Decision-making factors for an autologous stem cell transplant for older adults with newly diagnosed multiple myeloma: A qualitative analysis

PurposeA 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.MethodsA qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in <12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis.ResultsEighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with their treatment decision with “trust in their oncologist” and “wanting the best treatment” as the most important to proceed with ASCT. “Afraid of side effects” was the most common reason for declining ASCT. Fifteen oncologists completed the survey and 10 follow-up interviews were conducted. Most relied on the ‘eye-ball’ test for ASCT eligibility over geriatric screening tools. The lack of both high-quality evidence and local guidelines impacted decision-making. Both oncologists and patients felt that chronological age alone should not affect ASCT eligibility.ConclusionWhile decision-making factors regarding ASCT can be variable, both oncologists and patients indicated that chronological age alone should not represent a barrier for ASCT among older adults. Future simplification and incorporation of ASCT eligibility geriatric assessment tools in studies as well as the inclusion of these tools in local guidelines may further improve ASCT decision-making

D-dimer predicts venous thromboembolism in multiple myeloma: A nested case-control study

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-dimer with VTE in MM. METHODS: We identified 545 patients with newly diagnosed MM. Using a nested case-control design, we identified 38 cases of VTE within 6-months of MM treatment and 137 randomly selected controls. Using logistic regression, we examined the association between D-dimer and sP-selectin with VTE. We also analyzed the association after adjusting for IMPEDE VTE. RESULTS: Each 1-point increase in IMPEDE VTE score was associated with a 27% increase in odds of VTE (odds ratio 1.27; 95% CI 1.08-1.51; CONCLUSION: Among patients with newly diagnosed MM starting chemotherapy, D-dimer was associated with increased odds of developing VTE within the subsequent 6-months. The addition of D-dimer to IMPEDE VTE

Machine learning-based scoring models to predict hematopoietic stem cell mobilization in allogeneic donors

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 administration, and a small percentage of the donors fail to mobilize an optimal number of stem cells necessary for a safe allogeneic stem cell transplant. In this study, we retrospectively reviewed 1361 related allogeneic donors who underwent stem cell mobilization at Washington University. We compared the standard mobilization agent G-CSF with five alternative mobilization regimens, including GM-CSF, G-CSF+GM-CSF, GM-CSF + Plerixafor, Plerixafor and BL-8040. Cytokine-based mobilization strategies (G-CSF or in combination with GM-CSF) induce higher CD34 cell yield after 4-5 consecutive days of treatment, while CXCR4 antagonists (plerixafor and BL-8040) induce significantly less but rapid mobilization on the same day. Next, using a large dataset containing the demographic and baseline laboratory data from G-CSF-mobilized donors, we established machine learning (ML)-based scoring models that can be used to predict patients who may have less than optimal stem cell yields after a single leukapheresis session. To our knowledge, this is the first prediction model at the early donor screening stage, which may help identify allogeneic stem cell donors who may benefit from alternative approaches to enhance stem cell yields, thus ensuring safe and effective stem cell transplantation

Comprehensive characterization of the multiple myeloma immune microenvironment using integrated scRNA-seq, CyTOF, and CITE-seq analysis

UNLABELLED: 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 concordance of measurements among single-cell techniques. Cell type abundances are relatively consistent across the three approaches, while variations are observed in T cells, macrophages, and monocytes. Concordance and correlation analysis of cell type marker gene expression across different modalities highlighted the importance of choosing cell type marker genes best suited to particular modalities. By integrating data from these three assays, we found International Staging System stage 3 patients exhibited decreased CD4 SIGNIFICANCE: scRNA-seq, CyTOF, and CITE-seq are increasingly used for evaluating cellular heterogeneity. Understanding their concordances is of great interest. To date, this study is the most comprehensive examination of the measurement of the immune microenvironment in multiple myeloma using the three techniques. Moreover, we identified markers predicted to be significantly associated with multiple myeloma rapid progression

Impact of the COVID-19 pandemic on breast, colorectal, lung, and prostate cancer stage at diagnosis according to race

PURPOSE: To determine if the COVID-19 pandemic has further exacerbated racial disparities in late-stage presentation of breast, colorectal, lung, and prostate cancers. METHODS: We conducted a registry-based retrospective study of patients with newly reported diagnoses of breast, colorectal, lung, and prostate cancers between March 2019-June 2019 (pre-COVID-19) and March 2020-June 2020 (early-COVID-19). We compared the volume of new diagnoses and stage at presentation according to race between both periods. RESULTS: During the study period, a total of 3528 patients had newly diagnosed cancer; 3304 of which had known disease stages and were included in the formal analyses. 467 (14.1%) were Blacks, and 2743 were (83%) Whites. 1216 (36.8%) had breast, 415 (12.6%) had colorectal, 827 (25%) had lung, and 846 (25.6%) had prostate cancers, respectively. The pre-COVID-19 period included 2120 (64.2%), and the early-COVID-19 period included 1184 (35.8%), representing a proportional 44.2% decline in the volume of new cases of breast, colorectal, lung, and prostate cancers, p \u3c 0.0001. Pre-COVID-19, 16.8% were diagnosed with metastatic disease, versus 20.4% early-COVID-19, representing a proportional increase of 21.4% in the numbers of new cases with metastatic disease, p = 0.01. There was a non-significant proportional decline of 1.9% in Black patients diagnosed with non-metastatic breast, colorectal, lung, and prostate cancers early-COVID-19 (p = 0.71) and a non-significant proportional increase of 7% in Black patients diagnosed with metastatic disease (p = 0.71). Difference-in-difference analyses showed no statistically significant differences in metastatic presentation comparing Black to White patients. CONCLUSION: While we identified substantial reductions in the volume of new cancer diagnoses and increases in metastatic presentations due to the COVID-19 pandemic, the impact was similar for White and Black patients

Preferences and priorities for relapsed multiple myeloma treatments among patients and caregivers in the United States

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. The DCE included six attributes with varying levels including progression-free survival (PFS), toxicity, and mode and frequency of administration. In addition, the impact of treatment cost was assessed using a fixed-choice question. The BWS exercise included 18 items (modes and frequency of administration, additional treatment convenience, and toxicity items). The survey was administered online to patients recruited from the Multiple Myeloma Research Foundation CoMMpass study (NCT01454297). Results: The final samples consisted of 94 patients and 32 caregivers. Avoiding severe nerve damage was most important to patients, followed by longer PFS. Caregivers considered PFS to be the most important attribute. We estimate that a third or more of patients were cost-sensitive, meaning their treatment preference was altered based on cost implications. Caregivers were not cost-sensitive. The three most bothersome treatment features in the BWS exercise were risk of kidney failure, lowering white blood cell counts, and weakening the immune system. Conclusion: Patients with relapsed or refractory MM and their caregivers consider many factors including efficacy, toxicity, mode/frequency of administration, and cost in their decisions regarding treatment options. The study provides a basis for future Research on patient and caregiver treatment preferences, which could be incorporated into shared decision-making with physicians

Distinct clonal identities of B-ALLs arising after lenolidomide therapy for multiple myeloma

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. Patient samples were evaluated through sequencing, cytogenetics/fluorescence in situ hybridization (FISH), immunohistochemical (IHC) staining, and immunoglobulin heavy chain (IgH) clonality assessment. Samples were assessed for shared mutations and recurrently mutated genes. Through whole exome sequencing and cytogenetics/FISH analysis of 7 paired samples (MM vs matched B-ALL), no mutational overlap between samples was observed. Unique dominant IgH clonotypes between the tumors were observed in 5 paired MM/B-ALL samples. Across all 17 B-ALL samples, 14 (83%) had a TP53 variant detected. Three MM samples with sufficient sequencing depth (\u3e500×) revealed rare cells (average of 0.6% variant allele frequency, or 1.2% of cells) with the same TP53 variant identified in the subsequent B-ALL sample. A lack of mutational overlap between MM and B-ALL samples shows that B-ALL developed as a second malignancy arising from a founding population of cells that likely represented unrelated clonal hematopoiesis caused by a TP53 mutation. The recurrent variants in TP53 in the B-ALL samples suggest a common path for malignant transformation that may be similar to that of TP53-mutant, treatment-related acute myeloid leukemia. The presence of rare cells containing TP53 variants in bone marrow at the initiation of lenalidomide treatment suggests that cellular populations containing TP53 variants expand in the presence of lenalidomide to increase the likelihood of B-ALL development