ALBERT

Description: Abstract 4471 Background: Patient-Reported Outcome (PRO) measures help clinicians and researchers monitor symptoms, HRQOL, satisfaction, and adherence related to cancer treatment. Symptoms affect HRQOL, and when both are reported frequently and longitudinally, a patient-reported data stream emerges that reflects physiological functioning and complements traditional laboratory and clinician-based assessments. Such data could significantly enhance risk prediction and safety monitoring in patients undergoing HCT. This study evaluates the feasibility of collecting daily and weekly PRO measurements to inform our ability to capture variation in patient experiences over time. Patients and methods: We enrolled 32 patients undergoing planned HCT (10 autologous, 11 myeloablative allogeneic, 11 reduced intensity allogeneic) in a feasibility study of frequent HRQOL and symptom surveillance following HCT. All surveys were administered electronically though patients could opt for pen and paper. PRO measures were derived from the NIH PROMIS and PRO-CTCAE measures, which have not been previously used extensively or at all in HCT patients. All patients completed a 10-question HRQOL measure (PROMIS-Global Health) and a 34-question symptom measure (a pre-selected subset of the 83-question PRO-CTCAE, with 7-day recall period) prior to HCT and weekly until D+100. Auto patients completed a daily 21-question symptom measure (a pre-selected subset of the weekly symptom surveys, with 24-hour recall period) until hospital discharge, and allo patients completed daily symptom surveys until 100 days after stem cell infusion (D+100). Kruskal-Wallis tests were used to compare groups. Median age of the sample was 55 years (range 18–70). 16 patients (50%) were female. Most auto patients had myeloma (N=8, 80%) and most allo patients had acute leukemia (16, 72%); other diagnoses included NHL (4), CML, MDS and AA. Twenty-six (81%) patients were Caucasian, 4 (12.5%) were African American, 2 were other (6.2%). Thirteen (41%) had a high school education or lower. Results: Median daily survey completion percentages prior to hospital discharge for surviving patients were 94% among auto patients, 90% among reduced intensity allo patients and 70% among myeloablative allo patients (p=0.07). Prior to D+100, median daily survey completion percentages were 87% among reduced intensity allo patients and 58% among myeloablative allo patients (p=0.004). Median weekly survey completion percentages prior to hospital discharge were 100% in all cohorts. Prior to D+100, these were 100% in auto and reduced intensity allo cohorts, and 80% among myeloablative allo patients (p=0.002). Daily surveys were completed in a median of 3 minutes, and longer weekly surveys in a median of 4.3 minutes. 93% of respondents were satisfied with survey length and 85% of respondents were satisfied with the electronic self-report system. Median weekly total symptom scores (higher scores indicated greater symptom severity) prior to conditioning were 16 in autos, 12 in myeloablative allos, and 5 in reduced intensity allos (p=0.3) and at D+7 were 23 in autos, 40 in myeloablative allos and 18 in reduced intensity allos (p=0.01). For the physical health subscale of the PROMIS measure (lower scores indicated greater impairment), baseline mean weekly HRQOL scores were 47.7 in autos, 50.8 in myeloablative allos and 50.8 in reduced intensity allos (p=0.9). By D+7, mean HRQOL scores were 37.4 in autos, 37.4 in myeloablative allos and 52.5 in reduced intensity allos (p=0.005). Conclusion: Frequent symptom and HRQOL surveillance is feasible and acceptable to HCT patients, and survey data correlates with toxicity and physiological function after transplant. Compliance rates were lower in myeloablative allo patients, especially for daily surveys, perhaps reflecting the higher burden of critical illness in this population. Future studies may be enhanced by caregiver-reported proxy data. Analyses of weekly symptom and HRQOL surveys beyond D+7, daily surveys, symptom clusters, biologic correlates and individualized profiles are ongoing. Larger studies are warranted to explore and develop risk prediction models based on this technique. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Infusion of chimeric antigen receptor modified T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) in the absence of lymphodepleting chemotherapy has been shown to be safe with responses seen in patients (pts) with relapsed/refractory (r/r) CD30+ lymphomas (Ramos et al., JCI 2017). We present here the results of a phase 1b/2 trial of CD30.CAR-Ts administered after lymphodepleting chemotherapy in pts with r/r CD30+ Hodgkin (HL) and Non-Hodgkin lymphoma (NHL). Methods: The primary objective of the phase 1b portion of the study was to determine the recommended phase 2 dose level (RP2DL) of CD30.CAR-Ts using a standard 3+3 design. Two dose levels were tested: 1 x 108 CAR-Ts/m2 (DL1) and 2 x 108 CAR-Ts/m2 (DL2). For lymphodepletion, the first 8 pts (including the first 3 pts treated at DL1) received 2 days of bendamustine (benda) 90 mg/m2, while the 10 remaining pts received 3 days of benda 70 mg/m2 and fludarabine (flu) 30 mg/m2, except for one pt who received only 1 day of benda and flu due to possible benda toxicity. Inclusion criteria were age ≥ 18 years, CD30+ disease, and r/r HL or NHL having failed ≥2 prior therapies. Results: At the time of data cut off (7/1/2018), 18 pts with a median age of 40.5 years (range: 23-70) had received CD30.CAR-Ts and undergone response assessment. Sixteen pts had HL, 1 had enteropathy associated T cell lymphoma, and 1 had Sezary syndrome. All pts were heavily pre-treated with a median of 8.5 prior therapies (range: 4-17). All pts had received prior brentuximab vedotin and 13 had prior checkpoint inhibitor therapy. Fourteen pts had prior autologous stem cell transplant (SCT) and 7 had prior allogeneic SCT. Treatment was well tolerated with no dose limiting toxicities; as a consequence, the highest dose level of CAR-T cells (2 x 108 CAR-Ts/m2) was given as the RP2DL. Three pts developed cytokine release syndrome (CRS) (grade 1: 2 pts and grade 2: 1 pt). Grade 1 CRS resolved spontaneously, while the pt with grade 2 CRS responded to tocilizumab. No neurotoxicity was observed. Out of the 18 pts, 4 were in a complete response (CR) before infusion due to bridging chemotherapy and remained disease free at 6 wk follow up. Two of these pts have since relapsed with PFS of 3.8 months and 11.9 months while the other 2 pts are still in CR after 1 year of follow up. The 14 pts with evidence of disease pre-lymphodepletion were included in efficacy analysis. Of these 14 pts, 6 had a CR (43%, all in the benda/flu cohort), 1 had partial response (7%), 2 had stable disease (14%) and 5 had progressive disease (35%) at disease assessment. No responses occurred in the 3 pts treated at DL1. At median follow up of 138 days, the median PFS was 129 days. The median PFS for the 3 evaluable pts who received benda at DL1 was 55 days vs 172 days for the 9 pts who received benda/flu at DL2 (p = 0.039). The median PFS for the 2 evaluable pts at DL2 who received benda lymphodepletion was 85.5 days but this was not included in the comparison due to small sample size. Two out of 14 evaluable pts remain in CR at 1 year. Using PCR on peripheral blood, CD30.CAR-Ts were found to be increased in the circulation of all pts, peaking at wk 2 post infusion, with increasing CAR-T cells in pts receiving greater number of CAR-T cells or more robust lymphodepletion (3.4x103 ± 2.9x103 copies/ug of DNA for DL1-beda vs. 61x103 ± 41x103 for DL2-benda vs. 59x103 ± 22x103 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). Persistence was also related to dose level and lymphodepletion (0.06x103 ± 0.01x103 vs 0.44x103 ± 0.41x103 vs 28x103 ± 15x103/ug of DNA at wk 4 for DL1-benda, DL2-benda, and benda/flu, respectively). Although both lymphodepletion regimens reduced the lymphocyte counts, only the combination of benda/flu was found to have a significant increase in IL-15 and IL-7 cytokines (13 fold, p

Description: Abstract 4152 Background: Peak oxygen consumption (VO2peak, in mL/kg*min) is assessed by cardiopulmonary exercise testing (CPET) and reflects overall physical fitness. VO2peak has prognostic value in healthy and chronically ill patients, including patients with solid tumor malignancies. To our knowledge, direct measurement of peak oxygen uptake has not previously been examined in patients undergoing HCT, an area in which prognostic models are needed to understand and limit treatment-related toxicity. Current HCT prognostic models measure disease-related risk or indirectly measure patient fitness by assessing comorbidity burden. The purpose of this study was to evaluate the feasibility of assessing functional status in HCT patients by exercise testing and physiological measurements, and to investigate the potential prognostic usefulness of these variables in this population. Patients and methods: We evaluated the feasibility of assessing cardiopulmonary fitness (CPET with gas exchange on cycle ergometer), body composition (Dual Energy X-ray Absorptiometry-DEXA), and physical function (6 minute walk test-6MW) in 32 patients undergoing planned HCT (10 autologous HCT patients, 11 myeloablative allogeneic HCT patients, 11 reduced intensity allogeneic HCT patients). Tests were conducted prior to receipt of conditioning chemotherapy and again at 100 days following stem cell infusion (D+100). Feasibility was determined by the ability of patients to successfully and safely complete a full set of tests. Exploratory analyses to investigate the relationships of variables with one another and with survival utilized Kruskal-Wallis and Wilcoxon Signed Rank tests, Pearson Correlation coefficients, and Cox regression analyses. Median age of the sample was 55 years (range 18–70). Sixteen patients (50%) were female. Most autologous HCT patients had myeloma (N=8, 80%) and most allogeneic HCT patients had acute leukemia (16, 72%); other diagnoses included NHL (4), CML, MDS and AA. Twenty-six patients (84%) had intermediate or late stage disease, and 16 patients (50%) had a Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score of 〉 3. Results: VO2peak testing was successfully completed prior to HCT in 29 (91%) patients with no adverse events during testing. Two patients had lower limb limitations preventing participation in cycle ergometry, and one patient had baseline EKG abnormalities with exclusion per clinician discretion. No significant differences in median VO2peak were observed at baseline among patients undergoing autologous, myeloablative allogeneic, and reduced intensity allogeneic HCT (20.1 (15.20–28.0), 20.8 (9.2–35.4), and 23.8 (10.8–28.7) mL/kg*min respectively, p=0.9). Across cohorts, eight (28%) patients had a VO2peak