Life In Myeloma Patients Research Articles

Bone Pain in Multiple Myeloma (BPMM)-A Protocol for a Prospective, Longitudinal, Observational Study.

Simple SummaryMultiple myeloma is a bone marrow cancer that often causes bone pain, but little is known about the pain characteristics and mechanisms in this condition. This clinical study aims to: 1. characterize the type, location and intensity of pain in myeloma patients, and its effect of quality of life, and 2. investigate whether the nerve fibers in the bone of myeloma patients are altered. We will also explore whether pain intensity is correlated to blood indicators of inflammation or bone damage. Study results will help identify the mechanisms of myeloma-induced bone pain, allowing the development of new analgesics for these patients.Multiple myeloma (MM) is a bone marrow neoplasia that causes bone pain in 70% patients. While preclinical models of MM have suggested that both nerve sprouting and nerve injury may be causative for the pain, there is a lack of clinical data. Thus, the primary aims of this clinical study are: (1) to provide a deep characterization of the subjective experience of pain and quality of life in MM patients; (2) to investigate disturbances in the bone innervation of MM patients. Secondary aims include exploring correlations between pain and serum inflammatory and bone turnover biomarkers. In a prospective, observational study (clinicaltrials.gov: NCT04273425), patients with suspected MM requiring a diagnostic iliac crest biopsy at Sheffield Teaching Hospital (UK) are invited to participate. Consenting patients answer seven standardized questionnaires assessing pain, quality of life and catastrophizing. Bone turnover biomarkers and inflammatory cytokines are measured in fasting serum samples, and bone innervation is evaluated in diagnostic biopsies. MM patients are invited to a follow-up upon completion of first line treatment. This will be the first deep characterization of pain in MM patients and its correlation with disturbances in bone innervation. Understanding how bone turnover and inflammation correlate to pain in MM is crucial to identify novel analgesic targets for this condition.

Hospitalization at the End of Life in Myeloma Patients: Lessons from the National Inpatient Sample

INTRODUCTION: Multiple myeloma (MM) remains a largely incurable disease, and despite the variety of treatment options available, duration of response decreases with each subsequent line of therapy resulting in refractory disease . In this setting, studies have shown most patients prefer to die in the comfort of home, yet hospitalizations remain frequent at the end of life. We explored the hospitalization burden of MM patients at the end of their life using the National Inpatient Sample (NIS). METHODS: The NIS is a database that provides information on all inpatient hospitalizations in the United States (US), including primary and secondary diagnoses, procedures, length of stay, and disposition. Approximately 20% of admissions are tracked and weighted estimates are provided regarding the total number of hospitalizations. Using the NIS, we tracked hospital admissions for MM patients and inpatient mortality from 2002 to 2014 via procedural International Classification of Disease (ICD) 9 codes to gain insight into trends in transfusions, infectious complications, and cost of admission. Linear regression modeling was used for analysis. Overall annual number of deaths for MM in the United States was obtained from publicly available reports from the Centers for Disease Control (CDC) and Prevention and the National Cancer Institute (NCI). RESULTS: During the time period 2002-2014, the CDC and NCI reported a total of 144,105 deaths from MM, ranging from 10,913 in 2002 to 12,112 in 2014. The NIS identified a total of 233,932 (non-weighted) hospitalizations for MM during this time period. Amongst these, a total of 14,770 (non-weighted) hospitalizations resulted in death, thus 6.3% of all hospitalizations for myeloma patients resulted in death. A weighted sample of 69,825 hospitalizations resulting in deaths were identified. During our study time period, 48.4% of all deaths related to myeloma in the United States occurred in the hospital, ranging from 5,893 (54%) in 2002 to 5,035 (41.6%) in 2014, p<0.01. We analyzed blood transfusion dependency in the hospitalization leading to death. There was a receipt of blood transfusions (35.8%) in 5,285 of the 14,770 (non-weighted) admissions leading to death. Infection frequency was identified using the Clinical Classification Software. The Clinical Classifications Software (CCS) is a tool that allows for clustering patient diagnoses and procedures into clinically meaningful categories. A total of 6,644 infections were identified amongst the 14,770 (non-weighted) hospitalizations leading to death (45.0%). We then analyzed palliative care/hospice involvement during the hospitalization leading to death over time. Palliative care/hospice was consulted in 67 of the 1260 (non-weighted) hospitalizations in 2002 (5.3%), and 338 out of the 1007 (non-weighted) hospitalizations in 2014 (33.57%), p<0.01. Median cost of the hospitalization leading to death increased over time from $48,709 in 2002 to $104,115 in 2014, p<0.01. CONCLUSIONS: Despite a decrease in the percentage of inpatient deaths over time, greater than 40% of patients with myeloma continue to die in the hospital, with significant transfusion requirements and infections at the end of life. This comes with an increased cost to the health care system. Our analysis suggests that while palliative care involvement at the end of life has also increased over time, earlier involvement of palliative care and incorporation of transfusion support within hospice services may decrease the number of myeloma patients dying in the hospital and, therefore, the overall burden and cost of care. Disclosures No relevant conflicts of interest to declare.

An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma

ABSTRACT Introduction A subcutaneous formulation of daratumumab, a human immunoglobulin G1 kappa monoclonal antibody targeting CD38, recently achieved FDA approval for both newly diagnosed and relapsed refractory multiple myeloma amid promises to decrease infusion times and rates of infusion reactions in myeloma patients. Areas covered In this article the biology behind subcutaneous administration of oncologic antibody therapies is reviewed and the subcutaneous formulation of daratumumab is covered in depth. The most recent results from the PAVO, COLUMBA, and PLEIADES clinical trials evaluating subcutaneous daratumumab as a single agent, and in combination, in both newly diagnosed, and relapsed and refractory myeloma patients are summarized. The efficacy, safety, and PK data from these trials are reviewed, and the potential of the subcutaneous formulation to improve quality of life in myeloma patients and decrease healthcare resource use is discussed. Expert opinion Subcutaneous daratumumab is non-inferior to conventional intravenous daratumumab with lower risk of infusion-related reactions and decreased administration time. Based on these data, and the recent FDA and European Commission approvalsthe widespread use of the subcutaneous formulation for both conventional and investigational practice is supported.

The mediator role of unmet needs on quality of life in myeloma patients.

The diagnosis of multiple myeloma (MM) has a significant impact on patients. This study analyzed the mediating role of patients' unmet needs in the relationship between psychological morbidity/social support and quality of life (QoL). This study included 213 patients with MM recruited from the outpatient medical oncology and clinical hematology services from five hospitals. Patients who meet the study criteria were referred by physicians and invited to participate in the study by the researcher. All participants answered the following questionnaires: Hospital Anxiety and Depression Scale, Satisfaction with Social Support Scale, Short-Form Survivor Unmet Needs Survey, and The European Organization for Research and Treatment of Cancer's Multiple Myeloma Module. Descriptive statistics, bivariate correlations, and structural equation modeling were performed to analyze the data. The indirect effect of psychological morbidity on patients' future perspectives (MYFP) was partially mediated by information unmet needs (INF), while the indirect effect of psychological morbidity on treatment side effects (MYSE) was partially mediated by relationship and emotional unmet needs (REH). In turn, the indirect effect of psychological morbidity on disease symptoms (MYDS) was fully mediated by REH. Social support had an indirect effect on MYDS and MYSE fully mediated by REH. Intervention programs tailored to promote MM patients' QoL should specifically address information and emotional needs, raising awareness and training health professionals, caregivers, and family membersto attend MMpatients' unmet needs.

Assessment of Quality of Life in Myeloma Patients Post Autologous Stem Cell Transplant- A Single Centre Experience in South India

Assessment of Quality of Life in Myeloma Patients Post Autologous Stem Cell Transplant- A Single Centre Experience in South India

Reliability and Validity of an Iranian Version of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Patients with Multiple Myeloma: the EORTC QLQ-MY20

Reliable and validated instruments are needed in order to study the quality of life in myeloma patients. This study aimed to translate and explore the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) myeloma module (QLQ-MY20) in Iranian patients. Two hundred and fifteen patients with multiple myeloma (MM) were recruited from Imam Khomeini Hospital, Tehran. A standard forward-backward translation procedure was implemented. Participating patients were asked to complete the EORTC QLQ-C30 and the QLQ-MY20 three times, at study entry, after two weeks, and again after three months. Data were tested for the range of measurement, internal consistency, test-retest reliability, known group comparison, responsiveness and factor structure. Mean age of the patients was 60.7 years. No floor and ceiling effects were seen for the QLQ-MY20. Cronbach's α was greater than 0.80 for all three multi-item scales (ranging from 0.82 to 0.93). All four scales had test-retest reliability of 0.85 or greater. Results of the confirmatory factor analysis that the hypothesized 3-scale measurement model of the QLQ-MY20. Moreover, the Persian version for the QLQ-MY20 differentiated between subgroups of the patients in terms of beta-2 microglobulin, fracture and performance status. The responsiveness of the QLQ-MY20 to change over time was confirmed within 3 months. the results of our study indicate that our Iranian version of the QLQ-MY20 is a feasible, reliable and valid questionnaire for assessing the condition-specific quality of life of patients with MM.

Novel Induction Regimens in Multiple Myeloma.

Multiple myeloma is the second most common hematologic malignancy and predominantly affects the elderly. The introduction of novel agents such as thalidomide, lenalidomide, and bortezomib has improved progression-free survival, overall survival, and quality of life in myeloma patients. Next generation agents such as carfilzomib hold further promise for increased depth and length of remission. Autologous stem cell transplant remains a useful tool in the treatment of multiple myeloma, but not all patients are eligible for this procedure. As therapy becomes more effective, determination of the right therapy in the right patient becomes paramount. The focus of this review is a critical analysis of combinations of the novel agents in the treatment of newly diagnosed multiple myeloma in both transplant eligible and ineligible patients.

Induction of CXCL1 in Osteoblasts by Myeloma Cells Promotes Migration of Osteoclast Precursors

AbstractAbstract 441 IntroductionMultiple myeloma (MM) causes a dysbalance in the bone microenvironment between bone building osteoblasts and bone resorbing osteoclasts (OCs), with an increase in OC recruitment, differentiation and activation, leading to myeloma bone disease (MBD). Presence of MBD has a major impact on the quality of life of MM patients and novel treatment approaches for MBD are urgently needed. Several factors have been identified that play a role in this process, e.g. receptor activator of NF-kB ligand (RANKL). However, the pathomechanism of increased osteoclast recruitment and activation is not completely understood. Here, we investigated the role of the chemokine CXCL1 and its receptor CXCR2 in the bone microenvironment in MM. Material and MethodsSerum samples from 52 patients with newly diagnosed MM and from 22 healthy volunteers were assayed using a CXCL1 ELISA. Primary human mesenchymal stem cells (hMSCs) were cultured from bone marrow aspirates and primary human differentiated osteoblasts (hOBs) were cultured from trabecular bone fragments, both from healthy volunteers. Osteoclast precursors (pre-OCs) were generated by immunomagnetic sorting of CD14-positive cells from the peripheral blood of healthy volunteers. Human myeloma cell lines (HMCLs) U-266, RPMI-8226 and LP-1 and primary bone marrow myeloma cells (pMMCs) selected using CD138 immunomagnetic sorting were used for the experiments. Co-cultures of HMCLs and pMMCs with hMSCs or hOBs were performed using 0.45 μm transwell inserts, allowing for the exchange of soluble mediators. Migration assays were performed using 8 μm transwell inserts and human recombinant CXCL1. Immunohistochemistry was performed on paraffin-embedded bone marrow biopsies from MM patients using an anti-CXCR2 monoclonal antibody. All experimental procedures involving patient material were approved by the local ethics committee and conducted after informed consent was obtained. ResultsCXCL1 serum levels were found to be significantly higher in MM patients than in healthy individuals (193.4 pg/mL vs. 137 pg/mL, respectively, p<0.05), indicating a role for CXCL1 in MM pathophysiology. We went on to investigate the role of CXCL1 in MBD and performed co-cultures of HMCLs and pMMCs with hMSCs or hOBs. Baseline CXCL1 expression was absent in HMCLs and low or absent in hMSCs or hOBs at baseline. RNA expression as well as protein excretion by hMSCs and hOBs were induced after co-culture with myeloma cells. For example, pMMCs from different individuals led to a mean 154-fold upregulation of CXCL1 mRNA levels in hMSCs and to a mean upregulation of CXCL1 protein in cell culture supernatants from <31.5 pg/mL at baseline to 2140 pg/mL after co-cultures. In order to investigate the potential function of elevated CXCL1 levels in the bone marrow microenvironment, the expression of CXCR2, the receptor for CXCL1, was analyzed. Pre-OCs as well as a majority of pMMCs expressed CXCR2 mRNA. CXCR2 protein expression in pMMCs was verified using immunohistochemistry on MM bone marrow biopsies. Human recombinant CXCL1 significantly increased pre-OC cell migration in a dose-dependent manner. For example, 50 ng/mL or 100 ng/mL of CXCL1 increased mean pre-OC migration along a CXCL1 gradient 2.5-fold and 5.6-fold over baseline, respectively. In addition, mean pMMC migration was increased 3.8-fold compared to baseline along a 100 ng/mL gradient of recombinant CXCL1. The osteoclastogenic capacity of the migrated pre-OCs was confirmed by TRAP expression after stimulation with RANKL and M-CSF. ConclusionWe describe here a novel role for the chemokine CXCL1 in myeloma bone disease. We demonstrate that CXCL1 is induced in hMSCs and hOBs by co-culture with MM cells. CXCL1 leads to chemoattraction of both pre-OCs and pMMCs. These effects could lead to co-localization of OCs and MM cells in the bone marrow microenvironment and contribute to the tumor-promoting interaction between these cell types. Our data indicate the CXCL1-CXCR2 axis as a therapeutic target in myeloma bone disease. Disclosures:No relevant conflicts of interest to declare.

The International Myeloma Foundation

Imagine experiencing backpain so severe, it kept you in bed for weeks at a time. What if someone told you that you could no longer pick up your child or tightly embrace loved ones out of fear of breaking a bone? Imagine knowing that your symptoms could worsen to a point where you might become completely debilitated and that modern medicine, in all its breakthroughs, held no cure. Imagine that you have just been diagnosed with multiple myeloma. Multiple myeloma is a little-known, devastating cancer of the bone marrow for which there is no known cure. Multiple myeloma affects approximately 75,000 to 100,000 people in the United States, and with more than 15,000 new cases diagnosed each year, is one of the fastest-growing cancers in the Western world. Despite its high numbers and devastating effects, the public — both patients and physicians — remains largely unaware of myeloma. As a result, patients can go mis- or undiagnosed for years. The International Myeloma Foundation (IMF) is a non-profit organization dedicated to the education, research, and treatment of multiple myeloma. It was founded in 1990 by Brian and Susie Novis, along with hematologist/oncologist Dr. Brian G.M. Durie, directly following Brian Novis' myeloma diagnosis at the age of 33. Because little information on myeloma was available at the time, the IMF was established to meet the educational and emotional needs of myeloma patients and their families, while funding research in the search for a cure. The IMF was the first organization dedicated solely to multiple myeloma. Today, with a worldwide membership of more than 75,000, the IMF has grown to become the most comprehensive source of information and support programs for the myeloma community. The IMF is guided by a distinguished Scientific Advisory Board comprised of 37 medical experts who are internationally recognized as leaders in the field of multiple myeloma. In keeping with its mission of improving the quality of life for myeloma patients while working toward prevention and a cure, the IMF provides a complete array of education and support programs and services including the following.