Characteristics and Treatment Patterns of Long-surviving Patients With Multiple Myeloma: Over 13 Years of Follow-up in the Connect MM Registry.

Background: Over the last 15 years, improvements in patient management and treatments have been associated with longer survival in patients with multiple myeloma (MM). The Connect MM Registry is a long-running, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM (NDMM). We assessed the demographics, clinical characteristics, and treatment patterns of long-term survivors (LTS) enrolled in this registry.

Impact of lenalidomide-bortezomib-dexamethasone induction on patients with newly diagnosed multiple myeloma and renal impairment: Results from the Connect® MM Registry.

Limited data exist on the effects of induction treatment in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI), who may also be ineligible for autologous stem cell transplant. This analysis investigated the impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on renal function in patients from the Connect® MM Registry based on transplant status. Eligible patients were aged ≥18 years with symptomatic MM diagnosed ≤2 months before enrollment.

The Effect of Age and Other Patient Characteristics on Outcomes Among Nontransplanted Patients Who Were Treated With First-Line Lenalidomide, Bortezomib, and Dexamethasone: Results From the Connect MM Registry.

Background: Lenalidomide (R), bortezomib (V), and dexamethasone (d) is a standard-of-care regimen in newly diagnosed multiple myeloma (NDMM); however, characteristics and outcomes for nontransplanted patients receiving frontline RVd are not well understood.

Patients: The Connect MM Registry is a large, US, multicenter, prospective observational cohort study of NDMM patients.

Methods: This analysis investigated characteristics and outcomes of patients who received RVd alone or followed by Rd or R (RVd ± Rd/R) who did not undergo frontline autologous stem cell transplantation.

High-dose chemotherapy and peripheral blood stem cell transplantation as salvage therapy in primary mediastinal nonseminomatous germ cell tumors: The Indiana University experience.

Background: Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high-dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University.

Methods: The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first-line cisplatin-based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021.

1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma.

Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers can be identified.

Impact of prior lenalidomide or proteasome inhibitor exposure on the effectiveness of ixazomib-lenalidomide-dexamethasone for relapsed/refractory multiple myeloma: A pooled analysis from the INSURE study.

Objectives: To characterize the impact of prior exposure and refractoriness to lenalidomide or proteasome inhibitors (PIs) on the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM).

Methods: INSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA-IXA, and REMIX.

Results: Overall, 391/100/68 were lenalidomide-naïve/-exposed/-refractory and 37/411/110 were PI-naïve/-exposed/-refractory.

Real-World Utilization of Radiation Therapy in Multiple Myeloma: An Analysis of the Connect MM Registry.

Purpose: Radiation therapy (RT) is an important treatment modality for patients with multiple myeloma (MM). Although patients are living longer with MM, they are more likely to have comorbidities related to treatment, such as bone pain; however, RT can provide symptom relief. To date, the characterization of patients who have received RT in the real-world setting has been limited.

-class transition from bortezomib-based therapy to IRd is an effective approach in newly diagnosed multiple myeloma.

To compare the effectiveness of -class transition to all-oral ixazomib-lenalidomide-dexamethasone (IRd) following parenteral bortezomib (V)-based induction versus continued V-based therapy in US oncology clinics. Non-transplant eligible patients with newly diagnosed multiple myeloma (MM) receiving transition to IRd (N = 100; US MM-6), or V-based therapy (N = 111; INSIGHT MM). Following inverse probability of treatment weighting, overall response rate was 73.

Using a Modified Delphi Panel to Estimate Health Service Utilization for Patients with Advanced and Non-Advanced Systemic Light Chain Amyloidosis.

Purpose: Patients with diagnosed with systemic light chain (AL) amyloidosis at advanced Mayo stages have greater morbidity and mortality than those diagnosed at non-advanced stages. Estimating service use by severity is difficult because Mayo stage is not available in many secondary databases. We used an expert panel to estimate healthcare utilization among advanced and non-advanced AL amyloidosis patients.

Identifying novel mechanisms of biallelic TP53 loss refines poor outcome for patients with multiple myeloma.

Biallelic TP53 inactivation is the most important high-risk factor associated with poor survival in multiple myeloma. Classical biallelic TP53 inactivation has been defined as simultaneous mutation and copy number loss in most studies; however, numerous studies have demonstrated that other factors could lead to the inactivation of TP53. Here, we hypothesized that novel biallelic TP53 inactivated samples existed in the multiple myeloma population.

Identifying 1q amplification and PHF19 expressing high-risk cells associated with relapsed/refractory multiple myeloma.

Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers have been identified.

Maintenance Oral Etoposide After High-Dose Chemotherapy (HDCT) for Patients With Relapsed Metastatic Germ-Cell Tumors (mGCT).

Background: HDCT and peripheral-blood stem-cell transplant (PBSCT) can cure up to 60% of pts with relapsed mGCT. Maintenance daily oral etoposide after salvage therapy has demonstrated potential clinical benefit. We now evaluate the potential role of maintenance etoposide versus observation post HDCT+PBSCT in this nonrandomized retrospective analysis.

Rates of Influenza and Pneumococcal Vaccination and Correlation With Survival in Multiple Myeloma Patients.

Background: Infections are a common reason for hospitalization and death in multiple myeloma (MM). Although pneumococcal vaccination (PV) and influenza vaccination (FV) are recommended for MM patients, data on vaccination status and outcomes are limited in MM.

Materials And Methods: We utilized data from the global, prospective, observational INSIGHT MM study to analyze FV and PV rates and associated outcomes of patients with MM enrolled 2016-2019.

Treatment Patterns, Survival, Quality of Life, and Healthcare Resource Use Among Patients With Triple-Class Refractory Multiple Myeloma in US Clinical Practice: Findings From the Connect MM Disease Registry.

Background: Adults with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognosis, but the burden of TCR MM has not been well characterized. This study evaluated treatment patterns, overall survival (OS), health-related quality of life (HRQoL), and healthcare resource use (HCRU) among patients with TCR MM in US clinical practice.

Patients And Methods: Patients with TCR MM in the Connect MM Registry (NCT01081028; a large, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM) were included.

High-dose chemotherapy for relapsed testicular germ cell tumours.

Relapsed testicular germ cell tumours (GCTs) might be cured with salvage chemotherapy. Accepted salvage treatment is conventional-dose chemotherapy (CDCT) or high-dose chemotherapy (HDCT). HDCT with peripheral blood stem cell transplant might produce a higher number of durable responses than CDCT.

Real-world treatment patterns, costs, and outcomes in patients with AL amyloidosis: analysis of the Optum EHR and commercial claims databases.

Background: This study characterised real-world treatment patterns, clinical outcomes, and cost-of-illness in patients with light-chain (AL) amyloidosis.

Methods: Data were extracted from the US-based Optum® EHR and Clinformatics® Data Mart (claims) databases (2008-2019) for patients newly diagnosed with AL amyloidosis and who initiated anti-plasma cell therapies. Healthcare resource utilisation (HCRU) and related costs were compared across lines of therapy (LOT).

Myeloma Genome Project Panel is a Comprehensive Targeted Genomics Panel for Molecular Profiling of Patients with Multiple Myeloma.

Purpose: We designed a comprehensive multiple myeloma targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards.

Experimental Design: The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNA). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical FISH (translocations), multiplex ligation probe analysis (MLPA; CNAs), whole-genome sequencing (WGS; CNAs, mutations, translocations), or droplet digital PCR (ddPCR) of known standards (mutations).

ASTCT Clinical Practice Recommendations for Transplantation and Cellular Therapies in Multiple Myeloma.

Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape.

Effect of t (11;14) Abnormality on Outcomes of Patients With Newly Diagnosed Multiple Myeloma in the Connect MM Registry.

Background: The t (11;14) (q13;32) translocation [t (11;14)] is present in ∼20% of patients with newly diagnosed multiple myeloma (NDMM), but studies examining its prognostic ability have yielded divergent results, and data are lacking on outcomes from first-line therapy.

Patients And Methods: Data from the Connect MM Registry, a large US, multicenter, prospective observational cohort study of patients with NDMM were used to examine the effect of t (11;14) status on first-line therapy outcomes in the Overall population (n = 1574) and race groups (African American [AA] vs. non-African American [NAA]).

Survival outcomes and toxicity in patients 40 years old or older with relapsed metastatic germ cell tumors treated with high-dose chemotherapy and peripheral blood stem cell transplantation.

Background: High-dose chemotherapy (HDCT) plus peripheral blood stem cell transplantation (PBSCT) is effective salvage therapy for relapsed metastatic germ cell tumors (GCTs) but has potential toxicity. Historically, an age of ≥40 years has been associated with greater toxicity and worse outcomes.

Methods: This is a retrospective analysis of 445 consecutive patients with relapsed GCT treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen.

Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US.

Multiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM.

Cryopreservation Preserves Cell-Type Composition and Gene Expression Profiles in Bone Marrow Aspirates From Multiple Myeloma Patients.

Single-cell RNA sequencing reveals gene expression differences between individual cells and also identifies different cell populations that are present in the bulk starting material. To obtain an accurate assessment of patient samples, single-cell suspensions need to be generated as soon as possible once the tissue or sample has been collected. However, this requirement poses logistical challenges for experimental designs involving multiple samples from the same subject since these samples would ideally be processed at the same time to minimize technical variation in data analysis.

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma.

To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed. At data cut-off, 263 patients from 13 countries were included.

Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease.

Background: Dipeptidyl peptidase 4 (DPP-4; also known as CD26), a transmembrane receptor expressed on T cells, has a costimulatory function in activating T cells. In a mouse model, down-regulation of CD26 prevented graft-versus-host disease (GVHD) but preserved graft-versus-tumor effects. Whether inhibition of DPP-4 with sitagliptin may prevent acute GVHD after allogeneic stem-cell transplantation is not known.