State-of-the-Art Management of Complications of Myeloma and Its Treatment

Multiple myeloma is an incurable disease, although patient survival has increased with the availability of novel agents. Both multiple myeloma and its therapies often affect the renal, immune, skeletal, hematologic, and nervous systems. The resulting organ dysfunctions often impair the quality of life of affected patients, complicate and limit subsequent therapies, and may result in significant mortality. Research on the treatment of complications of multiple myeloma has been limited; hence, preventative and management strategies for patients with these complications are heterogeneous and often based on anecdotal experience. In this paper, we review the effects of myeloma and the novel therapies on organ systems and suggest management strategies

ABNORMALITIES OF THE GYRAL WINDOW IN AUTISM: A MACROSCOPIC CORRELATE TO A PUTATIVE MINICOLUMNOPATHY

Autism is a neurodevelopmental disorder characterized by impairments in social interaction, language, and range of interests. Recent studies suggest that the brains of autistic patients have an increased number of minicolumns. This finding helps explain the presence of macroencephaly or increased brain size in a significant proportion of autistic patients. Changes in brain size and gyrification are usually concurrent. In this study we have implemented an algorithm that measured the gyrification window in the brains of 23 postmortem autistic and 16 postmortem control brains. At the 85% confidence level the algorithm correctly classified 22/23 autistics, a 0.96 accuracy rate, and 15/16 controls, a 0.94 accuracy rate. Previous structural neuroimaging studies in autism have emphasized volumetric measures. These methodologies are very sensitive to segmentation artifacts, being compromised by image noise, lack of strong edges, and sharing of color/texture among different structures. The present study offers a new approach to the classification of autism based on structural MRI.The finding bears relevance to the clinical presentation of autism as increased gyrification reduces the gyral window and constrains connectivity in favor of short corticocortical fibers

Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials

Renal impairment (RI) is a major comorbidity in patients with multiple myeloma (MM). Here we present the pooled safety and efficacy analysis of three clinical trials (MM-002, MM-003, and MM-010) of pomalidomide + low-dose dexamethasone (POM + LoDEX) in patients with moderate RI (creatinine clearance [CrCl] ≥ 30 to <60 mL/min) and without RI (≥ 60 mL/min). Trial protocols were approved by the institutional review board of each site involved. Patients with RI were older than patients without RI, although other baseline characteristics were similar. The dosing and safety profile of POM + LoDEX was similar across RI subgroups. Median overall response rate, progression-free survival, time to progression, and duration of response were not significantly different between RI subgroups. However, patients with vs. without RI had significantly shorter median overall survival (10.5 vs. 14.0 months, respectively; p = .004). This analysis demonstrates that POM + LoDEX is a safe and effective treatment for patients with moderate RI. The trials were registered at ClinicalTrials.gov as NCT00833833 (MM-002), NCT01311687 (MM-003), and NCT01712789 (MM-010) and at EudraCT as 2010-019820-30 (MM-003) and 2012-001888-78 (MM-010)

Twice‐weekly ixazomib in combination with lenalidomide‐dexamethasone in patients with newly diagnosed multiple myeloma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144661/1/bjh15394.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144661/2/bjh15394_am.pd

A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma

AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma (MM) cells. This phase 2 study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory MM

Whole-Exome sequencing analysis identified TMSB10/TRABD2A locus to be associated with carfilzomib-related cardiotoxicity among patients with multiple myeloma

BackgroundProteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis.MethodsExome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center. Separate analyses were performed in European Americans and African Americans followed by a trans-ethnic meta-analysis.ResultsThe most significant variant in the exome-wide single variant analysis was a missense variant rs7148 in the thymosin beta-10/TraB Domain Containing 2A (TMSB10/TRABD2A) locus. The effect allele of rs7148 was associated with a higher risk of CVAE [odds ratio (OR) = 9.3 with a 95% confidence interval of 3.9—22.3, p = 5.42*10−7]. MM patients with rs7148 AG or AA genotype had a higher risk of CVAE (50%) than those with GG genotype (10%). rs7148 is an expression quantitative trait locus (eQTL) for TRABD2A and TMSB10. The gene-based analysis also showed TRABD2A as the most significant gene associated with CFZ-CVAE (p = 1.06*10−6).ConclusionsWe identified a missense SNP rs7148 in the TMSB10/TRABD2A as associated with CFZ-CVAE in MM patients. More investigation is needed to understand the underlying mechanisms of these associations

State-of-the-Art Management of Complications of Myeloma and Its Treatment

Multiple myeloma is an incurable disease, although patient survival has increased with the availability of novel agents. Both multiple myeloma and its therapies often affect the renal, immune, skeletal, hematologic, and nervous systems. The resulting organ dysfunctions often impair the quality of life of affected patients, complicate and limit subsequent therapies, and may result in significant mortality. Research on the treatment of complications of multiple myeloma has been limited; hence, preventative and management strategies for patients with these complications are heterogeneous and often based on anecdotal experience. In this paper, we review the effects of myeloma and the novel therapies on organ systems and suggest management strategies