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Targeted busulfan dosing helps limit chemotherapy-related toxicity and optimize disease outcomes in hematopoietic stem cell transplantation (HCT). The objective of this study was to evaluate busulfan exposure from a pharmacokinetic (PK)-guided dosing strategy using a test dose. This retrospective evaluation included adult patients who underwent HCT at our institution with busulfan-based myeloablative (>9 mg/kg) conditioning between January 2014 and October 2015. A weight-based test dose of 0.8 mg/kg was used with PK assessments to predict area under the curve (AUCpred) achieved with weight-based dosing, with a target AUC of 4800 µM*minute (AUCtarget). PK from the test dose was then used to calculate a PK-guided first myeloablative busulfan dose. PK assessments were also done after the first dose to assess if the goal area under the curve (AUC) had been achieved (AUCfirst). A PK-guided first dose resulted in achievement of target AUC with target ranges of ±10% in 50% of patients, ±15% in 75%, and ±20% in 94%. This was an improved rate of target achievement compared with the 33%, 44%, and 63% of patients who achieved the desired AUC for these respective target ranges when using weight-based dosing (P = .12, .004, and

Introduction Treatment with chimeric antigen receptor modified T cells targeting CD30 (CD30.CAR-Ts) without lymphodepletion was found to be safe with preliminary efficacy in patients (pts) with relapsed/refractory (r/r) CD30+ lymphomas (Ramos et al., JCI 2017). We report the results of a phase 1b/2 trial of CD30.CAR-Ts infused after lymphodepletion in pts with r/r CD30+ Hodgkin (HL) and Non-Hodgkin lymphoma (NHL). Objectives The primary objective of the phase Ib portion of the study was to determine the phase 2 dose of CD30.CAR-Ts using a standard 3+3 design. Methods Pts ≥ 18 years with r/r CD30+ HL or NHL having failed ≥2 prior therapies were eligible. Two dose levels were tested: 1 × 108 CAR-Ts/m2 (DL1) and 2 × 108 CAR-Ts/m2 (DL2). The first 8 pts (including the 3 pts on DL1) received bendamustine (benda) 90 mg/m2 × 2 days and the remaining 16 pts received benda 70 mg/m2 and fludarabine (flu) 30 mg/m2 × 3 days. Results At the time of data cut off (10/1/2018), 24 pts had been treated and undergone response assessment. The median age was 35.5 years (range: 23-70). 22 pts had HL, 1 had enteropathy associated T cell lymphoma and 1 had Sezary syndrome. Pts had undergone a median of 7.5 prior lines of therapy (range: 3-17). 23 pts had received prior brentuximab vedotin. 15 pts had prior autologous stem cell transplant (SCT) and 7 had prior allogeneic SCT. As there were no dose limiting toxicities, DL2 was administered as the phase 2 dose. 3 pts developed grade 1 cytokine release syndrome (CRS) and 1 pt had grade 2 CRS which responded to tocilizumab. 19 out of 24 pts had evidence of disease prior to lymphodepletion and were included in efficacy analysis. 10 pts had a CR at the 6 week assessment (53%, all in benda/flu cohort), 2 had partial response (11%), 2 had stable disease (11%), and 5 had progressive disease (26%, including all 3 pts treated at DL1). At median follow up of 180 days, the median PFS was 164 days. The median PFS for the 14 evaluable pts who received benda/flu at DL2 was 389 days. Using peripheral blood PCR, CD30.CAR-Ts peaked at wk 2 post infusion, with increasing CAR-Ts in pts receiving a higher dose or more robust lymphodepletion (3.4 × 103 ± 2.9 × 103 copies/ug of DNA for DL1-beda vs. 61 × 103 ± 41 × 103 for DL2-benda vs. 49 × 103 ± 16 × 103 for benda/flu). These differences were confirmed by flow cytometry (CD3+CAR+ cells = 13%±9% for DL1-benda vs 21%±10% for DL2-benda vs 35%±8% for benda/flu). There was also improved persistence at wk4 for higher dose and with addition of flu to lymphodepletion (0.06 × 103 ± 0.01 × 103 vs. 0.44 × 103 ± 0.41 × 103 vs. 25 × 103 ± 11 × 103/ug of DNA at wk 4 for DL1-benda, DL2-benda, and benda/flu, respectively). Conclusion CD30.CAR-Ts administered with lymphodepletion with benda/flu are safe and have promising anti-tumor activity for pts with r/r CD30+ lymphomas. A higher dose of CD30.CAR-Ts and the addition of flu to lymphodepletion increased T cell expansion and persistence and translated to improved efficacy.

s / Biol Blood Marrow Transplant 21 (2015) S266eS321 S310 Conclusion: In conclusion, although a similar rate of attrition was seen in donors overall, the reasons were different from our previous study. Two of the changes instituted are likely to have contributed (lowering joining age and increasing BMI). Further work must be done on understanding other factors associated with attrition, and collaborating with other international registries to permit access to donors who have moved to other countries.

Impact of Daptomycin Minimum Inhibitory Concentration (MIC) on Outcomes of Patients with Hematologic Malignancies and Hematopoietic Stem Cell Transplant (HSCT) Recipients with Vancomycin-Resistant Enterococci (VRE) Bloodstream Infection (BSI) Pearlie P. Chong , David van Duin , Ananta Bangdiwala , Anastasia Ivanova , Alan Kerr , David J. Weber , Peter H. Gilligan , Tippu Khan , Thomas C. Shea . 1 Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC; 2 Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC; 3 Clinical Microbiology/Immunology, McLendon Clinical Laboratories, University of North Carolina Hospitals, Chapel Hill, NC; 4 Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; 5 Department of Pharmacy, University of North Carolina, Chapel Hill, NC; 6 Bone Marrow Transplant Program, Division of Medical Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC