Abstract: Breast cancer is now the most common malignant tumor worldwide. About one-fourth of female cancer patients all over the world suffer from breast cancer. And about one in six female cancer deaths worldwide is caused by breast cancer. In terms of absolute numbers of cases and deaths, China ranks first in the world. The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China. Methods The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to classify evidence and consensus. Results The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer, breast cancer screening, breast cancer diagnosis, early breast cancer treatment, advanced breast cancer treatment, follow-up, rehabilitation, and traditional Chinese medicine treatment of breast cancer patients. Conclusion We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Abstract: The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined. Methods The Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome (CCC–ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan–Meier curves, and subgroup analyses were conducted. Results The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk of major adverse cardiac events (MACE) (0.51% vs. 1.43%, P  = 0.007), and all-cause death (0.36% vs. 0.99%, P  = 0.028), the risks of myocardial infarction and major bleeding were not significantly different between patients with and without reloading. In survival analysis, a lower cumulative risk of MACE could be identified (Log-rank test, P  = 0.007) in reloading group. In the unadjusted Cox model, reloading P2Y12 receptor inhibitors was associated with a decreased risk of MACE [HR, 0.35; 95% CI 0.16–0.78; ( P  = 0.010)] and all-cause death [HR, 0.37; 95% CI 0.14–0.94; ( P  = 0.036)]. Reloading of P2Y12 receptor inhibitors was associated with a decreased risk of MACE in most of the subgroups. Conclusions In NSTEACS patients already taking P2Y12 receptor inhibitors, we observed a decreased risk of in-hospital MACEs and all-cause mortality and did not observe an increased risk of major bleeding, with reloading. The differential profile in the two groups might influence this association and further studies are warranted. Clinical trial registration : https://www.clinicaltrials.gov (Unique identifier: NCT02306616, date of first registration: 03/12/2014)

Abstract: Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. In phase 3 clinical studies, the addition of daratumumab to standard-of-care regimens consistently demonstrated a significant progression-free survival (PFS) benefit and improved depth of response, including minimal residual disease-negativity, in patients (pts) with newly diagnosed MM or RRMM. In the primary analysis of the phase 3 CASTOR study (median follow-up: 7.4 mo), D-Vd reduced the risk of disease progression or death by 61% (median PFS, not reached [NR] vs 7.2 mo; hazard ratio [HR] , 0.39; 95% confidence interval [CI], 0.28-0.53; P & lt;0.001) and induced higher rates of deeper responses vs Vd in global pts with RRMM who received ≥1 prior line of therapy (Palumbo A, et al. N Engl J Med. 2016;375[8]:754-766). More recently, a similar clinical benefit of D-Vd was demonstrated in Chinese pts with RRMM who received ≥1 prior line of therapy in the phase 3 LEPUS study (Huang X, et al. EHA 2020. EP988). At a pre-specified interim analysis (median follow-up: 8.2 mo), D-Vd reduced the risk of disease progression or death by 72% (median PFS, NR vs 6.3 mo; HR, 0.28; 95% CI, 0.17-0.47; P & lt;0.00001) and induced higher rates of deeper responses vs Vd. Here, we report the results of a pooled subgroups analysis, including Chinese pts in LEPUS and global pts in CASTOR, examining the efficacy of D-Vd vs Vd based on age, cytogenetic risk status, and renal function, at a median follow-up of 7.5 months. Methods: Eligible pts in LEPUS and CASTOR received ≥1 prior line of therapy and were randomized 2:1 in LEPUS and 1:1 in CASTOR to 8, 21-day cycles of V (1.3 mg/m2 SC) on Days 1, 4, 8, and 11, and d (20 mg, PO or IV) on Days 1, 2, 4, 5, 8, 9, 11, and 12 ± D (16 mg/kg IV) given QW for Cycles 1-3, Q3W for Cycles 4-8, and Q4W thereafter. The primary endpoint for both studies was PFS. Results: A total of 211 (D-Vd, n=141; Vd, n=70) pts in LEPUS and 498 (D-Vd, n=251; Vd, n=247) pts in CASTOR were randomized. The median (range) age was 61 (28-82) years for Chinese and 64 (30-88) years for global pts. In general, baseline characteristics were similar between Chinese and global pts and balanced between treatment arms, with the exception of median body weight (LEPUS: 67 kg; CASTOR: 76 kg). Chinese and global pts both received a median of 2 prior lines of therapy; 79% and 66% received prior V, 27% and 28% were refractory to lenalidomide, and 64% and 32% were refractory to their last prior line of therapy, respectively. After a median follow up of 8.2 months in LEPUS and 7.4 months in CASTOR, a consistent PFS benefit of D-Vd vs Vd was demonstrated in the pooled analysis set across age ( & lt;65, 65-74, and ≥75 years), cytogenetic risk status (standard risk and high risk), and renal function (creatinine clearance ≤60 mL/min and & gt;60 mL/min) subgroups (Table 1). Median time to progression was also consistently prolonged with D-Vd vs Vd across pooled pt subgroups. Among response evaluable pts, D-Vd improved overall response rate, rate of very good partial response or better, and rate of complete response or better (Table 2) and prolonged median duration of response vs Vd in all pt subgroups. Additional data, including PFS2, from the pooled subgroups analysis will be presented at the meeting. The safety profile of D-Vd was generally consistent across pts in LEPUS and CASTOR. Grade 3/4 treatment-emergent adverse events (TEAEs; D-Vd/Vd) occurring at a ≥5% frequency with D-Vd vs Vd in both Chinese and global pts included thrombocytopenia (51%/37%; 45%/33%), lymphopenia (44%/29%; 10%/3%), neutropenia (16%/6%; 13%/4%), and hypertension (12%/3%; 7%/1%). 49%/38% of Chinese and 42%/34% of global pts had ≥1 serious TEAEs. TEAEs leading to treatment discontinuation occurred in 4%/3% of Chinese and 7%/9% of global pts, and TEAEs leading to death occurred in 4%/10% of Chinese and 5%/6% of global pts. Rates of infusion-related reactions (IRRs) were similar for D-Vd across studies (LEPUS: 38%; CASTOR: 45%); most occurred during the first infusion and the majority were grade 1/2. Conclusions: D-Vd demonstrated a clinical benefit, including significantly improved PFS, in pooled Chinese and global pts with RRMM who received ≥1 prior line of therapy, regardless of age, cytogenetic risk status, or renal function. The safety profile of D-Vd was consistent across all pts, and no new safety concerns were identified. These results support the use of D-Vd in Chinese pts with RRMM. Disclosures Jin: The First Affiliated Hospital of Zhejiang University: Current Employment. Spencer:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Cilag GmbH: Consultancy, Honoraria, Research Funding, Speakers Bureau. Weisel:Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; GlaxoSmithKline: Honoraria. Mateos:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Nooka:Adaptive Technologies: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Oncopeptides: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding. Qi:Janssen: Current Employment, Current equity holder in publicly-traded company; Johnson and Johnson: Current equity holder in publicly-traded company. Sun:Janssen: Current Employment, Current equity holder in publicly-traded company. Gai:Janssen: Current Employment, Current equity holder in publicly-traded company. Liu:Janssen: Current Employment, Current equity holder in publicly-traded company. Yang:Janssen: Current Employment, Current equity holder in publicly-traded company.

Abstract: To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis. Methods Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the two drugs and finerenone indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). Results 18 RCTs involving 51,496 patients were included. Finerenone reduced the risk of major adverse cardiovascular events (MACE), renal outcome and hospitalization for heart failure (HHF) (RR [95% CI]; 0.88 [0.80–0.97] , 0.86 [0.79–0.93], 0.79 [0.67,0.92] , respectively). SGLT-2i were associated with reduced risks of MACE (RR [95% CI]; 0.84 [0.78–0.90] ), renal outcome (RR [95% CI]; 0.67 [0.60–0.74] , HHF (RR [95% CI]; 0.60 [0.53–0.68] ), all-cause death (ACD) (RR [95% CI]; 0.89 [0.81–0.91] ) and cardiovascular death (CVD) (RR [95% CI]; 0.86 [0.77–0.96] ) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95% CI]; 0.86 [0.78–0.94] ). SGLT2i had significant effect in comparison to finerenone (finerenone vs SGLT2i: RR [95% CI]; 1.29 [1.13–1.47] , 1.31 [1.07–1.61], respectively) and GLP-1 RA (GLP-1 RA vs SGLT2i: RR [95% CI] ; 1.36 [1.16–1.59], 1.49 [1.18–1.89] , respectively) in renal outcome and HHF. Conclusions In patients with T2DM and CKD, SGLT2i, GLP-1 RA and finerenone were comparable in MACE, ACD and CVD. SGLT2i significantly decreased the risk of renal events and HHF compared with finerenone and GLP-1 RA. Among GLP-1 RA, GLP-1 analogues showed significant effect in reducing cardiovascular events compared with exendin-4 analogues.

Abstract: e20002 Background: ATG-010 is a novel, oral selective inhibitor of nuclear export inhibiting exportin 1. In preclinical and clinical studies, ATG-010 has demonstrated activity against multiple myeloma (MM). ATG-010 (80 mg biweekly) plus dexamethasone (20 mg biweekly) (Sd) was approved by US FDA for treatment of patients (pts) with penta-refractory MM in 2019 based on the STORM study. MARCH is a single arm, Phase 2 study to assess efficacy and safety of Sd in Chinese pts with RRMM. Methods: Enrolled pts have been previously treated with and refractory to PI, IMiD, and the last line of therapy. Sd is administered in 4-week cycles. Primary endpoint is overall response rate (ORR) per independent review committee. The total planned enrollment of 82 pts provides ̃80% power to test against H 0 of 15% ORR at one-sided α of 0.025. This abstract provides data from a planned analysis of the first 60 treated pts. Results: As of 13 Oct 2020, 18 (30%) of the 60 pts were on treatment. Median follow-up was 9.5 months (mo) (range: 1.9-12.8). Median age was 61 years (range 43-82; 42% 〉 65). Pts had received a median of 5 (range 1-16) prior MM regimens, with following baseline risk factors: 72% R-ISS II/III, 70% cytogenetic abnormalities, 22% del (17p13),20% renal impairment, 15% prior CAR-T therapy, and 25% pre-treated with daratumumab (considered ‘triple-class exposed’). ORR was 26.7% (95% CI: 16.1, 39.7). Median DOR was 4.6 mo (95% CI: 1.42, NE). Median PFS was 3.7 mo (95% CI: 1.92, 4.66). Median OS was not reached; 9-mo OS rate was 68.5%. ORR was 33.3% in triple-class-exposed pts, and 44.4% in pts with prior CAR-T. ORR was generally consistent across subgroups. Common TEAEs of any grade included: thrombocytopenia (87%), nausea (87%), leukopenia (85%), anemia (85%), lymphopenia (78%), neutropenia (73%), weight loss (72%), hyponatremia (65%), decreased appetite (63%), asthenia (62%)/fatigue (17%), hyperglycemia (53%), vomiting (52%), hypocalcemia (38%), hypokalemia (30%), diarrhea (30%), pneumonia (27%). Common TEAEs of Grade ≥ 3 included: anemia (60%), thrombocytopenia (55%), leukopenia (42%), lymphopenia (42%), neutropenia (38%), hyponatremia (28%), and pneumonia (23%). Thirty pts (50%) had TESAEs, including ( 〉 3%): thrombocytopenia (15%), pneumonia (15%), anemia (6.7%), hyponatremia (3.3%). Eight pts (13.3%) had TEAEs leading to treatment discontinuation, including ( 〉 2%): thrombocytopenia (5%) and pneumonia (3%). Three fatal TEAEs were pneumonia, intracranial hemorrhage and sudden death (1 each). Conclusions: In Chinese RRMM pts refractory to both IMiD and PI, with a highly unmet medical need, MARCH confirms the efficacy of Sd as a promising new oral therapeutic option with a manageable safety profile, which is consistent with STORM. Clinical trial information: NCT03944057.

Abstract: The bladder patch constructed with the bladder acellular matrix (BAM) and adipose-derived stem cells (ASCs) was incubated with the omentum for bladder reconstruction in a rat model of bladder augmentation cystoplasty. A self-designed perfusion system and five different decellularization protocols were used to prepare the BAM. Finally, an optimal protocol (group C) was screened out by comparing the cell nucleus residue, collagen structure preservation and biologically active components retention of the prepared BAM. ASCs-seeded (BAM-ASCs group) and unseeded BAM (BAM group) were incubated with the omentum for 7 days to promote neovascularization and then perform bladder reconstruction. Hematoxylin and eosin and Masson’s trichrome staining indicated that the bladder patches in the BAM-ASCs group could better regenerate the bladder wall structure compared to the BAM group. Moreover, immunofluorescence analyses demonstrated that the ASCs could promote the regeneration of smooth muscle, neurons and blood vessels, and the physiological function (maximal bladder capacity, max pressure prior to voiding and bladder compliance) restoration in the BAM-ASCs group. The results demonstrated that the self-designed perfusion system could quickly and efficiently prepare the whole bladder scaffold and confirmed that the prepared BAM could be used as the scaffold material for functional bladder tissue engineering applications.