Nonbiological factors affecting outcomes in adolescents and young adults with lymphoma.

The impact of nonbiological factors (NBF) on survival was investigated in a large cohort of adolescents and young adults (AYA) with lymphoma in the United States (US). We found that uninsured and Medicaid AYA beneficiaries with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) are at significantly increased risk of death when compared with their insured counterpart even after adjustment for other factors affecting survival. Increased risk of death was also noted for Non-Hispanic Black (NHB) patients with cHL and NHL when compared to Non-Hispanic White (NHW) patients, however, only Hispanic patients with NHL were found to have a significantly increased mortality risk while those with cHL were not. NHL AYA patients residing in lower-income counties are at increased risk of death. The strong association of NBF with survival indicates opportunities to improve the survival of AYA lymphoma patients by improving access/quality of care in the US.

Global disparities in patients with multiple myeloma: a rapid evidence assessment.

There are disparities in outcomes for patients with multiple myeloma (MM). We evaluated the influence of sociodemographic factors on global disparities in outcomes for patients with MM. This rapid evidence assessment (PROSPERO, CRD42021248461) followed PRISMA-P guidelines and used the PICOS framework. PubMed and Embase® were searched for articles in English from 2011 to 2021. The title, abstract, and full text of articles were screened according to inclusion/exclusion criteria. The sociodemographic factors assessed were age, sex, race/ethnicity, socioeconomic status, and geographic location. Outcomes were diagnosis, access to treatment, and patient outcomes. Of 84 articles included, 48 were US-based. Worldwide, increasing age and low socioeconomic status were associated with worse patient outcomes. In the US, men typically had worse outcomes than women, although women had poorer access to treatment, as did Black, Asian, and Hispanic patients. No consistent disparities due to sex were seen outside the US, and for most factors and outcomes, no consistent disparities could be identified globally. Too few studies examined disparities in diagnosis to draw firm conclusions. This first systematic analysis of health disparities in patients with MM identified specific populations affected, highlighting a need for additional research focused on assessing patterns, trends, and underlying drivers of disparities in MM.

Clinical implications of measurable residual disease assessment in multiple myeloma in the era of quadruplet therapy.

Multiple myeloma is a complex hematological malignancy with substantial heterogeneity in its clinical manifestations, biological processes, and patient outcomes. Although many biomarkers with have been identified to assist with disease monitoring and prognostication, predictive markers that inform treatment decisions remain elusive. As treatments become more effective, assays for measurable residual disease (MRD) below the level of detection of traditional assays have emerged as an essential component of disease assessment with powerful prognostic value for dynamic risk assessment. As its role as a potentially predictive biomarker continues to evolve, it is increasingly clear that MRD assessment has substantial clinical utility in the evaluation of patients with myeloma. In this review, we will summarize the evidence supporting the role of MRD as a prognostic biomarker and highlight the current clinical implications and future applications of MRD assessment in multiple myeloma.

Impact of autologous hematopoietic cell transplantation on disease burden quantified by next-generation sequencing in multiple myeloma treated with quadruplet therapy.

The incremental impact of autologous hematopoietic cell transplantation (AHCT) on disease burden with quadruplet induction in newly diagnosed multiple myeloma (NDDM) can be reappraised with the serial assessment of minimal residual disease (MRD). We describe the impact of AHCT on MM burden assessed by next-generation sequencing (NGS) for patients enrolled in a clinical trial utilizing quadruplet induction, AHCT, followed by MRD-adapted consolidation. We describe quantitative changes in MRD burden with AHCT and explore patient and disease features influencing the magnitude of MRD reduction with AHCT. Among 123 included patients, 109 underwent AHCT and had MRD assessment pre and post AHCT. Forty percent achieved MRD < 10-5 post-induction, increasing to 70% after AHCT. Of the 65 patients (60%) who remained MRD positive post-induction, 54 (83%) had a reduction in MRD burden with AHCT. The median reduction in MRD with AHCT was 1.10 log10 (range, -1.26 to 3.41). Patients with high-risk cytogenetic abnormalities (HRCA) had greater reduction in MRD burden (p = .02) after AHCT. Median relative reduction was 0.91 log10 (range, -0.75 to 2.14), 1.26 log10 (range, -0.21 to 3.26) and 1.34 log10 (range, -1.28 to 3.41) for patients with 0, 1 and 2+ HRCA, respectively. The presence of HRCA was the only factor associated with greater than 1 log10 reduction in MRD burden with AHCT. Serial NGS MRD demonstrates the incremental effect of AHCT in MM marrow burden in the context of quadruplet induction, particularly in high-risk MM.

Impact of insurance status on the survival of younger patients diagnosed with acute promyelocytic leukemia in the United States.

BACKGROUND: Survival among patients diagnosed with acute promyelocytic leukemia (APL) has significantly improved with the use of all-trans retinoic acid and arsenic trioxide. However, the need for immediate diagnosis and access to specialized care and the cost associated with APL management can potentially act as barriers for disadvantaged patients. The influence of sociodemographic factors on the outcomes of patients with APL remains unclear. METHODS: The authors used the National Cancer Institute's Surveillance, Epidemiology, and End Results program to characterize the impact of sociodemographic factors on survival in patients younger than 65 years with APL. RESULTS: The authors identified 1787 cases: 816 who were younger than 40 years and 971 who were 40 years old or older. Insured patients who were younger than 40 years had an improved 5-year overall survival (OS) rate in comparison with patients without insurance. Among patients who were 40 years or older, having insurance (other than Medicaid) was associated with better survival than being a Medicaid beneficiary or being uninsured, whereas patients with Medicaid had improved 5-year OS in comparison with uninsured patients. In a multivariate analysis of patients younger than 40 years, a higher risk of death was associated with being male, being diagnosed in earlier years, and being uninsured. For patients who were 40 years old or older, mortality increased with increasing age and for both Medicaid and uninsured patients in comparison with insured patients. CONCLUSIONS: Despite the high cure rate experienced by patients with APL, patients younger than 65 years without insurance and those 40 years old or older with Medicaid are at a significant disadvantage in comparison with patients with insurance. These findings point to an opportunity to improve survival in APL by addressing access to care.

International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials.

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

Second primary malignancy among older adults with multiple myeloma receiving first-line lenalidomide-based therapy: A population-based analysis.

OBJECTIVES: Clinical trials have suggested that patients with myeloma treated with lenalidomide may have an increased risk of second primary malignancies (SPM). Whether such risks are of significant relevance in the real-world clinical practice, particularly among older patients receiving first-line lenalidomide based therapy, remains unclear. METHODS: Using Surveillance Epidemiology and End Results-Medicare database, we identified adults ≥ 65 years with plasma cell myeloma diagnosed in 2007-2015 who received at least one oral anti-myeloma agent. We defined first-line lenalidomide-containing therapy as use within 90 days of diagnosis. SPM was defined as a malignancy reported to a cancer registry > 90 days after myeloma diagnosis. We computed cumulative incidence of SPM (with death being a competing event) and compared SPM rates between patients treated with or without first-line lenalidomide using a Fine-Gray's model, adjusting for age, sex, race, ethnicity, prior malignancy, and histologic subtype. RESULTS: Of 9850 Medicare beneficiaries, 4009 (41%) received first-line lenalidomide. During median follow up of 5.0 years, 423 patients (4.3%) developed SPM, including 361 solid tumors (85%) and 61 hematologic malignancies (14%). The cumulative incidence of any SPM at 5 years was similar among those who received first-line lenalidomide and those who did not (5.3% vs 4.4%; sub-hazard ratio, SHR 1.06, P = .53). Consistent results were seen in the risk of solid tumor (4.7% vs 3.6%; SHR 1.13, P = .24) or hematologic malignancy (4.7 vs 3.6%, SHR 0.73; P = .72). CONCLUSION: First-line lenalidomide therapy among older adults with myeloma was not associated with a significantly increased risk of any SPM.

Best practices for the assessment of measurable residual disease (MRD) in multiple myeloma.

Therapeutic advances in multiple myeloma have led to durable, deep remissions in a subset of patients. However, outcomes of patients achieving a complete response are not homogeneous. In recent years, measurable residual disease (MRD) has emerged as a prognostic biomarker. While several technologies have been evaluated to detect MRD, two assessment technologies are most frequently utilized in patients with multiple myeloma. Next-generation flow (NGF) uses flow cytometry to identify malignant plasma cells through the presence of immunologic markers located on the cell surface. Next-generation sequencing (NGS) analyzes for the presence of sequences in immunoglobulin genes that were previously identified as markers of that specific patient's plasma cell malignant clone. Both methods are included in criteria for MRD by the International Myeloma Working Group, which defines MRD negativity as less than 10-5. Recently, the NGS-based clonoSEQ® Assay obtained clearance from the US Food and Drug Administration, with a limit of detection of less than 10-6 given proper sample input. Based on available evidence correlating attainment of MRD negativity with outcomes, MRD assessment has been incorporated into ongoing clinical trials. Analyses will provide additional insight into the correlation between MRD and outcome. This monograph examines the available trial data and provides recommendations on how to incorporate MRD assessment into clinical management.

Challenges and opportunities in the assessment of measurable residual disease in multiple myeloma.

Treatment response assessment in multiple myeloma (MM) relies on the detection of paraprotein in serum and/or urine, bone marrow morphology and immunohistochemistry. With remarkable advances in therapy, particularly in the newly diagnosed setting, achievement of complete remission became frequent, creating the need to identify smaller amounts of residual disease and understand their prognostic and therapeutic implications. Measurable residual disease (MRD) can be assessed primarily by flow cytometry and next generation sequencing and state-of-the-art assays have sensitivity approaching 1 in 106 cells. This review discusses the existing challenges in utilizing MRD to inform management of MM and highlights open research questions and opportunities as MRD is more routinely incorporated into clinical practice for patients with MM.

Mobilization of Hematopoietic Progenitor Cells for Autologous Transplantation Using Pegfilgrastim and Plerixafor: Efficacy and Cost Implications.

Filgrastim (FIL) is the most common growth factor combined with plerixafor for autologous hematopoietic progenitor cell mobilization, but requires daily, multi-injection administration. We adopted a standardized mobilization regimen with pegfilgrastim (PEG) and upfront plerixafor, allowing for a single injection given the long half-life and slow elimination of PEG. Between 2015 and 2017, a total of 235 patients with lymphoma or plasma cell dyscrasias underwent mobilization with PEG 6 mg on day 1 and upfront plerixafor 24 mg on day 3, followed by apheresis on day 4 regardless of peripheral blood CD34+ cells. The median CD34+ cells/mm3 in peripheral blood on first day of collection was 48 and median collection yield was 7.27 × 106 CD34+ cells/kg (range, 0.32 to 39.6 × 106 CD34+ cells/kg) after a mean of 1.6 apheresis collections. Overall, 83% of patients achieved the mobilization target, and 95% reached the minimum necessary CD34+ cell yield to proceed with transplantation (2 × 106 CD34+ cells/kg). Because FIL is weight-based and dosed daily, the cost comparison with PEG is influenced by patient weight and number of apheresis sessions required. A cost simulation using actual patient data indicates that PEG is associated with lower cost than FIL for the majority of patients. Autologous hematopoietic progenitor cell mobilization with PEG and plerixafor is practical, effective, and not associated with increased cost compared with FIL mobilization.

Choosing Wisely BMT: American Society for Blood and Marrow Transplantation and Canadian Blood and Marrow Transplant Group's List of 5 Tests and Treatments to Question in Blood and Marrow Transplantation.

Choosing Wisely encourages dialogue about reducing unnecessary procedures, tests, or treatments in healthcare. The American Society for Blood and Marrow Transplantation (ASBMT) and Canadian Blood and Marrow Transplant Group (CBMTG) established a Choosing Wisely BMT Task Force whose objective was to create a list of top 5 practices in blood and marrow transplantation to be questioned. The Task Force consisted of representatives from ASBMT's Quality Outcomes, Education, and Practice Guidelines committees; ASBMT's Pharmacy Special Interest Group; CBMTG Program Directors; and Center for International Blood and Marrow Transplant Research (CIBMTR). Suggestions for current transplantation practices to question were elicited from the CBMTG Program Directors; members of ASBMT's Quality Outcomes, Practice Guidelines, and Education committees; and chairs of the CIBMTR scientific working committees. We received 119 unique suggestions that were ranked based on their potential impact on harm reduction, cost reduction, necessity of the test or practice, and the strength of available evidence. Through a modified Delphi process, suggestions were narrowed down to 6, which were then subjected to systematic reviews. The final 5 recommendations focus on graft source for patients with aplastic anemia, corticosteroid dose for initial treatment of graft-versus-host-disease, optimal number of umbilical cord blood units for transplantation, graft source in matched unrelated donor transplantation, and use of prophylactic intravenous immunoglobulin in transplant recipients. These Choosing Wisely BMT recommendations are relevant to the current clinical practice of blood and marrow transplantation and focus on tests, treatments, or procedures that may be harmful, wasteful, or for which there is no apparent clinical benefit.

Impact of marital status, insurance status, income, and race/ethnicity on the survival of younger patients diagnosed with multiple myeloma in the United States.

BACKGROUND: Recent advances in the treatment of multiple myeloma (MM) have been associated with improved survival, predominantly among young and white patients. The authors hypothesized that sociodemographic factors, adjusted for race/ethnicity, influence the survival of younger patients with MM. METHODS: Overall survival (OS) data were obtained for individuals included in the Surveillance, Epidemiology, and End Results (SEER-18) program who were diagnosed with MM before the age of 65 years between 2007 and 2012. The sociodemographic variables addressed were marital status, insurance status, median household income, and educational achievement in the county of residence. Race/ethnicity was defined as a self-reported construct including Hispanic (regardless of race), non-Hispanic black, non-Hispanic white, and other. RESULTS: There were 10,161 cases of MM included with a median follow-up of 27 months (range, 0-71 months; 22,179 person-years). Using multivariable Cox proportional hazards analysis, SEER registry; age; male sex; and 3 sociodemographic factors including marital status (other than married), insurance status (uninsured or Medicaid), and county-level income (lowest 2 quartiles), but not race/ethnicity, were found to be associated with an increased risk of death. The 4-year estimated OS rate was 71.1%, 63.2%, 53.4%, and 46.5% (P<.001), respectively, for patients with 0, 1, 2, or 3 adverse sociodemographic factors. Hispanic and non-Hispanic black individuals were found to have more adverse sociodemographic factors and worse OS. However, when the population was stratified by the cumulative number of sociodemographic factors, no consistent association between race/ethnicity and OS was observed after adjustment for confounders. CONCLUSIONS: Sociodemographic factors that potentially affect care, but not race/ethnicity, were found to influence the survival of younger patients with MM. Cancer 2016;122:3183-90. © 2016 American Cancer Society.

Nonbiological factors affecting survival in younger patients with acute myeloid leukemia.

BACKGROUND: Progress has been made in determining the biological variants of acute myelogenous leukemia (AML) and their prognostic implications. However, to the authors' knowledge, little is known regarding the impact of nonbiological factors (NBFs) on the survival of patients with AML. METHODS: The impact of NBFs (marital status, insurance status, county-level income, and education) on survival was assessed along with biological factors (disease subtype, sex, age, and race/ethnicity) using a cohort of patients aged 19 to 64 years who were diagnosed with AML between 2007 and 2011 and reported to the Surveillance, Epidemiology, and End Results program registry (SEER 18). RESULTS: There were 5541 patients included. The median overall survival for the entire study population was 16 months. On multivariate analysis, an increased risk of death was independently linked to being a Medicaid beneficiary, uninsured, single, divorced, and residing in a county within the lower 3 quintiles of median household income. NBFs affected the risk of early (<2 months) and late mortality and their impact was confirmed among patients known to have received chemotherapy. CONCLUSIONS: Insurance status, marital status, and county-level income were found to independently affect the survival of younger patients with AML and should be integrated into outcome comparisons. Interventions are needed to mitigate the impact of social factors on survival among patients with AML.

National prevalence survey in Brazil to evaluate the quality of microbiology laboratories: the importance of defining priorities to allocate limited resources.

This report describes a survey of microbiology laboratories (n = 467) serving Brazilian hospitals with ≥10 intensive care beds and/or involved in the government health care adverse event reporting system. Coordinators were interviewed and laboratories classified as follows: Level 0 (no minimal functioning conditions-85.4% of laboratories); Level 1 (minimal functioning conditions but inadequate execution of basic routine-6.7%); Level 2 (minimal functioning conditions and adequate execution of basic routine but no adequate procedures for quality control-5.8%); Level 3 (minimal functioning conditions, adequate execution of basic routine, and adequate procedures for quality control, but no direct communication with the infection control department-0.9%); Level 4 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, and direct communication with infection control, but no available advanced resources-none); and Level 5 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, direct communication with infection control, and available advanced resources-0.9%). Twelve laboratories did not perform Ziehl-Neelsen staining; 271 did not have safety cabinets; and >30% without safety cabinets had automated systems. Low quality was associated with serving hospitals not participating in government adverse-event program; private hospitals; nonteaching hospitals; and those outside state capitals. Results may reflect what occurs in many other countries where defining priorities is important due to limited resources.

National prevalence survey in Brazil to evaluate the quality of microbiology laboratories: the importance of defining priorities to allocate limited resources / Encuesta de prevalencia nacional para evaluar la calidad de los laboratorios de microbiología en el Brasil: importancia de la definición de prioridades para asignar recursos limitados

This report describes a survey of microbiology laboratories (n = 467) serving Brazilian hospitals with >10 intensive care beds and/or involved in the government health care adverse event reporting system. Coordinators were interviewed and laboratories classified as follows: Level 0 (no minimal functioning conditions-85.4% of laboratories); Level 1 (minimal functioning conditions but inadequate execution of basic routine-6.7%); Level 2 (minimal functioning conditions and adequate execution of basic routine but no adequate procedures for quality control-5.8%); Level 3 (minimal functioning conditions, adequate execution of basic routine, and adequate procedures for quality control, but no direct communication with the infection control department-0.9%); Level 4 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, and direct communication with infection control, but no available advanced resources-none); and Level 5 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, direct communication with infection control, and available advanced resources-0.9%). Twelve laboratories did not perform Ziehl-Neelsen staining; 271 did not have safety cabinets; and >30% without safety cabinets had automated systems. Low quality was associated with serving hospitals not participating in government adverse-event program; private hospitals; nonteaching hospitals; and those outside state capitals. Results may reflect what occurs in many other countries where defining priorities is important due to limited resources.

Este artículo describe una encuesta realizada en Brasil en laboratorios de microbiología (n = 467) que prestaban servicio a hospitales que contaban al menos con 10 camas de cuidados intensivos. Se entrevistó a los coordinadores y los laboratorios se clasificaron de la siguiente manera: nivel 0 (sin condiciones de funcionamiento mínimas: 85,4% de los laboratorios), nivel 1 (condiciones de funcionamiento mínimas pero ejecución inadecuada del trabajo habitual básico: 6,7%), nivel 2 (condiciones de funcionamiento mínimas y ejecución adecuada del trabajo habitual básico, pero sin procedimientos de control de calidad apropiados: 5,8%), nivel 3 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico y procedimientos de control de calidad apropiados, pero sin comunicación directa con el departamento de control de infecciones: 0,9%), nivel 4 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico, procedimientos de control de calidad apropiados y comunicación directa con el departamento de control de infecciones, pero sin recursos avanzados disponibles: ningún laboratorio) y nivel 5 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico, procedimientos de control de calidad apropiados, comunicación directa con el departamento de control de infecciones y recursos avanzados disponibles: 0,9%). Doce laboratorios no realizaban la tinción de Ziehl-Neelsen, 271 no contaban con cámaras de seguridad biológica, y más de 30% de los laboratorios que carecían de cámaras de seguridad biológica tenían sistemas automatizados. La escasa calidad se asoció a la falta de participación en el programa gubernamental de notificación de acontecimientos adversos, a los hospitales privados, a los hospitales no docentes y a la ubicación de los hospitales fuera de las capitales de los estados. Los resultados pueden reflejar lo que ocurre en muchos otros países con recursos limitados, donde es importante definir las prioridades.