithms enabling machine learning, especially deep learning networks that mimic the human brain in function, there has been renewed interest to use them in clinical medicine. In cardiovascular medicine, AI-based systems have found new applications in cardiovascular imaging, cardiovascular risk prediction, and newer drug targets. This article aims to describe different AI applications including machine learning and deep learning and their applications in cardiovascular medicine. AI-based applications have enhanced our understanding of different phenotypes of heart failure and congenital heart disease. These applications have led to newer treatment strategies for different types of cardiovascular diseases, newer approach to cardiovascular drug therapy and postmarketing survey of prescription drugs. However, there are several challenges in the clinical use of AI-based applications and interpretation of the results including data privacy, poorly selected/outdated data, selection bias, and unintentional continuance of historical biases/stereotypes in the data which can lead to erroneous conclusions. Still, AI is a transformative technology and has immense potential in health care.

Hypertension is a silent killer and is the leading preventable risk factor for premature death and disability worldwide. 1 According to the latest US Center for Disease Control (CDC) report, hypertension is prevalent in 29% of adults aged 20 and over, and the prevalence increases to 63% of subjects 60 years and over. 2 Several factors, including excess calorie intake, obesity, sedentary lifestyle, and physical and emotional stress, contribute to its rising prevalence to epidemic proportions around the world.It is well established that patients with both hypertension and diabetes are at much higher risk of atherosclerotic cardiovascular disease and chronic kidney disease, especially women. 3ffective blood pressure management has been shown to decrease the incidence of stroke, heart failure, major cardiovascular events, and all-cause mortality.Further, the reductions of stroke, major cardiovascular events, and cardiovascular death are all proportional to the reduction of systolic and diastolic blood pressure and independent of the class of antihypertensive medications. 4Unfortunately, healthcare disparities in hypertension management are staggering.According to a study by Mills et al. in 2010, 5 worldwide only 46.5% of adults with hypertension were aware of their condition, 36.9% were treated with antihypertensive medications, and only 13.8% had their blood pressure controlled.Predictably, awareness, treatment, and control of hypertension were low in low-and middle-income countries, leading to poor outcomes.Several strategies, including health promotion, education, and simplification of the antihypertensive drug regimen, may help in medication adherence and improved outcomes.

Bortezomib is one of the mainstay treatments for patients with multiple myeloma (MM) in front line, relapsed, refractory and maintenance phases. Peripheral neuropathy is one of the most common adverse effect associated with its use. Herein we report two cases of Guillain-Barre syndrome in newly diagnosed MM patients treated with Bortezomib. The patients were treated with high-dose intravenous immunoglobulins and plasmapheresis with improvement in their symptoms. GuillainBarre syndrome is a rare but serious adverse effect in newly diagnosed MM patients treated with Bortezomib. Immediate discontinuation of therapy and appropriate neurological work up should be initiated to confirm the diagnosis. It is prudent to recognize the association and avoid further Bortezomib therapy in these patients.

Therapeutic angiogenesis is a novel method to create endogenous bypass conduits around the occluded coronary arteries. After the success in animal studies, therapeutic angiogenesis has been studied in humans with ischemic heart disease not responding to (or in addition to) conventional treatments. The most commonly studied angiogenic cytokines are vascular endothelial growth factor, fibroblast growth factor and granulocyte colony stimulating factor. Delivery as a protein, or vector with gene encoding for specific protein have been tested in clinical trials. These cytokines, using a multitude of delivery routes ranging from direct intramyocardial transfer either from epicardial or endocardial side, intracoronary infusion, systemic administration via subcutaneous route, have been introduced to myocardial tissues. Small sample size phase I studies have shown promising results. But large sample size, controlled studies have failed to demonstrate any significant improvement in various clinical, radiographic and angiographic outcomes in ischemic heart disease patients. Angiogenesis is influenced by a multitude of variables including duration of exposure, type of vector and need for co-factor. They also vary based on the individual patient characteristics. Further studies accounting for these variables are needed to fully determine the potential of therapeutic angiogenesis in ischemic heart disease.

Introduction: Multiple myeloma is a malignant neoplasm characterized by plasma cell proliferation in blood and bone marrow. Approximately two-thirds of the patients with multiple myeloma are >65 years at the time of diagnosis. Patients in this age group often have co-existing cardiovascular diseases. Areas covered: The presence of multiple myeloma adds to the malady by direct deposition of amyloid protein in the heart or via toxicity of chemotherapeutic agents. Cardiac contractile dysfunction, arrhythmias and thromboembolic disorders are the main issues in the management of elderly patients with multiple myeloma. Expert commentary: Assessment of cardiac risk and functional status requires careful evaluation by history, physical examination and imaging studies such as echocardiography and magnetic resonance imaging. The management of cardiovascular disorders in the presence of multiple myeloma is difficult and poses a challenge for the internist, the oncologist, and the cardiologist alike. This review is an overview of the problem of cardiovascular risk in and management of elderly patients with multiple myeloma.

Central nervous system (CNS) nocardiosis is a recognised opportunistic infection in immunocompromised patients. Treatment involves prolonged institution of antibiotics, making oral agents a convenient and desired option. Unfortunately, devising an effective, well-tolerated antimicrobial for the duration required to treat CNS nocardiosis is challenging owing to treatment intolerance and toxicities. This report highlights myelosuppression-sparing treatment with an oral tedizolid-based regimen following a complicated course with standard agents. A 68-year-old female from Florida (USA) with low-risk lambda light chain multiple myeloma complicated by persistently low CD4 counts, absolute neutrophil counts and IgG levels presented 18 months after diagnosis with fever, pneumonia, new-onset atrial fibrillation, right-sided hemiparesis, encephalopathy and slurred speech. Magnetic resonance imaging (MRI) showed numerous ring-enhancing lesions, and blood cultures were positive for Nocardia farcinica. The patient failed initial therapy with trimethoprim/sulfamethoxazole (SXT), linezolid and imipenem plus surgical debridement of the frontal lobe abscess. Intraoperative cultures were positive for N. farcinica. The treatment course was also complicated by steadily declining white blood cell and platelet counts despite receiving filgrastim. She was therefore placed on SXT and tedizolid for 6 months. Subsequent brain MRI showed complete resolution of the lesions and thus chemotherapy for multiple myeloma was re-initiated. In conclusion, tedizolid-based regimens may be an option for patients with myelosuppression requiring prolonged antibiotic therapy for CNS nocardiosis.

Autologous hematopoietic stem cell transplant (AHSCT) is the standard of care in the treatment of multiple myeloma worldwide. Infections are one of the most common complications of the chemotherapy regimen and AHSCT. Thrombotic microangiopathies are one of the rare but potentially life-threatening complications of infections associated with AHSCT. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (HUS) are two most common type of thrombotic microangiopathies. The HUS is classically related to diarrheal illness such as with E. coli strain O157: H7 that produce Shiga-like toxins. But it has never been described with Enterococcus raffinosus urinary tract infections (UTI). Here we are describing a case of atypical HUS associated with Enterococcus raffinosus UTI in a patient with multiple myeloma after AHSCT. The management of atypical HUS especially after AHSCT is challenging. Eculizumab, a humanized monoclonal antibody against complement protein C5, and thrombomodulin have emerging role in the management of some cases, but more studies are needed to define evidence-based management of this condition.

Introduction: Treatment options for patients with high-risk multiple myeloma (HRMM) are limited due refractoriness of the disease to established anti-myeloma agents and represent a very challenging population. Nivolumab (NIVO) is an IgG4 anti-PD-1 checkpoint inhibitors which is already FDA-approved for treatment of inoperable or metastatic melanoma, and several other highly advanced and metastasized solid and hematologic malignancies. NIVO binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen presenting cells (APCs). Activated PD-1 negatively regulates T-cell activation and plays an essential role in tumor evasion from host immunity. In this study we analyze the impact of NIVO in highly advanced, refractory HRMM. Methods: We retrospectively analyzed the efficacy and clinical outcome of NIVO in 12 refractory, heavily pretreated HRMM patients who were treated in our institute between March 2015 and September 2016. NIVO was given intravenously at 3 mg/kg every 2 weeks or 3 weeks as single agent or in combination with immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), daratumumab (DARA), ipilimumab (IPI), and dexamethasone (DEX), respectively. Adverse events were documented by chart review and response rates were assessed as per IMWG criteria. Results: The median age of patients was 61.5 years (range 42 -72) with 33% females. The median time from diagnosis to NIVO treatment was 8 years. Isotypes included 3 IgG, 4 IgA, 3 light chain, 1 non-secretory, and 1 bi-clonal (IgG K + IgM L) cases. All patients had HRMM defined by UAMS GEP risk score, 5 patients had HRMM at baseline, and 7 patients developed HRMM with progression of the disease. All patients had FDG-PET active and MRI DWIBS/STIR defined bone lesions. 75% (n=9) had documented extramedullary disease defined by FDG-PET. All patients have been treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) in the past with a median of 3 ASCT (range 1 - 5). The median number of prior lines of therapy was 6 (range 2 - 13). All patients were refractory to bortezomib (BTZ) and thalidomide (THA), 92% to carfilzomib (CFZ) and lenalidomide (LEN), 67% to pomalidomide (POM), 50% to DARA. NIVO was used as single agent (n=4), in combination with IMiDs+PIs+DEX (n=2), IMiDs + DEX (n=2), IPI (n=1), IPI+IMIDs (n=1), IMiDs-PIs-DARA-DEX (n=1), and IMiDs+DARA (n=1), respectively. All patient received a dose of 3 mg/kg, except 1 patient who received 1 mg/kg. In median 2 cycles (range 1 - 9) were applied every 2 weeks (n=6) or 3 weeks (n=2). The overall response rate (ORR) was 17%. 75% showed clinical benefit (2 PR, 2 MR, 5 SD), 25% had progressive disease. Those 2 patients who revealed PR have been on regimen consisting of NIVO+LEN+CFZ+DEX and NIVO+POM+CFZ+DARA+DEX. The 2 patients who demonstrated MR were on NIVO+POM+DEX and NIVO+LEN+CFZ+DEX. No response was seen in those patient who only received single agent NIVO. The median PFS was 5 weeks. The median overall survival was 5 months. 67% (n=8) of the patients developed adverse events which included infections (n=4, sinusitis, pericarditis, pneumonitis, colitis), general weakness (n=5), orthostatic dysregulation (n=1) and joint and bone pain (n=1). Conclusion: NIVO can be safely applied in highly advanced, pretreated, refractory HRMM in combination with other established anti-myeloma agents. NIVO as single-agent was not effective in this heavily pretreated and immunocompromised myeloma population. NIVO in combination with IMiDs, PIs, DARA and DEX is revealing efficacy in highly pretreated and refractory HRMM. Further clinical studies are warranted in order to explore the efficacy of NIVO in combination with other anti-myeloma agents in earlier stages of HRMM, low-risk MM and less immunocompromised patients. Disclosures Davies: Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Bristol-Myers: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria. Morgan: Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers: Consultancy, Honoraria.

Primary plasma cell leukemia (pPCL) is a rare form of multiple myeloma (MM) that is characterized by aggressive behavior and short overall survival (OS) despite significant improvement in anti-MM therapy. Due to its low incidence of 1-2% of all MM patients, most previous studies reported only on a small number of pPCL patients and the physiopathology as well as best treatment approaches remain unclear. In order to improve outcome in this patient population it will be necessary to evaluate molecular mechanisms underlying pPCL, which could potentially serve as therapeutic targets. The goal of the present study was to address clinical parameters and survival in pPCL patients. We further analyzed molecular characteristics by gene expression analysis and exome sequencing with the aim to detect distinct markers in pPCL.