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Long-duration spaceflights reportedly induce immune dysregulation, which is considered a risk to astronaut safety and mission success. Recent studies have examined the impact of spaceflight on markers of adaptive and innate immunity, but no study, to date, has comprehensively evaluated humoral immunity and serological markers of B cell function. The aim of this study was to characterize changes in B cell numbers and phenotypes, along with plasma Igs and polyclonal free light chains (FLCs)—near-“real-time” biomarkers of Ig synthesis—in response to an ~6-mo mission to the International Space Station (ISS). Whole-blood samples were collected before flight, during flight (“Early flight,” “Mid-flight,” and “Late flight”), immediately upon return, and during a recovery period (R + 18, R + 30/R + 33, and R + 60/R + 66) from 23 ISS crew members. B Cell counts and phenotypes were measured throughout the duration of the mission, along with total plasma Ig and FLC levels. There was no effect of spaceflight on the number and proportion of the different B cell subsets. There was no difference in kappa FLC between preflight samples and either in-flight or recovery samples ( P > 0.05), and only a marginal reduction was observed in lambda FLC levels upon return to Earth ( P < 0.05). Furthermore, IgG and IgM remained unchanged during and after spaceflight compared with preflight values ( P > 0.05). Of note, plasma IgA concentrations were elevated in-flight compared with baseline and recovery values ( P < 0.05). These results indicate that B cell homeostasis is maintained during long-duration spaceflight, advocating for potential in-flight vaccination as viable countermeasures against viral reactivation during exploration-class missions.

Background Limited data exist on the safety of using anti–human epidermal growth factor receptor 2 (HER2) targeted agents during pregnancy. To date, only retrospective studies have assessed the prognosis of patients with a pregnancy after prior early breast cancer, with no data in HER2‐positive patients. Methods The Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial and the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial were randomized phase 3 trials for patients with HER2‐positive early breast cancer. In both trials, pregnancy information was prospectively collected. Pregnancy outcomes were compared between patients unintentionally exposed to trastuzumab and/or lapatinib during gestation (the exposed group) and those who became pregnant after trastuzumab and/or lapatinib completion (the unexposed group). In the ALTTO trial, disease‐free survival (DFS) was compared between pregnant patients and those aged 40 years or younger without a subsequent pregnancy via an extended Cox model with time‐varying covariates to account for a guarantee‐time bias. Results Ninety‐two patients (12 in the exposed group and 80 in the unexposed group) had a pregnancy: 7 in the NeoALTTO trial and 85 in the ALTTO trial. Seven patients (58.3%) in the exposed group and 10 patients (12.5%) in the unexposed group opted for an induced abortion; in the unexposed group, 10 patients (12.5%) had a spontaneous abortion. No pregnancy/delivery complications were reported for the remaining cases, who successfully completed their pregnancy, with the exception of 1 fetus with trisomy 21 (Down syndrome). No significant difference in DFS (adjusted hazard ratio, 1.12; 95% confidence interval, 0.52‐2.42) was observed between young patients with a pregnancy (n = 85) and young patients without a pregnancy (n = 1307). Conclusions For patients with HER2‐positive early breast cancer, having a pregnancy after treatment completion appears to be safe without compromising fetal outcome or maternal prognosis.

Problem Case-based learning is an established means of educating students in law, business, and medicine; however, this methodology is not often applied to educating translational biomedical researchers. The application of case-based learning to translational biomedical research education allows scholars to actively engage with real-world material and apply their newfound knowledge as it is acquired. Approach Through the Mayo Clinic Center for Clinical and Translational Science (CCaTS), three courses were delivered in 2009–2017 which emphasized case-based learning in clinical and translational science, entrepreneurship, and individualized medicine. Quantitative measures collected in student course reviews upon course completion were analyzed. Additionally, products arising from each course were identified, including publications and startups pitched. Outcomes Analyses demonstrate that case-based learning techniques are well suited to graduate biomedical research education. Furthermore, case studies can be employed throughout the entire clinical and translational spectrum, from basic and preclinical work through to clinical and population-based learning. Next Steps Within CCaTS, next steps include creating case-based courses in regulatory and team science to continue to allow scholars to learn and apply these critical skills to real-world material. The goal is to continue to provide immersive training opportunities in areas of clinical and translational science that cannot be readily learned in a traditional lecture-based class setting.

As new cancer treatment regimens demonstrate increased potential to improve patients’ survival, more focus is directed toward the quality of that extension of life and to obtaining additional information from patients regarding their experience with treatment. The utility of capturing patient-reported treatment-related symptoms to complement traditional clinician-rated symptomatic adverse event reporting is well-documented. The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library aimed at capturing patient-reported symptoms to inform the patient perspective on a treatment’s tolerability. The U.S. Food and Drug Administration has recommended using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in clinical trials. A practical guideline is needed to inform a priori selection of specific Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items for use in any given industry-sponsored oncology clinical trial. Standardizing this selection process will foster systematic and consistent data collection as part of drug development and enhance our knowledge on how to use patient-relevant information as part of a treatment’s risk/benefit assessment. This article presents methods and consensus recommendations for selecting specific Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items to include in early-phase and late-phase oncology clinical trials.

TPS7577 Background: Nivolumab (nivo) is a PD-1 immune checkpoint inhibitor that augments T-cell activation and host anti-tumor responses. PD-1 blockade has shown promise in B- and T-cell non-Hodgkin lymphoma (NHL),1 but many patients (pts) with NHL do not respond or progress after response. Combination therapy using anti-tumor agents with complementary mechanisms of action and low immunosuppressive impact may result in more frequent and durable responses. Brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate that induces cell cycle arrest and apoptosis, with activity in a range of NHL tumors.2,3 Tumor cells undergoing BV-induced apoptosis have shown subsequent immune-mediated anti-tumor cytotoxicity.4 Therefore, nivo and BV may synergize if combined for relapsed/refractory (RR) NHL. Methods: CheckMate 436 (NCT02581631) is a phase 1–2, open-label, international, single-arm study evaluating nivo + BV for CD30-expressing RR NHL (study start: Dec 2015) in pts with RR diffuse large B-cell lymphoma, peripheral T-cell lymphoma (excluding anaplastic large cell lymphoma), and cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome); cohorts with primary mediastinal B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma were made eligible in Sept 2016. Pts with PMBL must be aged ≥15 y (≥18 y for other histologies). All pts must have CD30-expressing disease, defined by CD30 on ≥1% of tumor cells or tumor-infiltrating lymphocytes by immunohistochemistry. In the phase 1 component, 6 pts will receive nivo and BV until disease progression or unacceptable toxicity. In the phase 2 component, ~130 more pts across the 5 histologies will be enrolled and treated at the recommended dose. Primary endpoints: safety, tolerability, and investigator-assessed objective response rate; secondary endpoints: duration of response and complete response (CR), CR rate, and progression-free and overall survival. Accrual is ongoing. References: 1. Lesokhin A et al. JCO 2016;34:2698–704 2. Jacobsen E et al. Blood 2015;125:1394–402 3. Horwitz S et al. Blood 2014;123:3095–100 4. Gardai S et al. Cancer Res 2015;75(15 Suppl):2469 [abstract]. Clinical trial information: NCT02581631.

4519 Background: Tandem HDC with carbo/etoposide (CE) is curative for a portion of relapsed GCT pts. However, outcomes of refractory or high-risk relapsed pts remain poor. We tested a new HDC regimen of GemDMC, based on DNA damage repair inhibition. We combined BEV with HDC given their potential synergy and the high vascularity of GCT metastases. Methods: Eligibility: Intermediate (int)/high-risk (Beyer Model), creatinine ≤1.8 mg/dL and adequate organ function. HDC included BEV (5 mg/kg) preceding GemDMC (HDC #1) and ifosfamide/CE (ICE) (HDC #2). Following accrual of 42 pts, we amended the trial omitting BEV. The trial was powered to distinguish a target 50% 2-yr RFS from an expected 25% in this population. Results: We enrolled 69 male pts in cohorts 1 (BEV, N=42) and 2 (no BEV, N=27) (Table). Pts were heavily pretreated and most had refractory tumors. Main AE: mucositis and renal (4 HDC-related deaths in cohort 1, 1 in cohort 2). Tumor markers normalized in 90% pts with active tumors at HDC. After HDC, 19 pts were in CR and 28 in PRm- (of these, 22 had residual lesions resected with no viable tumor found in 20/22, 2 xRT, 4 monitored). Median f/u = 39 (2-105) mo. The 2-yr RFS rates in cohorts 1 and 2 = 52% and 78%, respectively. Their respective 2-yr OS rates = 55% and 81%. Conclusions: Sequential HDC with GemDMC–ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the anticipated results. Addition of BEV increases toxicity but not tumor control. Clinical trial information: NCT00936936. [Table: see text]