Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6-89.6) years with a median of 3 prior lines (range 1-9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1-5.6) months and 13.3 (95% CI 10.6-16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6-5.3) months and 10.5 (95% CI 8.5-13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.

Lubricated Friction and the Hersey Number.

Most frictional contacts are lubricated in some way, but is has proven difficult to measure and predict lubrication layer thicknesses and assess how they influence friction at the same time. Here we study the problem of rigid-isoviscous lubrication between a plate and a sphere, both experimentally and theoretically. The liquid layer thickness is measured by a novel method using inductive sensing, while the friction is measured simultaneously. The measured values of the layer thickness and friction on the disk are well described by the hydrodynamic description of liquid flowing through a contact area. This allows us to propose a modified version of the Hersey number that compares viscous to normal forces and allows us to rescale data for different geometries and systems. The modification overcomes the shortcomings of the commonly used Hersey number, adds the effects of the geometry of the configuration on the friction, and successfully predicts the lubrication layer thickness.

Design and evaluation of an abbreviated pixelwise dynamic contrast enhancement analysis protocol for early extracellular volume fraction estimation.

INTRODUCTION: T1-based method is considered as the gold standard for extracellular volume fraction (ECV) mapping. This technique requires at least a 10 min delay after injection to acquire the post injection T1 map. Quantitative analysis of Dynamic Contrast Enhancement (DCE) images could lead to an earlier estimation of an ECV like parameter (2 min). The purpose of this study was to design a quantitative pixel-wise DCE analysis workflow to assess the feasibility of an early estimation of ECV. METHODS: Fourteen patients with mitral valve prolapse were included in this study. The MR protocol, performed on a 3 T MR scanner, included MOLLI sequences for T1 maps acquisition and a standard SR-turboFlash sequence for dynamic acquisition. DCE data were acquired for at least 120 s. We implemented a full DCE analysis pipeline with a pre-processing step using an innovative motion correction algorithm (RC-REG algorithm) and a post-processing step using the extended Tofts Model (ECVETM). Estimated ECVETM maps were compared to standard T1-based ECV maps (ECVT1) with both a Pearson correlation analysis and a group-wise analysis. RESULTS: Image and map quality assessment showed systematic improvements using the proposed workflow. Strong correlation was found between ECVETM, and ECVT1 values (r-square = 0.87). CONCLUSION: A DCE analysis workflow based on RC-REG algorithm and ETM analysis can provide good quality parametric maps. Therefore, it is possible to extract ECV values from a 2 min-long DCE acquisition that are strongly correlated with ECV values from the T1 based method.

Canadian perspective on managing multiple myeloma during the COVID-19 pandemic: lessons learned and future considerations.

The coronavirus disease 2019 (covid-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 has necessitated changes to the way patients with chronic diseases are managed. Given that patients with multiple myeloma are at increased risk of covid-19 infection and related complications, national bodies and experts around the globe have made recommendations for risk mitigation strategies for those vulnerable patients. Understandably, because of the novelty of the virus, many of the proposed risk mitigation strategies have thus far been reactionary and cannot be supported by strong evidence. In this editorial, we highlight some of the risk mitigation strategies implemented at our institutions across Canada during the first wave of covid-19, and we discuss the considerations that should be made when managing patients during the second wave and beyond.

A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis.

Despite improvements in therapy amyloid light-chain (AL) amyloidosis, there are few studies comparing different regimens. Here we present a matched comparison with 69 patients in each cohort examining upfront therapy with cyclophosphamide, bortezomib and dexamethasone (CVD) vs cyclophosphamide, thalidomide and dexamethasone (CTD). On an intention-to-treat basis, the overall response rates were 71.0% vs 79.7% in the CVD and CTD arms, respectively, (P=0.32). A higher complete response (CR) rate was observed in the CVD arm (40.5%) vs CTD (24.6%), P=0.046. One-year overall survival (OS) was 65.2% and 66.7% for CVD and CTD, respectively (P=0.87). The median progression-free survival (PFS) was 28.0 and 14.0 m for CVD and CTD, respectively (P=0.039). In a landmark analysis assessing outcomes performed at 6 months, the CR rate with CVD was 59.6% vs 34.0% for CTD (P=0.03). The 1-year OS was 96% with CVD and 92% with CTD (P=0.40). The median PFS with CVD was not reached and was 19.2 m with CTD, P=0.028). In summary, both regimens are unable to overcome the high rate of early deaths in AL amyloidosis. However, CVD correlates with improved depth of response and superior PFS supporting its use in the frontline setting. Further optimisation and better supportive-care strategies are required to increase the proportion of patients fully benefiting from therapy.

Clinical impact of somatic mosaicism in cases with small supernumerary marker chromosomes.

Somatic mosaicism is present in slightly more than 50% of small supernumerary marker chromosome (sSMC) carriers. Interestingly, non-acrocentric derived sSMC show mosaicism much more frequently than acrocentric ones. sSMC can be present in different mosaic rates, which may go below 5% of the studied cells. Also cryptic mosaicism can be present and mosaics may be differently expressed in different tissues of the body. Even though in the overwhelming majority of the cases somatic sSMC mosaicism has no direct clinical effect, there are also cases with altered clinical outcomes due to mosaicism. Also clinically important is the fact that a de novo sSMC, even present in mosaic, may be a hint of uniparental disomy (UPD). As it is under discussion to possibly replace standard karyotyping by methods like array-CGH, the impracticality of the latter to detect low-level sSMC mosaics and/or UPD has to be considered as well. Overall, sSMC mosaicism has to be studied carefully in each individual case, as it can be extremely informative and of importance, especially for prenatal genetic counseling.

Renal transplantation in systemic amyloidosis-importance of amyloid fibril type and precursor protein abundance.

Renal transplantation remains contentious in patients with systemic amyloidosis due to the risk of graft loss from recurrent amyloid and progressive disease. Outcomes were sought among all patients attending the UK National Amyloidosis Centre who received a renal transplant (RTx) between January 1978 and May 2011. A total of 111 RTx were performed in 104 patients. Eighty-nine percent of patients with end-stage renal disease (ESRD) due to hereditary lysozyme and apolipoprotein A-I amyloidosis received a RTx. Outcomes following RTx were generally excellent in these diseases, reflecting their slow natural history; median graft survival was 13.1 years. Only 20% of patients with ESRD due to AA, AL and fibrinogen amyloidosis received a RTx. Median graft survival was 10.3, 5.8 and 7.3 years in these diseases respectively, and outcomes were influenced by fibril precursor protein supply. Patient survival in AL amyloidosis was 8.9 years among those who had achieved at least a partial clonal response compared to 5.2 years among those who had no response (p = 0.02). Post-RTx chemotherapy was administered successfully to four AL patients. RTx outcome is influenced by amyloid type. Suppression of the fibril precursor protein is desirable in the amyloidoses that have a rapid natural history.