Disease Characteristics and Outcomes of 493 Young Myeloma Patients Treated With Modern Therapies: A Canadian Myeloma Research Group Database Study.

Background: Young patients ≤ 50 years old with multiple myeloma (MM) account for about 10% of cases and are underrepresented in the literature.

Methods: We explored disease characteristics, treatments, and outcomes following modern therapies of young MM patients using the Canadian Myeloma Research Group (CMRG) database. We included 493 patients ≤ 50 years old diagnosed with MM or plasma cell leukemia without concurrent amyloidosis or POEMS syndrome from January 1, 2010, to July 1, 2022.

Tandem Autologous Stem Cell Transplantation Does Not Benefit High-Risk Myeloma Patients in the Maintenance Era: Real-World Results from The Canadian Myeloma Research Group Database.

In patients with multiple myeloma (MM), the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant (ASCT) does benefit these patients. Tandem transplantation has been explored as a means to deepen responses and further improve survival however, its role remains controversial.

Long-term follow-up of outcomes including progression-free survival 2 in patients with transplant-ineligible multiple myeloma in the real-world practice: A multi-institutional report from the Canadian Myeloma Research Group (CMRG) database.

Multiple myeloma remains an incurable cancer mostly affecting older adults and is characterized by a series of remission inductions and relapses. This study aims to evaluate the outcomes in newly diagnosed transplant-ineligible patients using bortezomib/lenalidomide-based regimens in the Canadian real world as well as their outcomes in the second line. The Canadian Myeloma Research Group Database (CMRG-DB) is a national database with input from multiple Canadian Centres with now up to 8000 patients entered.

Redefining attrition in multiple myeloma (MM): a Canadian Myeloma Research Group (CMRG) analysis.

While most patients diagnosed with multiple myeloma (MM) receive initial therapy, reported attrition rates are high. Understanding attrition rates and characteristics of patients not receiving subsequent therapy is useful for MM stakeholders. We performed an analysis of attrition rates in a large disease-specific database of patients with newly diagnosed MM who received at least one line of therapy between Jan 1/10-Dec 31/20.

Carfilzomib usage patterns and outcomes in patients with relapsed multiple myeloma: A multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Carfilzomib is an active and commonly used treatment in patients with multiple myeloma (MM). Using the Canadian Myeloma Research Group Database, we performed a retrospective observational study of patients treated with carfilzomib for relapse of MM in a real-world setting in Canada between years 2007 and 2020. A total of 445 patients were included in this study: the doublet (Kd/p,  = 218) and triplets (KCd,  = 88; KRd,  = 99; KPd/p,  = 40).

Real-world data on lenalidomide dosing and outcomes in patients newly diagnosed with multiple myeloma: Results from the Canadian Myeloma Research Group Database.

Using the Canadian Myeloma Research Group Database, a retrospective study of 167 newly diagnosed, transplant-ineligible patients with multiple myeloma (MM) that received lenalidomide-dexamethasone as front-line treatment was conducted to understand the impact of lenalidomide dosing. Starting dose modifications were common, 42% of patients started on lenalidomide <25 mg with normal renal function. During treatment course, 35% of patients required further dose reduction.

Outcomes of daratumumab in the treatment of multiple myeloma: A retrospective cohort study from the Canadian Myeloma Research Group Database.

Daratumumab (dara) has significantly altered the therapeutic landscape of multiple myeloma (MM), especially in the relapsed setting. This study aimed to evaluate the outcomes of dara-containing regimens in the Canadian real-world setting among relapsed and refractory MM available within the national Canadian Myeloma Research Group Database (CMRG-DB). A total of 583 MM patients who received dara-based therapy in second-line or later treatment were included.

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database.

Background: Considerable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization.

Methods: The Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients.

Sequential Use of Carfilzomib and Pomalidomide in Relapsed Multiple Myeloma: A Report from the Canadian Myeloma Research Group (CMRG) Database.

The treatment of multiple myeloma has dramatically improved due to the availability of novel therapies that are highly effective and are quickly moving into first-line therapy. The Canadian Agency for Drugs and Technologies in Health (CADTH) recently recommended that patients who receive daratumumab should only be eligible to receive either carfilzomib or pomalidomide but not both, for relapsed MM. In order to assess the efficacy of these two agents in the relapsed setting, we utilized our national myeloma database.

Efficacy of Daratumumab-Containing Regimens Among Patients With Multiple Myeloma Progressing on Lenalidomide Maintenance: Retrospective Analysis.

Background: Daratumumab, a monoclonal antibody directed against CD38 is a recent class of drugs introduced into the multiple myeloma therapeutic landscape. While clinical trial data have shown a remarkable impact on outcomes, the efficacy of daratumumab combination therapies in specific clinically relevant subgroups including among patients refractory to lenalidomide maintenance remains unknown.

Methods: In this study, retrospective data were reviewed from the Canadian Myeloma Research Group and the German Munster Myeloma databases to identify patients that received daratumumab in combination with pomalidomide (DPd), lenalidomide (DRd), and bortezomib (DVd) in a population that had relapsed on lenalidomide maintenance postautologous stem cell transplant.

Retrospective study of treatment patterns and outcomes post-lenalidomide for multiple myeloma in Canada.

Lenalidomide is an important component of initial therapy in newly diagnosed multiple myeloma, either as maintenance therapy post-autologous stem cell transplantation (ASCT) or as first-line therapy with dexamethasone for patients' ineligible for ASCT (non-ASCT). This retrospective study investigated treatment patterns and outcomes for ASCT-eligible and -ineligible patients who relapsed after lenalidomide as part of first-line therapy, based on data from the Canadian Myeloma Research Group Database for patients treated between January 2007 and April 2019. Among 256 patients who progressed on lenalidomide maintenance therapy, 28.

Real-world outcomes with bortezomib-containing regimens and lenalidomide plus dexamethasone for the treatment of transplant-ineligible multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group database.

Bortezomib-containing regimens (BCRs) represented standard, first-line therapy for transplant-ineligible multiple myeloma (TIMM) in Canada until the introduction of lenalidomide and low-dose dexamethasone (Ld). However, little comparative data exist to inform the selection of regimens. We assessed the outcomes for TIMM patients treated with cyclophosphamide, bortezomib and dexamethasone or prednisone (CyBorD/P), bortezomib, melphalan and prednisone (VMP), bortezomib and dexamethasone or prednisone (VD/P) and lenalidomide and low-dose dexamethasone (Ld) using the Canadian Myeloma Research Group database.

The impact of lenalidomide maintenance on second-line chemotherapy in transplant eligible patients with multiple myeloma.

Objectives: To understand the impact of therapy sequencing on progression-free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low-dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting.

Methods: We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database.

Design of peptide mimetics to block pro-inflammatory functions of HA fragments.

Hyaluronan is a simple extracellular matrix polysaccharide that actively regulates inflammation in tissue repair and disease processes. The native HA polymer, which is large (>500 kDa), contributes to the maintenance of homeostasis. In remodeling and diseased tissues, polymer size is strikingly polydisperse, ranging from <10 kDa to >500 kDa.

Clinical Validation of Copy Number Variant Detection from Targeted Next-Generation Sequencing Panels.

Next-generation sequencing (NGS) technology has rapidly replaced Sanger sequencing in the assessment of sequence variations in clinical genetics laboratories. One major limitation of current NGS approaches is the ability to detect copy number variations (CNVs) approximately >50 bp. Because these represent a major mutational burden in many genetic disorders, parallel CNV assessment using alternate supplemental methods, along with the NGS analysis, is normally required, resulting in increased labor, costs, and turnaround times.

Effects of a Structured Exercise Program on Physical Activity and Fitness in Colon Cancer Survivors: One Year Feasibility Results from the CHALLENGE Trial.

Background: There is strong interest in testing lifestyle interventions to improve cancer outcomes; however, the optimal methods for achieving behavior change in large-scale pragmatic trials are unknown. Here, we report the 1-year feasibility results for exercise behavior change in the Canadian Cancer Trials Group CO.21 (CHALLENGE) Trial.

Carcinoma Cell Hyaluronan as a "Portable" Cancerized Prometastatic Microenvironment.

Hyaluronan (HA) is a structurally simple polysaccharide, but its ability to act as a template for organizing pericellular matrices and its regulated synthesis and degradation are key to initiating repair responses. Importantly, these HA functions are usurped by tumor cells to facilitate progression and metastasis. Recent advances have identified the functional complexities associated with the synthesis and degradation of HA-rich matrices.

Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a randomized, double-blind safety study comparing cetuximab produced from two manufacturing processes using the EXTREME study regimen.

Background: Cetuximab, in combination with platinum chemotherapy plus 5-fluoruracil (5-FU), is approved for the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Cetuximab manufactured by ImClone (US commercial cetuximab) potentially results in higher systemic exposures than cetuximab manufactured by Boehringer Ingelheim (BI-manufactured cetuximab). This prospective, randomized, double-blind study compared the safety profiles of the two cetuximab formulations.

Can CD44 Be a Mediator of Cell Destruction? The Challenge of Type 1 Diabetes.

CD44 is a multi-functional receptor with multiple of isoforms engaged in modulation of cell trafficking and transmission of apoptotic signals. We have previously shown that injection of anti-CD44 antibody into NOD mice induced resistance to type 1 diabetes (T1D). In this communication we describe our efforts to understand the mechanism underlying this effect.

Institutional clinical trial accrual volume and survival of patients with head and neck cancer.

Purpose: National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer (HNC) receive treatment at centers with expertise, but whether provider experience affects survival is unknown.

Patients And Methods: The effect of institutional experience on overall survival (OS) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group (RTOG 0129), which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy. As a surrogate for experience, institutions were classified as historically low- (HLACs) or high-accruing centers (HHACs) based on accrual to 21 RTOG HNC trials (1997 to 2002).

Stanniocalcin-1 inhibits renal ischemia/reperfusion injury via an AMP-activated protein kinase-dependent pathway.

AKI is associated with increased morbidity, mortality, and cost of care, and therapeutic options remain limited. Reactive oxygen species are critical for the genesis of ischemic AKI. Stanniocalcin-1 (STC1) suppresses superoxide generation through induction of uncoupling proteins (UCPs), and transgenic overexpression of STC1 inhibits reactive oxygen species and protects from ischemia/reperfusion (I/R) kidney injury.

Assessing cancer cell migration and metastatic growth in vivo in the chick embryo using fluorescence intravital imaging.

Cell migration and metastasis are key features of aggressive tumors. These processes can be difficult to study, as they often occur deep within the body of a cancer patient or an experimental animal. In vitro assays are able to model some aspects of these processes, and a number of assays have been developed to assess cancer cell motility, migration, and invasion.

RHAMM and CD44 peptides-analytic tools and potential drugs.

CD44 and RHAMM are two extracellar matrix receptors whose principle ligand is the polysaccharide hyaluronan (HA). Both proteins are involved in wound repair and their aberrant regulation contributes to a variety of diseases including arthritis and cancer. Over the past decade, a number of peptide-based therapeutics that block the binding of CD44 or RHAMM-specific ligands have been developed and tested in experimental models of disease.