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Disparidades en Atención de Salud , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/etnología , Mieloma Múltiple/epidemiología , Disparidades en Atención de Salud/etnología , Masculino , Femenino , Trasplante de Células Madre Hematopoyéticas , Persona de Mediana Edad , Accesibilidad a los Servicios de Salud , AncianoRESUMEN
PURPOSE: Patients with Waldenström macroglobulinemia (WM) have disparate outcomes. Newer therapies have emerged since the development of International Prognostic Scoring System, and MYD88L265P mutation is now frequently assessed at diagnosis, warranting reexamination of the prognostic parameters. PATIENTS AND METHODS: We reviewed records of 889 treatment-naïve patients with active WM, consecutively seen between January 01, 1996, and December 31, 2017, to identify clinical predictors of overall survival (OS) in univariate analyses. Patients with complete data for the parameters significant on the univariate analyses (n = 341) were included in a multivariable analysis to derive a prognostic model, subsequently validated in a multi-institutional cohort. RESULTS: In the derivation cohort (n = 341), age (hazard ratio [HR], 1.9 [95% CI, 1.2 to 2.1]; P = .0009), serum lactate dehydrogenase (LDH) above upper limit of normal (HR, 2.3 [95% CI, 1.3 to 4.5]; P = .007), and serum albumin <3.5 g/dL (HR, 1.5 [95% CI, 0.99 to 2.3]; P = .056) were independently prognostic. By assigning a score of 1 point each to albumin <3.5 g/dL (HR, 1.5) and age 66-75 years (HR 1.4) and 2 points for age >75 years (HR, 2.6) or elevated LDH (HR, 2.3), four groups with distinct outcomes were observed on the basis of the composite scores. Five-year OS was 93% for the low-risk (score 0), 82% for low-intermediate risk (score 1), 69% for intermediate-risk (score 2), and 55% for the high-risk (score ≥3; P < .0001) groups. In the validation cohort (N = 335), the model maintained its prognostic value, with a 5-year OS of 93%, 90%, 75%, and 57% for the four groups, respectively (P < .0001). CONCLUSION: Modified Staging System for WM (MSS-WM), utilizing age, albumin, and LDH is a simple, clinically useful, and externally validated prognostic model that reliably risk-stratifies patients with symptomatic WM into four groups with distinct prognosis.
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Macroglobulinemia de Waldenström , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/mortalidad , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Medición de Riesgo , Pronóstico , L-Lactato Deshidrogenasa/sangre , Estudios Retrospectivos , Anciano de 80 o más AñosAsunto(s)
Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Ciclofosfamida , Dexametasona , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Humanos , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Ciclofosfamida/administración & dosificación , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Femenino , Anciano , Insuficiencia del Tratamiento , Persona de Mediana EdadRESUMEN
The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n = 71), 51 progressed by last follow-up; the MDEs included: bone lesions (37%), anemia (35%), hypercalcemia (8%), and renal failure (6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression (14%), bone pain (20%), and hospitalization/ED presentations due to MM complications/symptoms (4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.
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Hipercalcemia , Mieloma Múltiple , Mieloma Múltiple Quiescente , Humanos , Mieloma Múltiple Quiescente/diagnóstico , Mieloma Múltiple Quiescente/terapia , Progresión de la Enfermedad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/epidemiología , Cadenas Ligeras de Inmunoglobulina , Factores de RiesgoRESUMEN
The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n=71), 51 progressed by last follow-up; the MDEs included: bone lesions(37%), anemia(35%), hypercalcemia(8%), and renal failure(6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression(14%), bone pain(20%), and hospitalization/ED presentations due to MM complications/symptoms(4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.
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Patients with multiple myeloma (MM) who do not respond to initial therapy have worse outcomes than primary responders, and effective treatments are lacking in this population. However, the outcomes of primary refractory disease in the modern treatment era have not yet been studied. We reviewed patients with MM treated with triplet/quadruplet therapy at our institution to assess the incidence of primary refractory disease and the impact of salvage therapies in this population. We identified 1127 patients, of whom 1086 were evaluated for hematologic responses after 4 to 6 cycles. Of these, 93.3% (1013) had evidence of response, whereas 6.7% (73) had primary refractory disease. With a median overall survival (OS) of 51.3 months, patients with primary refractory disease had an increased risk of shorter survival in univariable and multivariable analyses (hazard ratio [HR], 3.5 [95% confidence interval (CI), 2.5-4.9]; HR, 4.3 [95% CI, 2.6-6.9], respectively). In the subgroup analysis of patients with primary refractory disease, those who received second-line autologous stem cell transplantation (ASCT) had increased second progression-free survival (20.9 vs 8.1 months; P < .01) and second OS (74.7 vs 31.3 months; P = .02) compared with patients who did not. We conclude that early progression remains a significant factor for shorter OS in the current era, and salvage ASCT could be the most beneficial option for this population.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Neoplasias de Células Plasmáticas , Humanos , Quimioterapia de Inducción , Mieloma Múltiple/terapia , Trasplante AutólogoRESUMEN
Allogeneic stem cell transplant (allo SCT) for multiple myeloma (MM) is potentially curative in some, while toxic in many others. We retrospectively analyzed 85 patients diagnosed with MM who underwent allo SCT as frontline or salvage therapy between 2000 and 2022 at Mayo Clinic Rochester and examined patient outcomes and prognostic markers. Overall survival (OS), progression free survival (PFS), treatment related mortality (TRM), and relapse rates (RR) were estimated using the Kaplan Meier method and competing risk models. Median follow-up was 11.5 years. Median OS and PFS were 1.7 and 0.71 years, respectively. Five-year OS and PFS were 22.2% and 15.1%, respectively. One-year TRM was 23.5%. Twelve patients demonstrated durable overall survival, living 10+ years beyond their allo SCT. This subgroup was more likely to have no or one prior auto SCT (p = 0.03) and to have been transplanted between 2000 and 2010 (p = 0.03). Outcomes were poor in this cohort with long follow-up, with few patients surviving 5 years or more, and most relapsing or dying within 2 years. We would expect better outcomes and tolerability with an expanded array of novel therapeutics and would prefer them to allo SCT.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Estudios Retrospectivos , Supervivencia sin Progresión , Trasplante de Células MadreRESUMEN
Most patients with solitary bone plasmacytomas (SBP) progress to multiple myeloma (MM) after definitive radiation therapy as their primary treatment. Whether the presence of high-risk (HR) cytogenetic abnormalities by fluorescence in situ hybridization (FISH) in the clonal plasma cells, obtained either directly from the diagnostic SBP tissue or the corresponding bone marrow examination at the time of diagnosis, is associated with a shorter time to progression (TTP) to MM is unknown. This study evaluated all patients diagnosed with SBP at the Mayo Clinic from January 2012 to July 2022. The presence of del(17p), t(14;16), t(4;14), or +1q (gain or amplification) by FISH in clonal plasma cells was defined as HR. A total of 114 patients were included in this cohort, and baseline FISH was available for 55 patients (48%), of which 22 were classified as HR (40%). The median TTP to MM for patients with SBP and HR FISH was 8 months (95% confidence interval [CI], 6.3-26) compared with 42 months (95% CI, 25-not reached [NR]) in patients with SBP without HR FISH (P < .001). In a multivariate analysis, only HR FISH was a significant predictor for shorter TTP to MM, independent of minimal marrow involvement and an abnormal serum free light chain ratio at diagnosis. Deletion (17p) and gain 1q abnormalities were the most common FISH abnormalities responsible for the short TTP to MM. Thus, assessing for HR FISH abnormalities in clonal plasma cells derived from either the diagnostic SBP tissue or the staging bone marrow examination of patients with newly diagnosed SBP is feasible and prognostic for a shorter TTP to MM.
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Mieloma Múltiple , Plasmacitoma , Humanos , Plasmacitoma/genética , Hibridación Fluorescente in Situ , Aberraciones Cromosómicas , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Pronóstico , Progresión de la EnfermedadRESUMEN
Photon counting detector (PCD) computed tomography (CT) is a paradigm-shifting innovation in CT imaging which was recently granted approval for clinical use by the US Food and Drug Administration. PCD-CT allows the generation of multi-energy images with increased contrast and scanning speed or ultra-high spatial resolution (UHR) images with lower radiation doses, compared to the currently used energy integrating detector (EID) CT. Since the recognition of bone disease related to multiple myeloma is important for the diagnosis and management of patients, the advent of PCD-CT heralds a new era in superior diagnostic evaluation of myeloma bone disease. In a first-in-human pilot study, patients with multiple myeloma were imaged with UHR-PCD-CT to validate and establish the utility of this technology in routine imaging and clinical care. We describe 2 cases from that cohort to highlight the superior imaging performance and diagnostic potential of PCD-CT for multiple myeloma compared to clinical standard EID-CT. We also discuss how the advanced imaging capabilities from PCD-CT enhances clinical diagnostics to improve care and overall outcomes for patients.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico por imagen , Proyectos Piloto , Fantasmas de Imagen , Fotones , Tomografía Computarizada por Rayos X/métodosRESUMEN
In this phase 1/2 study, carfilzomib was added to high-dose melphalan conditioning prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma that had been treated with ≤2 prior lines of therapy. Carfilzomib was escalated at doses of 27, 36, 45, and 56 mg/m2 on days -6, -5, -2, and -1 before ASCT in the phase 1 component of the study. In addition, all the patients received melphalan 100 mg/m2 on days -4 and -3. The primary endpoint of the phase 1 component was to identify the maximum tolerated dose, and the primary endpoint of the phase 2 component was the rates of complete response (≥CR) at 1 year after ASCT. The phase 1 dose escalation cohort included 14 patients, and 35 patients were included in the phase 2 cohort. The maximum tested dose was 56 mg/m2 (MTD). The median time from diagnosis to study enrollment was 5.8 (range 3.4-88.4) months, and 16% of patients had obtained a ≥CR prior to ASCT. The best response within 1 year after ASCT was a ≥ CR rate in 22% for the entire cohort, and 22% for patients treated at the MTD. The ≥VGPR rates improved from 41% before ASCT to 77% by 1 year after ASCT. One patient had a grade 3 renal adverse event, and renal function returned to baseline with supportive care. The rate of grade 3-4 cardiovascular toxicity was 16%. The addition of carfilzomib to melphalan conditioning was safe and resulted in deep responses after ASCT.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Melfalán , Mieloma Múltiple/tratamiento farmacológico , Trasplante Autólogo , Acondicionamiento Pretrasplante/métodos , Trasplante de Células MadreRESUMEN
Multiple myeloma (MM) remains an incurable plasma cell (PC) malignancy. Although it is known that MM tumor cells display extensive intratumoral genetic heterogeneity, an integrated map of the tumor proteomic landscape has not been comprehensively evaluated. We evaluated 49 primary tumor samples from newly diagnosed or relapsed/refractory MM patients by mass cytometry (CyTOF) using 34 antibody targets to characterize the integrated landscape of single-cell cell surface and intracellular signaling proteins. We identified 13 phenotypic meta-clusters across all samples. The abundance of each phenotypic meta-cluster was compared to patient age, sex, treatment response, tumor genetic abnormalities and overall survival. Relative abundance of several of these phenotypic meta-clusters were associated with disease subtypes and clinical behavior. Increased abundance of phenotypic meta-cluster 1, characterized by elevated CD45 and reduced BCL-2 expression, was significantly associated with a favorable treatment response and improved overall survival independent of tumor genetic abnormalities or patient demographic variables. We validated this association using an unrelated gene expression dataset. This study represents the first, large-scale, single-cell protein atlas of primary MM tumors and demonstrates that subclonal protein profiling may be an important determinant of clinical behavior and outcome.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , Proteómica , Células Plasmáticas/metabolismoRESUMEN
Background Photon-counting detector (PCD) CT and deep learning noise reduction may improve spatial resolution at lower radiation doses compared with energy-integrating detector (EID) CT. Purpose To demonstrate the diagnostic impact of improved spatial resolution in whole-body low-dose CT scans for viewing multiple myeloma by using PCD CT with deep learning denoising compared with conventional EID CT. Materials and Methods Between April and July 2021, adult participants who underwent a whole-body EID CT scan were prospectively enrolled and scanned with a PCD CT system in ultra-high-resolution mode at matched radiation dose (8 mSv for an average adult) at an academic medical center. EID CT and PCD CT images were reconstructed with Br44 and Br64 kernels at 2-mm section thickness. PCD CT images were also reconstructed with Br44 and Br76 kernels at 0.6-mm section thickness. The thinner PCD CT images were denoised by using a convolutional neural network. Image quality was objectively quantified in two phantoms and a randomly selected subset of participants (10 participants; median age, 63.5 years; five men). Two radiologists scored PCD CT images relative to EID CT by using a five-point Likert scale to detect findings reflecting multiple myeloma. The scoring for the matched reconstruction series was blinded to scanner type. Reader-averaged scores were tested with the null hypothesis of equivalent visualization between EID and PCD. Results Twenty-seven participants (median age, 68 years; IQR, 61-72 years; 16 men) were included. The blinded assessment of 2-mm images demonstrated improvement in viewing lytic lesions, intramedullary lesions, fatty metamorphosis, and pathologic fractures for PCD CT versus EID CT (P < .05 for all comparisons). The 0.6-mm PCD CT images with convolutional neural network denoising also demonstrated improvement in viewing all four pathologic abnormalities and detected one or more lytic lesions in 21 of 27 participants compared with the 2-mm EID CT images (P < .001). Conclusion Ultra-high-resolution photon-counting detector CT improved the visibility of multiple myeloma lesions relative to energy-integrating detector CT. © RSNA, 2022 Online supplemental material is available for this article.
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Aprendizaje Profundo , Mieloma Múltiple , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Fantasmas de Imagen , Fotones , Tomografía Computarizada por Rayos X/métodos , FemeninoRESUMEN
High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Achievement of complete response (CR) and minimal residual disease (MRD) negativity are associated with improved progression-free survival (PFS) and overall survival (OS). With superior triplet- and quadruplet-based induction regimens, a higher proportion of patients are achieving deep responses of at least a very good partial response (VGPR) or better. The probability of achieving different levels of deeper hematologic responses post-ASCT based on the pre-ASCT depth of response is less clear in the existing literature but would be of value to patients and providers in discussing the added benefit of ASCT. We assessed the rate of deepening the hematologic response with upfront ASCT in patients with NDMM, mainly to MRD-negative CR, based on the response achieved after induction therapy. We retrospectively reviewed 210 patients with NDMM who underwent upfront ASCT at Mayo Clinic Rochester between May 1, 2018, and July 31, 2019. In addition to the availability of next-generation flow cytometry (NGF) testing for MRD status, which yielded a sensitivity of 10-5, the more sensitive mass spectrometry-based assessment of peripheral blood (ie, MASS-FIX) for monoclonal proteins was used rather than conventional immunofixation. Pre-ASCT, 23 patients (11%) achieved MRD-negative CR, which increased to 66 patients (31%) post-ASCT. Of 187 patients not in MRD-negative CR pre-ASCT, 45 (24%) converted to MRD-negative CR. Patients with MRD-positive CR before ASCT had the highest rates of conversion to MRD-negative CR. HR cytogenetics did not impact rates of MRD-negative CR achievement post-ASCT irrespective of pre-ASCT IMWG response (P = 1.0). Overall, irrespective of IMWG response, 43 patients (20%) were MRD-negative pre-ASCT (19 in VGPR, 24 in CR or sCR), and 102 patients (49%) were MRD-negative post-ASCT (36 in VGPR, 66 in CR or sCR). Among 85 patients with VGPR post-ASCT, 36 achieved MRD negativity, of whom 8 (22%) progressed, whereas 49 had MRD-positive disease, of whom 24 (49%) progressed (P = .014). Upfront ASCT in patients with NDMM led to deeper responses, with 24% converting to MRD negative CR and more than doubling of the total rate of MRD negativity irrespective of IMWG response depth.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Trasplante Autólogo , Mieloma Múltiple/terapia , Estudios Retrospectivos , Quimioterapia de Inducción , Resultado del TratamientoRESUMEN
BACKGROUND: Dual-energy CT with virtual noncalcium (VNCa) images allows the evaluation of focal intramedullary bone marrow involvement in patients with multiple myeloma. However, current commercial VNCa techniques suffer from excessive image noise and artifacts due to material decomposition used in synthesizing VNCa images. OBJECTIVES: In this work, we aim to improve VNCa image quality for the assessment of focal multiple myeloma, using an Artificial intelligence based Generalizable Algorithm for mulTi-Energy CT (AGATE) method. MATERIALS AND METHODS: AGATE method used a custom dual-task convolutional neural network (CNN) that concurrently carries out material classification and quantification. The material classification task provided an auxiliary regularization to the material quantification task. CNN parameters were optimized using custom loss functions that involved cross-entropy, physics-informed constraints, structural redundancy in spectral and material images, and texture information in spectral images. For training data, CT phantoms (diameters 30 to 45 cm) with tissue-mimicking inserts were scanned on a third generation dual-source CT system. Scans were performed at routine dose and half of the routine dose. Small image patches (i.e., 40 × 40 pixels) of tissue-mimicking inserts with known basis material densities were extracted for training samples. Numerically simulated insert materials with various shapes increased diversity of training samples. Generalizability of AGATE was evaluated using CT images from phantoms and patients. In phantoms, material decomposition accuracy was estimated using mean-absolute-percent-error (MAPE), using physical inserts that were not used during the training. Noise power spectrum (NPS) and modulation transfer function (MTF) were compared across phantom sizes and radiation dose levels. Five patients with multiple myeloma underwent dual-energy CT, with VNCa images generated using a commercial method and AGATE. Two fellowship-trained musculoskeletal radiologists reviewed the VNCa images (commercial and AGATE) side-by-side using a dual-monitor display, blinded to VNCa type, rating the image quality for focal multiple myeloma lesion visualization using a 5-level Likert comparison scale (-2 = worse visualization and diagnostic confidence, -1 = worse visualization but equivalent diagnostic confidence, 0 = equivalent visualization and diagnostic confidence, 1 = improved visualization but equivalent diagnostic confidence, 2 = improved visualization and diagnostic confidence). A post hoc assignment of comparison ratings was performed to rank AGATE images in comparison to commercial ones. RESULTS: AGATE demonstrated consistent material quantification accuracy across phantom sizes and radiation dose levels, with MAPE ranging from 0.7% to 4.4% across all testing materials. Compared to commercial VNCa images, the AGATE-synthesized VNCa images yielded considerably lower image noise (50-77% noise reduction) without compromising noise texture or spatial resolution across different phantom sizes and two radiation doses. AGATE VNCa images had markedly reduced area under NPS curves and maintained NPS peak frequency (0.7 lp/cm to 1.0 lp/cm), with similar MTF curves (50% MTF at 3.0 lp/cm). In patients, AGATE demonstrated reduced image noise and artifacts with improved delineation of focal multiple myeloma lesions (all readers comparison scores indicating improved overall diagnostic image quality [scores 1 or 2]). CONCLUSIONS: AGATE demonstrated reduced noise and artifacts in VNCa images and ability to improve visualization of bone marrow lesions for assessing multiple myeloma.
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Aprendizaje Profundo , Mieloma Múltiple , Inteligencia Artificial , Humanos , Mieloma Múltiple/diagnóstico por imagen , Fantasmas de Imagen , Dosis de Radiación , Tomografía Computarizada por Rayos X/métodosRESUMEN
Background: Clinicians have limited time during patient encounters which can result in patients' concerns not being addressed. This study's objective was to test whether an electronic patient-reported outcome quality of life tool (PROQOL) in which patients identify their primary concern during clinic visits improves cancer patient quality of life (QOL). Patients and methods: This single center non-blinded prospective clinical trial randomized patients (2:1) to PROQOL versus usual care (UC). Two patient cohorts were enrolled: those with hematologic malignancies (multiple myeloma [MM] or light chain amyloidosis [AL]) and solid tumors (head and neck [H/N] or gynecologic [GYN] malignancies). Primary endpoint was patient-reported QOL at 12 months measured by a single-item Linear Analog Self-Assessment. Value to patients and impact on clinician workflow was measured using a "was it worth it" survey. The study was powered to detect a 0.5 standard deviation difference between groups. Results: Overall 383 patients were enrolled, 171 with MM, 62 AL, 113 GYN, and 37 H/N between July 2016 and April 2018, with 12-month follow-up. There were 171 (44.6%) male patients and median age was 62 years (range 31-87). The most often selected concern was physical health (30.9%), and second was cancer diagnosis and treatment (29.1%). Mean QOL was 7.12 for PROQOL and 6.98 for UC (0-10 scale) at 12 months, with no between-group difference overall (p = 0.56) or within hematologic or solid tumor cohorts, respectively. Among patients, 74% thought the PROQOL tool was worthwhile, 86% would choose PROQOL again, and 81% would recommend it to others. Among clinicians, 95% responded that PROQOL was worthwhile and did not think that PROQOL negatively impacted their workflow. Conclusions: Although we did not demonstrate a QOL difference between PROQOL and UC groups; the PROQOL tool held considerable value in identifying patients' main concerns over time and was worthwhile for patients and clinicians.
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Clinical success with intravenous (IV) oncolytic virotherapy (OV) has to-date been anecdotal. We conducted a phase 1 clinical trial of systemic OV and investigated the mechanisms of action in responding patients. A single IV dose of vesicular stomatitis virus (VSV) interferon-ß (IFN-ß) with sodium iodide symporter (NIS) was administered to patients with relapsed/refractory hematologic malignancies to determine safety and efficacy across 4 dose levels (DLs). Correlative studies were undertaken to evaluate viremia, virus shedding, virus replication, and immune responses. Fifteen patients received VSV-IFNß-NIS. Three patients were treated at DL1 through DL3 (0.05, 0.17, and 0.5 × 1011 TCID50), and 6 were treated at DL4 (1.7 × 1011 TCID50) with no dose-limiting toxicities. Three of 7 patients with T-cell lymphoma (TCL) had responses: a 3-month partial response (PR) at DL2, a 6-month PR, and a complete response (CR) ongoing at 20 months at DL4. Viremia peaked at the end of infusion, g was detected. Plasma IFN-ß, a biomarker of VSV-IFNß-NIS replication, peaked between 4 hours and 48 hours after infusion. The patient with CR had robust viral replication with increased plasma cell-free DNA, high peak IFN-ß of 18 213 pg/mL, a strong anti-VSV neutralizing antibody response, and increased numbers of tumor reactive T-cells. VSV-IFNß-NIS as a single agent was effective in patients with TCL, resulting in durable disease remissions in heavily pretreated patients. Correlative analyses suggest that responses may be due to a combination of direct oncolytic tumor destruction and immune-mediated tumor control. This trial is registered at www.clinicaltrials.gov as #NCT03017820.