The results of this prospective study suggest a substantial impact on outcome for upfront autoSCT in PTCL and should be further evaluated in randomized trials. Pretransplantation treatment needs to be improved to increase the transplantation rate.

BackgroundMore than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis.Methodology/Principal FindingsData was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17) and RCC (12). Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD) amounted to a clinical benefit rate (CBR) of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403) revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5–44.1) and in RCC (OR 8.4, 95% CI 1.3–53.0). Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC) as well as access to draining lymph nodes on clinical outcome could be demonstrated.Conclusions/SignificanceAs a ‘proof of principle’ a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines.

Background: Relapsed/refractory (R/R) Hodgkin lymphoma (HL) remains a significant clinical challenge. We hypothesized that using an immune checkpoint inhibitor to activate the immune cells in the tumor microenvironment, and concurrently targeting tumor cells with the CD30 antibody-drug conjugate brentuximab vedotin (BV) could overcome resistance. E4412 is a Phase 1 ECOG-ACRIN sponsored study of the combinations of BV and ipilimumab (Ipi) and nivolumab (Nivo) in patients with R/R HL. Here we present the updated safety and response data on the full cohort of patients treated with BV + Nivo (Arms D-F). Methods: Patients with confirmed R/R HL were treated with Nivo 3 mg/kg and BV 1.2 mg/kg (Arm D) or 1.8 mg/kg (Arm E) with a 3 + 3 design, and an expansion cohort (Arm F) of 9 patients. BV and Nivo are given every 21 days for 16 cycles; Nivo may be continued for an additional year. Dose limiting toxicity (DLT) was defined within the first cycle of therapy. Results: As of 3/10/17 19 patients (1 ineligible) have been treated. Median age was 40, range (21-70); 9 patients were male. Patients were treated with a median of 3 prior therapies. Eight patients had prior SCT; 4 patients had prior BV. Safety: Nineteen of 19 patients are evaluable for safety. There were 2 significant treatment related adverse events (AEs): 1 patient in Arm E experienced a DLT (pneumonitis grade 3 with grade 3 dyspnea and hypoxia, and typhilits), and made a full recovery; 1 elderly patient in Arm F had grade 5 pneumonitis occurring in cycle 2. There were no other Grade 4 or 5 AEs; grade 3 AEs were one each: rash, puritis, and neutropenia. The most common grade 1-2 AEs were: transaminitis (9), peripheral sensory neuropathy (8), and rash (6); other grade 1-2 AEs included: diarrhea (4), blurry vision (3), and myalgias (2). One grade 1-2 infusion reaction was noted, this patient was able to receive subsequent therapy with pre-medication. Response: Response is shown below in Figure 1. Seventeen of 18 eligible patients are evaluable for response, one patient died after cycle 2 and response could not be assessed. The overall response rate (ORR) for the combination was 89%, with a CR rate of 50% (9/18) (95% CI: 26%-74%). There were 2 CRs and 1 PR in patients treated with prior BV. The 6 month PFS is 91% (95% CI: 75-100%), and median OS with a median follow-up of 6 months is not reached. Conclusion: In this study of the combination of Nivo and BV for R/R HL, therapy was generally well tolerated, however two patients experienced pneumonitis. In a heavily pretreated patient population, the ORR of 89% and CR rate of 50% suggests a deepening of response compared to either therapy alone. Optimization of this strategy is planned with ongoing accrual to cohorts receiving BV + Ipi + Nivo. Data will be updated to include longer term PFS and OS by the time of the meeting.