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A workflow for the numerical prediction of in-flight ice accretion on 3D structures is presented. The method is based on the predictor–corrector approach, which has been so far mainly developed in 2D codes and assessed in straight-wing test cases. The adaptations made for the 3D implementation are thus described. Among other developments, a remeshing technique based on the Dragon method is presented. The new methods are verified against reference numerical data. The whole workflow is validated using several test cases for which experimental measurements of ice shapes are available. Both straight and swept wings are therefore investigated. The numerical results are encouraging for low-sweep angles. Some recommendations are made for improving the results, including the need for new ice-density models. The predictor–corrector method is poorly adapted for cases exhibiting large scallop-like structures, which tends to be reinforced by high sweep angles. In this article, the test cases with highest sweep angle are effectively calculated less accurately. Costly multi-step ice-accretion simulations should be preferred for such conditions, unless a special ice bulk density model is developed.

Introduction:Novel T-cell redirecting therapies (TCR), including chimeric antigen receptor T-cell therapy (CAR-T) and bispecific antibodies (BsAbs), are important new treatment options for patients (pts) with relapsed/refractory multiple myeloma (RRMM) but result in a new unmet need for pts who relapse following these therapies. Talquetamab is the most advanced BsAb therapy targeting G protein-coupled receptor family C group 5 member D (GPRC5D), a novel antigen that is overexpressed on malignant plasma cells but is expressed at low levels on B cells and bone marrow progenitors. Previous results from the phase 1/2 MonumenTAL-1 study (NCT03399799/NCT04634552) demonstrated deep and durable responses with talquetamab in pts with RRMM, with an overall response rate (ORR) of >71% in 288 pts naive to TCR and 65% in 51 pts with prior TCR. Here, we present updated results in pts with prior TCR, including an additional 19 pts enrolled since the prior analysis.

Introduction:Patients (pts) with advanced and heavily pretreated relapsed/refractory multiple myeloma (RRMM) have worse health-related quality of life (HRQoL) than those at earlier stages of the disease and have limited treatment options available to enable improvement in HRQoL, particularly those who are triple-class exposed. Talquetamab (tal), a novel GPRC5D×CD3 bispecific antibody, has shown deep and durable responses in the MonumenTAL-1 study (NCT03399799/NCT04634552) in pts with RRMM. Here, we report patient-reported outcomes (PROs) from the MonumenTAL-1 study, focusing on data through cycle 21 from the tal 0.4 mg/kg weekly (QW) dosing cohort (initial results presented at ASH 2022) and new data through cycle 15 from the tal 0.8 mg/kg every other week (Q2W) dosing cohort.

Introduction:Talquetamab (tal), a novel GPRC5D×CD3 bispecific antibody (BsAb), has shown deep and durable responses with overall response rates (ORRs) >71%, including in high-risk populations, and a clinically manageable safety profile in patients (pts) with relapsed/refractory multiple myeloma (MM) in the MonumenTAL-1 study (NCT03399799/NCT04634552). To better understand mechanisms of resistance and relapse in pts treated with tal, baseline and longitudinal GPRC5D expression and immune profiles were assessed in pts treated with the 0.4 mg/kg weekly (QW) recommended phase 2 dose, including a separate cohort of pts who received prior T-cell redirection therapy (prior TCR; chimeric antigen receptor [CAR]-T cell and BsAb therapies).

Introduction:Talquetamab (tal) is an off-the-shelf, T-cell redirecting bispecific antibody (BsAb) targeting G protein-coupled receptor family C group 5 member D. Results from the phase 1/2 MonumenTAL-1 (NCT03399799/NCT04634552) trial showed overall response rates (ORRs) of >71%, which were durable, and a manageable safety profile with the recommended phase 2 doses (RP2Ds) of subcutaneous (SC) tal, 0.4 mg/kg weekly (QW) or 0.8 mg/kg every other week (Q2W), in patients (pts) with relapsed/refractory multiple myeloma. Data with tal also demonstrated preservation of B cells throughout treatment, contributing to relatively few severe infections. To date, there is a paucity of data describing pt outcomes after T-cell redirection therapies. Here, we report outcomes for pts who received subsequent antimyeloma therapies (SATs) after discontinuing tal in MonumenTAL-1, including pts who went on to receive subsequent T-cell redirection therapies.

Introduction:Talquetamab (tal) is an off-the-shelf, T-cell redirecting bispecific antibody targeting G protein-coupled receptor family C group 5 member D (GPRC5D) and CD3. Results from the phase 1/2 MonumenTAL-1 (NCT03399799/NCT04634552) trial showed overall response rates (ORRs) of >71% and a manageable safety profile with the recommended phase 2 doses (RP2Ds) of subcutaneous tal (0.4 mg/kg weekly [QW] or 0.8 mg/kg every other week [Q2W]) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). The impact of reducing dose intensity with bispecifics on safety and efficacy is an area of clinical interest. We report safety and efficacy in pts from MonumenTAL-1 who switched to less frequent or reduced dosing with tal.

Heat is a major problem in electronics. A cold plate which transfers heat to an absorbing media in a forced flow can be used to cool modern integrated circuits. Coldplate is a new software for automating the process for cold plates. The software is applicable for both isothermal and nonisothermal analyses. Coldplate is capable of finding results of several trade-offs such as fin-to-fin spacing, fin height and material and flow rates., Some of the biggest problems in electronics today concern getting rid of heat. High-speed Pentium chips, for example, are notorious space heaters. Cooling modern ICs such as these frequently involves [...]

Despite an almost 80 overall survival rate in pediatric T-cell acute lymphoblastic leukemia (T-ALL), there is a subset of patients who are refractory to standard chemotherapy regimens and could benefit from novel treatment approaches. Over a 2-year period, we treated 5 pediatric patients with refractory T-ALL, aged 3 to 15 years, with high-dose cyclophosphamide (CY) at a dose of 2100 mgm2for 2 consecutive days either alone (n=1) or in combination with other chemotherapy agents (n=4). Four of these 5 patients had a 1.5 log decrease in disease burden. Three of the 5 patients had no evidence of minimal residual disease (MRD) after high-dose CY. One patient developed transient grade 4 transaminitis and 1 patient developed grade 3 typhlitis. All 5 patients ultimately proceeded to hematopoietic stem cell transplant when MRD levels were <0.01. Pediatric T-ALL patients with persistent MRD after treatment with conventional chemotherapy may respond to CY at escalated dosing.

The VC2 vorticity confinement technique introduced by Steinhoff for vortex dominated flows is presented. After a brief description of the formulation and of its theoretical developments, the method is applied to the simulation of helicopter rotor wakes, focusing on two configurations: the rotor in hover, for which the flow field is mainly driven by the wake characteristics, and the rotor in low-speed descent flight where BVI noise is created. The results obtained show the efficiency of the approach, which provides wake predictions of the same or even better quality as higher-order methods.

Introduction: Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, is approved in combination with standard-of-care regimens for the treatment of newly diagnosed multiple myeloma (NDMM) and RRMM. When combined with standard of care regimens across four phase 3 studies, daratumumab demonstrated ≥44% reductions in the risk of progression or death, nearly doubled complete response (CR) or better rates, and tripled minimal residual disease (MRD)-negative rates at the 10-5sensitivity threshold in pts with RRMM or NDMM (Palumbo A, et al. N Engl J Med2016. 375[8]:754-766; Dimopoulos MA, et al. N Engl J Med2016. 375[14]:1319-1331; Mateos MV, et al. N Engl J Med2018. 378[6]:518-528; Facon T, et al. N Engl J Med2019. 380[22]2104-2015). In the phase 3 POLLUX study (median follow-up 44.3 months), D-Rd reduced the risk of disease progression or death by 56% and significantly increased the overall response rate (ORR) versus Rd alone (93% vs 76%; P<0.0001) in patients (pts) with RRMM. Here, we present updated efficacy and safety analyses of POLLUX after >4 years of median follow-up.

Bahlis: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Zonder:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Intellia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Caelum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wroblewski:Janssen: Employment, Equity Ownership. Qi:Janssen: Employment. Renaud:Janssen: Employment, Equity Ownership. Jackson:Janssen: Employment, Equity Ownership. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees.This presentation/paper includes information/discussion of a subcutaneous formulation of daratumumab, which is currently under investigation in several clinical trials, but has not yet been approved. The intravenous formulation of daratumumab is approved as monotherapy and in combination with standard-of-care regimens for the treatment of MM.

Kobos: Janssen: Employment. He:Foundation Medicine, Inc: Employment, Equity Ownership. Roshal:BD Biosciences: Consultancy. Zhong:foundation medicine: Employment. Balasubramanian:Foundation Medicine, Inc: Employment, Equity Ownership. Nahas:Foundation medicine: Employment. Vergilio:Foundation Medicine: Employment. Ross:Foundation Medicine, Inc: Employment. Stephens:Foundation Medicine, Inc: Employment, Equity Ownership. Mughal:Foundation Medicine: Employment, Equity Ownership. Miller:Foundation Medicine: Employment, Equity Ownership. Levine:Qiagen: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy.

Off Label Use: CAR T cells for relapsed B-ALL. Riviere:Juno Therapeutics: Consultancy, Scientific co-founder and Stock holder Other. Boulad:Genzyme Sanofi: Trials partially funded by Genzyme Sanofi Other. Sadelain:Juno Therapeutics: Consultancy, Scientific co-founder and Stock holder Other. Brentjens:Juno Therapeutics: Consultancy, Scientific co-founder and Stock holder Other.

Boulad: Genzyme Sanofi: Trials partially funded by Genzyme Sanofi Other.

Sasu: Amgen Inc.: Employment. Cooke:Amgen Inc.: Employment. Rivella:Novartis: Consultancy; Bayer: Consultancy; Isis: Consultancy, Research Funding; Merganser: Equity Ownership, Research Funding; Biomarin: Consultancy; Alexion: Consultancy; Imago: Consultancy.

Outcomes for children with relapsed/refractory acute leukemia remain dismal. Clofarabine has been approved for the treatment of relapsed acute lymphoblastic leukemia (ALL). However activity in pediatric acute myelogenous leukemia (AML), and optimal combination chemotherapy regimens have yet to be established. We previously reported a 36% complete remission (CR) rate with gemcitabine in combination with topotecan, vinorelbine, and thiotepa (TVTG) in relapsed/refractory pediatric acute leukemias. In an effort to improve on the outcomes of TVTG, we substituted clofarabine for the gemcitabine to create the TVTC protocol.Following completion of a phase I study, a phase II trial of TVTC was conducted. Patients with relapsed/refractory ALL or AML were eligible. Patients were treated at the maximum tolerated dose (MTD) as determined from the preceding phase I study: clofarabine 40mg/m2/day IV × 5 days, topotecan 1mg/m2/day IV continuous infusion × 5 days, vinorelbine 20mg/m2/week IV × 3, and thiotepa 15mg/m2/day IV × 1 day. The primary endpoint was overall response rate (ORR), defined as CR or CR without platelet recovery (CRp). 17 patients were enrolled. The median age was 10 years (8 months – 24 years). 12 patients had AML, 4 had pre-B ALL, and 1 had biphenotypic leukemia. 13 patients had relapsed disease, and 4 had refractory disease. 2 of the 17 patients were inevaluable for response; one patient was enrolled with minimal residual disease positivity of leukemia, and one patient is currently undergoing therapy.Of the 15 patients evaluable for response, the ORR was 73% (10 CR, 1 CRp). Among the 11 responders, 10 (91%) proceeded to stem cell transplantation. Of the 4 non-responders, 2 patients had no detectable leukemia in their follow-up marrow samples, but failed to have count recovery. The other 2 patients were refractory to therapy. 16 of the 17 patients were evaluable for overall survival (OS), as one patient is currently undergoing therapy. The OS of the 16 evaluable patients is 53%, with a median OS time of 16.2 months (1.5 – 57.7 months). The most common grade 3 or higher toxicities included febrile neutropenia (69%), transient transaminase elevation (50%), and catheter-related infection (44%). One of the patients died from cardiac arrest 45 days after beginning TVTC. There were no cases of VOD.TVTC demonstrates significant activity in patients with relapsed/refractory acute leukemia. Infectious complications occurred at similar rates to previously reported clofarabine combination studies. The activity seen in relapsed/refractory AML patients was very encouraging, with 8 of 11 (73%) evaluable patients achieving a CR/CRp. Given the high response and stem cell transplantation rates in relapsed AML patients on this study, patients with high risk de novo AML may benefit from incorporation of TVTC therapy into their treatment regimens. This regimen warrants further exploration in a larger cohort of relapsed leukemia patients.Off Label Use: Use of Clofarabine for patients with AML. Steinherz:Genzyme: Research Funding.

Cooke: Amgen: Employment. Sasu:Amgen: Employment.

No relevant conflicts of interest to declare.