Citations

A new solution-phase DNA hybridization capture assay for the rapid detection of the mecA gene in clinical isolates of Staphylococcus was compared with multiplex PCR and disk diffusion methods. The assay uses a DNA capture probe immobilized on paramagnetic particles and a second DNA probe labeled with an acridinium ester. Bacteria from 24-h cultures are lysed, and the lysates are hybridized with the DNA probes. After magnetic separation to remove unhybridized labeled probe, the mecA gene is detected by the chemiluminescence of the hybridized probe. Four hundred consecutive staphylococcal isolates were assayed, including 147 S. aureus and 253 coagulase-negative Staphylococcus isolates. Among the S. aureus isolates, 14 of 147 were MecA+ by both the hybridization capture assay and PCR; 133 of 147 were MecA negative by both assays (positive and negative predictive values, 100%). Comparison of disk diffusion results with those obtained by genotypic methods indicated that 14 of 147 S. aureus isolates judged to be resistant were positive by both methods; 119 of 147 were Oxs and negative by both genotypic methods (positive and negative predictive values, 50 and 100%, respectively). The remaining 14 S. aureus isolates were MecA- Oxr; among these, 13 were beta-lactamase hyperproducers. For coagulase-negative staphylococci, 130 of 253 were MecA+ by the hybridization capture assay; 129 of 130 of these isolates were positive by PCR (positive and negative predictive values, 99.2 and 100%, respectively). Comparison with the disk diffusion assay showed that 128 of the coagulase-negative MecA+ isolates were Oxr; 111 of 253 were MecA- and Oxs (positive and negative predictive values, 90.8 and 99.1%, respectively). Thirteen coagulase-negative isolates were MecA-Oxr; among these, three were beta-lactamase hyperproducers. Comparison of the hybridization capture assay results with PCR indicates that the DNA hybridization assay is a sensitive and specific test for the detection of the mecA gene in clinical isolates of Staphylococcus.

Abstract A complex network precisely regulates the cell cycle through the G1, S, G2, and M phases and is the basis for cell division under physiological and pathological conditions. On the one hand, the transition from one phase to another as well as the progression within each phase is driven by the specific cyclin-dependent kinases (CDKs; e.g., CDK1, CDK2, CDK4, CDK6, and CDK7), together with their exclusive partner cyclins (e.g., cyclin A1, B1, D1–3, and E1). On the other hand, these phases are negatively regulated by endogenous CDK inhibitors such as p16ink4a, p18ink4c, p19ink4d, p21cip1, and p27kip1. In addition, several checkpoints control the commitment of cells to replicate DNA and undergo mitosis, thereby avoiding the passage of genomic errors to daughter cells. CDKs are often constitutively activated in cancer, which is characterized by the uncontrolled proliferation of transformed cells, due to genetic and epigenetic abnormalities in the genes involved in the cell cycle. Moreover, several oncogenes and defective tumor suppressors promote malignant changes by stimulating cell cycle entry and progression or disrupting DNA damage responses, including the cell cycle checkpoints, DNA repair mechanisms, and apoptosis. Thus, genes or proteins related to cell cycle regulation remain the main targets of interest in the treatment of various cancer types, including hematologic malignancies. In this context, advances in the understanding of the cell cycle regulatory machinery provide a basis for the development of novel therapeutic approaches. The present article summarizes the pathways as well as their genetic and epigenetic alterations that regulate the cell cycle; moreover, it discusses the various approved or potential therapeutic targets associated with the cell cycle, focusing on hematologic malignancies.

Abstract There is a need for new approaches and endpoints in oncology drug development, particularly with the advent of immunotherapies and the multiple drug combinations under investigation. Tumor dynamics modeling, a key component to oncology “model-informed drug development,” has shown a growing number of applications and a broader adoption by drug developers and regulatory agencies in the past years to support drug development and approval in a variety of ways. Tumor dynamics modeling is also being investigated in personalized cancer therapy approaches. These models and applications are reviewed and discussed, as well as the limitations and issues open for further investigations. A close collaboration between stakeholders like clinical investigators, statisticians, and pharmacometricians is warranted to advance clinical cancer therapeutics.

Aims We sought to investigate the association of obesity and metabolic health status with the incidence of clinical hypertrophic cardiomyopathy (HCM) diagnosis in the general population. Our goal was to identify modifiable risk factors to attenuate clinical expression of HCM, enabling management evolution from a mostly passive strategy of risk stratification to a proactive strategy of modifying disease expression. Methods Using nationwide population-based data from the Korean National Health Insurance Service, 28,679,891 people who were free of prevalent HCM and who underwent health examinations between 2009 and 2015 were followed until 31 December 2016. The primary outcome was clinical HCM that was defined as incident diagnosis of HCM during the follow-up, after a blanking period of 12 months. Results Over a median follow-up of 5.2 years, 0.027% (n = 7851) of the study participants were diagnosed as incident HCM. The incidence rate per 1000 person-years was 0.059. A significant association was found between body mass index (BMI) and the incidence of clinical HCM after multivariate adjustment, with a hazard ratio per 1 kg/m2 increase in BMI of 1.063 (95% confidence interval 1.051–1.075). Metabolically unhealthy participants had a greater incidence of HCM than metabolically healthy participants, regardless of obesity status. The effect of BMI was more pronounced in several subgroups, including participants with no hypertension, those aged less than 65 years and men. Conclusion We found that individuals with obesity and/or metabolic abnormalities had a significantly higher incidence of clinical HCM diagnosis than their counterparts. Efforts to manage obesity and metabolic abnormalities may be important in modifying clinical expression of HCM.

Goals: The study aimed to compare the level and characteristics of disease-related knowledge of patients with inflammatory bowel disease (IBD) between the West and the East using an international version of a questionnaire regarding knowledge of inflammatory bowel disease (IBD-KNOW). Background: The authors recently developed a new questionnaire regarding IBD-KNOW, which showed excellent test characteristics in Korea. Study: The IBD-KNOW questionnaire was administered to 100 patients with IBD from tertiary referral hospitals in the United States and Korea. Scores were calculated and compared between US and Korean patients, and factors associated with high scores were analyzed. Results: A total of 196 (100 US and 96 Korean) patients with IBD completed the questionnaires. Analysis of the baseline characteristics revealed that male sex, smoking status, disease duration, history of IBD-related operations, family history of IBD, and use of corticosteroids or biologics were significantly different between US and Korean patients. The mean IBD-KNOW score was higher in US patients than in Korean patients (14.8 vs. 11.3; P<0.001). Multivariate analyses showed that a high IBD-KNOW score (top 25%) was associated with a positive family history of IBD (odds ratio, 2.90; P=0.025) in US patients with IBD and with the use of biologics (odds ratio, 3.65; P=0.008) in Korean patients with IBD. Conclusions: The IBD-KNOW questionnaire, an updated assessment tool of IBD-related knowledge, is simple, reliable, and available in various patient populations. IBD-KNOW can be used to identify the factors affecting the level of IBD-related knowledge to improve the quality of care in patients with IBD through a personalized approach.

SummaryBackgroundThe Food and Drug Administration has approved several pharmacotherapies for the treatment of obesity. This study assesses the cost‐effectiveness of six pharmacotherapies and lifestyle intervention for people with mild obesity (body mass indices [BMIs] 30 to 35).MethodsA microsimulation model was constructed to compare seven weight loss strategies plus no treatment: intensive lifestyle intervention, orlistat, phentermine, phentermine/topiramate, lorcaserin, liraglutide, and semaglutide. Weight loss, quality‐of‐life scores, and costs were estimated using clinical trials and other published literature. Endpoints included costs, quality‐adjusted life years (QALYs), and incremental cost‐effectiveness ratios (ICERs) with a willingness‐to‐pay (WTP) threshold of $100 000/QALY. Results were analysed at 1‐, 3‐, and 5‐year time horizons.ResultsAt each of the three follow‐up periods, phentermine was the cost‐effective strategy, with ICERs of $46 258/QALY, $20 157/QALY, and $17 880/QALY after 1, 3, and 5 years, respectively. Semaglutide was the most effective strategy in the 3‐ and 5‐year time horizons, with total QALYs of 2.224 and 3.711, respectively. However, the ICERs were prohibitively high at $1 437 340/QALY after 3 years and $576 931/QALY after 5 years. Deterministic and probabilistic sensitivity analyses indicated these results were robust.ConclusionsPhentermine is the cost‐effective pharmacologic weight‐loss strategy. Although semaglutide is the most effective, it is not cost‐effective because of its high price.

Biliary complications (strictures and leaks) represent major limitations in living donor liver transplantation. Mesenchymal stem cells (MSCs) are a promising modality to prevent biliary complications because of immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose‐derived MSC delivery to biliary anastomoses in a porcine model. Secondary objectives were defining the optimal method of delivery (intraluminal versus extraluminal) and to investigate MSC engraftment, angiogenesis, and fibrosis. Pigs were divided into 3 groups. Animals underwent adipose collection, MSC isolation, and expansion. Two weeks later, animals underwent bile duct transection, reanastomosis, and stent insertion. Group 1 received plastic stents wrapped in unseeded Vicryl mesh. Group 2 received stents wrapped in MSC‐seeded mesh. Group 3 received unwrapped stents with the anastomosis immersed in an MSC suspension. Animals were killed 1 month after stent insertion when cholangiograms and biliary tissue were obtained. Serum was collected for liver biochemistries. Tissue was used for hematoxylin‐eosin and trichrome staining and immunohistochemistry for MSC markers (CD44 and CD34) and for a marker of neoangiogenesis (CD31). There were no intraoperative complications. One pig died on postoperative day 3 due to acute cholangitis. All others recovered without complications. Cholangiography demonstrated no biliary leaks and minimal luminal narrowing. Surviving animals exhibited no symptoms, abnormal liver biochemistries, or clinically significant biliary stricturing. Group 3 showed significantly greater CD44 and CD34 staining, indicating MSC engraftment. Fibrosis was reduced at the anastomotic site in group 3 based on trichrome stain. CD31 staining of group 3 was more pronounced, supporting enhanced neoangiogenesis. In conclusion, adipose‐derived MSCs were safely applied to biliary anastomoses. MSCs were locally engrafted within the bile duct and may have beneficial effects in terms of fibrosis and angiogenesis.

Abstract Introduction: Current advances in allogeneic hematopoietic cell transplant (alloHCT) may warrant a paradigm shift in managing children with sickle cell disease (SCD). This study characterizes the clinical outcomes and health care utilization (HCU) of alloHCT for pediatric SCD. We hypothesize that early alloHCT will have improved clinical outcomes, and decreased HCU. Methods: The Center for International Blood and Marrow Transplant Research database was used to identify children 21 years or less with alloHCT for SCD in the United States. Patient data included comprehensive research forms (CRF) from 2000-13 and transplant essential data (TED) forms from 2000-11. CRFs provided clinical risk factors associated with overall survival, graft failure, grade III-IV acute GVHD, and GVHD related event free survival (GREFS) - the survival free of graft failure, chronic GVHD, or death. Risk factors included age, gender, performance status, year of alloHCT, prior SCD complications and therapy, CMV status, donor type, conditioning regimen, and GVHD prophylaxis. Due to low event rates and sample size, only univariate analysis of risk factors was performed. TED data was merged with Pediatric Health Information System (PHIS) inpatient data using a probabilistic merging algorithm to determine risk factors and clinical outcomes associated with HCU. Available PHIS adjusted cost data was used to determine the total adjusted cost for all inpatient admissions per patient per hospital day. To standardize these costs, the total adjusted cost per 30 hospital days was calculated for each patient and used as the primary HCU outcome. HCU outcomes were analyzed for the alloHCT year, day 0 to day +365. Results: CRF data for 161 patients showed an overall survival at 2 years of 90% (95% confidence intervals [CI] 85-95%): 96% (95% CI 89-100%) for related and unrelated cord blood transplant (CBT), 94% (95% CI 86-98%) matched siblings (MSD), and 74% (95% CI 54-90%) matched unrelated donors (MUD, p=0.002). All deaths occurred among children with pre-alloHCT complications of SCD, and deaths were due to organ failure (37.5%), infections (25%), GVHD (6.25%). Risk of death was significantly higher for children ≥10 years old (HR 21, p=0.003) and MUD compared to MSD (HR 5.88, p=0.005) but lower with cyclosporine A (CSA) GVHD prophylaxis versus FK506 (HR 0.33, p=0.031). 75% of deaths occurred before day +42. Cumulative acute GVHD incidence at day 100 was 14% (95% CI 9-20%)and was associated with age ≥10yrs (HR 2.63, p=0.035). Chronic GVHD incidence was 31% (95% CI 23-38%) at 2yrs, and factors associated were age ≥10yrs (HR 1.92, p=0.034), MUD vs MSD (HR 2.53, p=0.017), and CSA vs FK506 prophylaxis (HR 0.48, p=0.018). Chronic GVHD risk increased significantly after 2006 (HR 2.81, p=0.018). The 2yr GREFS was 64% (95% CI 56-71%). Age ≥10yrs (HR 2.2, p=0.005), MUD (vs MSD, HR 3.00, p=0.002) and CSA prophylaxis (vs FK506, HR 0.49, p=0.011) were significantly associated with this outcome. Among the 175 patients with combined TED and PHIS data, the median total adjusted cost was $117,393 per 30 hospital days per patient (range: $36,244-$515,640) during the alloHCT year with a median of 53 hospital days per patient (range: 16-304). Age ≥10yrs and HCU were not significantly associated (p=0.775). MSD had the lowest HCU compared to CBT and unrelated transplants (p<0.001). CBT and peripheral blood stem cells were associated with higher HCU compared to bone marrow (p=0.004). Increased HCU was associated with prior stroke (p=0.0004) and pain crises (p=0.0094) but not acute chest syndrome (p=0.2913). Overall SCD complication and severity indices correlated with increased HCU (p=0.052, p=0.0219, respectively). Conclusions: AlloHCT outcomes in children with SCD were linked to age and donor type suggesting that early alloHCT before age 10 years is preferred. Specifically, SCD severity and MUD alloHCT are associated with poorer outcomes and increased HCU. This supports the recommendation of early alloHCT, prior to onset of SCD complications, for children with SCD and an available MSD. Donor source and type had a significant impact on both outcomes and HCU. CBT outcomes were similar to MSD bone marrow; yet CBT had higher HCU suggesting additional analysis is needed to determine if the clinical benefit outweighs the cost. Further analysis is also needed to better understand and mitigate risk factors associated with poor outcomes and increased HCU following MUD alloHCT. Disclosures Arnold: Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program: Other: award. Hahn:NIH/NHLBI: Research Funding; Novartis: Equity Ownership.

BACKGROUND: Angioimmunoblastic T cell lymphoma (AITL) has a unique histological phenotype with a relatively small number of malignant T-cells and an extensive infiltrate of normal cells including T-cells, B-cells, NK cells and FDCs. The malignant cell has a T follicular helper (Tfh) cell phenotype with increased expression of immune checkpoint molecules including PD-1 and ICOS. With the routine use of antibodies targeting immune checkpoint molecules, clinical results in limited numbers of AITL patients have thus far been mixed with some responding patients but also some who rapidly progress. Because both malignant T-cells and normal T-cells in AITL may be PD-1 positive, we conducted a study to compare the phenotype of normal T-cells and malignant T-cells within the tumor microenvironment. We also evaluated whether soluble immune checkpoint molecules in the peripheral blood differed between AITLs, controls, and other PTCL subgroups. METHODS: We designed a novel CyTOF antibody (Ab) panel comprised of 37 markers to identify and characterize cells of T, B, NK, macrophage and FDC lineages within a cohort of biopsy specimens from 6 AITL patients compared to 6 normal controls (2 LN, 4 tonsil). Soluble immune receptors and ligands were then measured by multiplex ELISA on peripheral blood from 8 AITLs, 5 controls, and 32 additional samples from PTCL subtypes including PTCL-NOS, ALCL and CTCL. RESULTS: Malignant T-cells in AITL specimens could clearly be identified by viSNE mapping based on CyTOF expression of CD4, CD5, BCL6, CD10 (variable), CXCR5 (variable), PD-1 and ICOS. Aberrant loss of CD3 and CD7 on malignant T-cells was commonly seen. Expression of other immune checkpoint molecules was assessed. Malignant cells expressed high levels of TIGIT and moderate levels of CD27, but malignant T-cell populations were negative for expression of TIM3, LAG3, and CTLA-4. A substantial proportion of normal T-cells also expressed immune checkpoint molecules including PD-1 and CD27, and a subset of these cells also expressed TIGIT and ICOS. A small minority of normal T-cells expressed TIM3, LAG3, and CTLA-4. As others have described, the normal Tfh cell population had an immunophenotype that was otherwise relatively similar to the malignant population, but distinguishable via viSNE mapping with our CyTOF Ab panel. Expression of PD-L1 could be detected on NK-cells, macrophages, and a few select populations of normal T cells, but not on B-cells or FDCs. Malignant T-cells did not express PD-L1. Due to the potential importance of immune checkpoint molecules in this disease, we then measured soluble checkpoint receptors and ligands in the serum. Soluble PD-1 was significantly increased in the peripheral blood of AITL when compared to normal controls (average 2637 pg/mL (SE = 512.1) in AITL vs 57.87 (SE = 16.88) in controls). Similarly, soluble PD-L1 was significantly increased in AITL compared to normal controls (13.8 (SE = 10.5) in AITL vs 0.94 (SE = 0.25) in controls). CONCLUSIONS: Malignant T-cells in AITL have a unique phenotype which was able to be reliably identified through use of viSNE mapping with our CyTOF Ab panel. Furthermore, malignant T-cells were found to consistently express additional immune regulatory molecules beyond PD-1 and ICOS, including TIGIT and CD27. However, a substantial subset of normal T-cells have a very similar phenotype suggesting that activation of T-cells in this disease will likely stimulate both normal and malignant T-cells. This may explain the rapid disease progression seen in a subset of AITL patients treated with PD-1 blockade. Furthermore, soluble PD-1 is significantly increased in the serum of AITL patients and may explain the overall lack of clinical efficacy of anti-PD-1 antibodies in treating AITL. Disclosures Cerhan: NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Ansell:LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; LAM Therapeutics: Research Funding.

Introduction: Emerging evidence supports that cytogenetic abnormalities (CAs) drive myelomagenesis and heterogeneity (e.g., clinical presentation, response to therapy, and prognosis) of multiple myeloma (MM). Diversity of CAs, including primary (IgH translocations and trisomies) and secondary CAs (copy number abnormalities) argues that MM is not a "single disease". Thus, identification of CAs at diagnosis is essential for risk stratification, guiding treatment, and prognostic estimation in daily practice. However, although frequency, configuration, and significance of CAs have been well documented in the Western countries, this information is lacking in the Asian population. To this end, a multi-center retrospective analysis was carried out to examine epidemiology and prognostic significance of CAs alone or in combination in a cohort of Chinese patients with newly-diagnosed MM (NDMM). Materials and Methods: A total of 1015 NDMM patients who had the baseline information of CAs detected by FISH at four institutes nationwide were included. According to the IMWG consensus updated in 2016, 1q gain, del(17p), t[4;14], and t[14;16] were defined as high-risk CAs (HRCAs), while another HRCA t[14;20] was not tested routinely in a majority of these patients. In addition, del(1p) and del(13q14) were considered as an adverse CA. According to the mSMART3.0 proposed by Mayo Clinic in 2018, double-hit (DHMM) and triple-hit MM (THMM) were defined as co-occurrence of 2 or >= 3 HRCAs, respectively. The Kaplan-Meier approach was used to estimate progression-free survival (PFS) and overall survival (OS). Results: In this cohort, the median age of 1015 patients was 61 years; 63.5% were male. The type of IgG, light chain, IgA, IgD, non/oligosecretory, IgM, or IgE accounted for 42.9%, 26.2%, 24.5%, 3.4%, 2.5%, 0.4%, and 0.1%, respectively. Del(13q) (46.4%) and 1q gain (46.1%; 3 copies = 73.8%, >= 4 copies = 26.2%) represented the most common CAs, followed by t(4;14) (14.0%), t(11;14) (11.8%), del(1p) (11.5%), del(17p) (9.9%; 20-50% cells = 35.6%, > 50% cells = 64.4%), and t(14;16) (5.1%). While none of these CAs was detected in 23.8% of cases, the frequency of patients who carried 1 - 5 CAs was 31.9%, 28.0%, 13.4%, 2.0%, and 0.9%, respectively. In the 1q+ cases, 36.4% patients carried second CA(s), including del(13q) (61.1%), t(4;14) (20.3%), del(1p) (14.8%), del(17p) (10.7%), t(11;14) (10.4%), and t(14;16) (8.1%). In the del(17p) cases, 57.5% patients had additional CA(s), including del(13q) (75.2%), 1q gain (49.5%), del(1p) (21.6%), t(4;14) (19.6%), t(14;16) (8.7%), and t(11;14) (2.2%). In the cases bearing IgH translocations, 26.0% patients also carried other CA(s), including del(13q) and 1q gain (61.9% for each), and del(17p) (9.3%). In the cases harboring HRCAs, the percentage of patients who carried 1 - 4 HRCAs was 70.2%, 24.8%, 3.7%, and 1.1%, respectively. Overall, 14.3% and 2.9% patients had DHMM or THMM, of whom 65.0%, 18.0%, 12.0%, and 5.0% had 2 - 5 HRCAs, respectively. While there was no significant difference in PFS between the cases carrying 1 and 2 CAs (P = 0.209), the patients who had 3 or more CAs displayed a sharp reduction in median PFS (P = 0.022 and P = 0.003 for 3 vs 1 or 2 CAs). Although multiple CAs was associated with shorter median OS, no statistical significance was observed for each comparison (P > 0.05). However, patients who carried >= 2 HRCAs had significantly shorter median PFS (12.1 months; P = 0.0004) and OS (29.3 months; P = 0.027) than those who had one single HRCA (32.2 and 65.6 months for median PFS and OS). Conclusion: In comparison with the Western countries, the incidence of secondary HRCAs (e.g., 1q gain and del(17p)) is relatively higher in Chinese patients at diagnosis, while the standard-risk CA such as t(11;14) is clearly less frequent. The proportion of Chinese patients who carry multiple CAs (up to 5) or HRCAs appear to be greater as well. In this context, patients carrying two or more HRCAs, so called DHMM or THMM, exhibit significantly worse outcome than those carrying only one HRCA. Together, this study builds up an up-to-date profile of CAs for Chinese patients, which might lay a foundation for revising the criteria for risk stratification and the guideline for treatment that is more feasible and practicable in China. It also provides the information about frequency and configuration of MM-driven CAs, which might be more relevant to the Asian population. Disclosures Kumar: Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.