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Patients with cancer are ideally screened for symptoms, including distress, using patient-reported outcome measures (PROMs). This initiative was developed to ensure patients without access to an electronic portal were screened for distress and related symptoms during the COVID-19 pandemic. Prior to the pandemic, these patients could complete screening in clinic. However, many visits transitioned to telehealth. We implemented a standardized telephone outreach process targeting patients without active electronic portal accounts to improve remote symptom monitoring. Outreach resulted in 172 completed screens, identifying 110 needs for 63 individuals. Twenty-eight patients completed patient portal enrollment. Outreach calls captured a higher percentage of Black patients (34%) and a higher percentage of 61-80 year olds (69%) compared to portal users. Telephone outreach during the pandemic captured data that otherwise would have been missed in elderly and minority patients without electronic patient portal access. Patient engagement is vital to the distress screening process.

Purpose: “In situ vaccination” using immunogene therapy has the ability to induce polyclonal antitumor responses directed by the patient's immune system. Experimental Design: Patients with unresectable malignant pleural mesothelioma (MPM) received two intrapleural doses of a replication-defective adenoviral vector containing the human IFNα2b gene (Ad.IFN) concomitant with a 14-day course of celecoxib followed by chemotherapy. Primary outcomes were safety, toxicity, and objective response rate; secondary outcomes included progression-free and overall survival. Biocorrelates on blood and tumor were measured. Results: Forty subjects were treated: 18 received first-line pemetrexed-based chemotherapy, 22 received second-line chemotherapy with pemetrexed (n = 7) or gemcitabine (n = 15). Treatment was generally well tolerated. The overall response rate was 25%, and the disease control rate was 88%. Median overall survival (MOS) for all patients with epithelial histology was 21 months versus 7 months for patients with nonepithelial histology. MOS in the first-line cohort was 12.5 months, whereas MOS for the second-line cohort was 21.5 months, with 32% of patients alive at 2 years. No biologic parameters were found to correlate with response, including numbers of activated blood T cells or NK cells, regulatory T cells in blood, peak levels of IFNα in blood or pleural fluid, induction of antitumor antibodies, nor an immune-gene signature in pretreatment biopsies. Conclusions: The combination of intrapleural Ad.IFN, celecoxib, and chemotherapy proved safe in patients with MPM. OS rate was significantly higher than historical controls in the second-line group. Results of this study support proceeding with a multicenter randomized clinical trial of chemo-immunogene therapy versus standard chemotherapy alone. Clin Cancer Res; 22(15); 3791–800. ©2016 AACR.

Gene-mediated cytotoxic immunotherapy (GMCI) is an immune strategy implemented through local delivery of an adenovirus-based vector expressing the thymidine kinase gene (aglatimagene besadenovec, AdV-tk) followed by anti-herpetic prodrug valacyclovir. A phase I dose escalation trial of GMCI followed by chemotherapy was conducted in patients with malignant pleural effusion (MPE). AdV-tk was administered intrapleurally (IP) in three cohorts at a dose of 1 × 10(12) to 10(13) vector particles. Primary endpoint was safety; secondary endpoints included response rate, progression-free survival, and overall survival. Nineteen patients were enrolled: median age 67 years; 14 with malignant mesothelioma, 4 non-small-cell lung cancer (NSCLC), and 1 breast cancer. There were no dose limiting toxicities. All 3 patients in cohort 2 experienced transient cytokine release syndrome (CRS). Addition of celecoxib in cohort 3 reduced the incidence and severity of CRS (none > grade 2). Three patients are alive (23–33 months after GMCI), and 3 of 4 NSCLC patients had prolonged disease stabilization; one is alive 29 months after GMCI, 3.6 years after initial diagnosis. GMCI was safe and well tolerated in combination with chemotherapy in patients with MPE and showed encouraging response. Further studies are warranted to determine efficacy.

7509 Background: Immunotherapy with anti-CD19 CART cells induces complete remission (CR) in the minority of patients with CLL, but where CRs occur they tend to be durable. Based on preclinical evidence of synergy, we combined anti-CD19 CAR T cells with ibrutinib to test the hypothesis that pre- and concurrent treatment would enhance the CR rate. Methods: This is a pilot trial of anti-CD19 CAR T cells in adults with CLL/SLL who were not in CR despite at least 6 months of ibrutinib. Pts must have failed at least 1 regimen before ibrutinib, unless they had del(17)(p13.1) or a TP53 mutation. T cells were lentivirally transduced to express a CAR comprising CD3z, 4-1BB, and humanized anti-CD19 scFv (CTL119). Pts were lymphodepleted 1 week before infusion. Ibrutinib was continued throughout the trial. Results: Manufacturing was successful in all pts. Ten pts (9M, 1F; ages 47-77; 0-12 regimens prior to ibrutinib) have been infused. All had abnormalities of TP53 or ATM and two pts had increasing BTK C481S clones. Median marrow CLL burden was 10% (range 10-50%). The median follow-up is 6 months (range 0.5-9). Cytokine release syndrome (CRS) developed in 9 pts; gr1 in 2, gr2 in 6 and gr3 in 1 pt. One pt developed gr4 tumor lysis syndrome. Treatment of CRS with the IL-6 receptor antagonist tocilizumab was not required. At 3 months, 8 evaluable pts had achieved an MRD-ve marrow CR (89%) by 9-color flow, and all remain in marrow CR at last F/U. There was modest residual splenomegaly in 3/5 patients, and adenopathy resolved in 4/6 subjects with progression in 1/6. MRD assessment by deep sequencing will be presented. Conclusions: We observed 89% MRD-ve marrow CR in pts with high-risk CLL using a well-tolerated combination of CART cells and ibrutinib. Longer follow-up will reveal the durability of these results and could support evaluation of a first-line combination approach in an attempt to obviate the need for chronic therapy. Clinical trial information: NCT02640209.

3081Background: GMCI is a tumor-specific immune-stimulator through local delivery of aglatimagene besadenovec, an adenovirus-based vector expressing the HSV-1 thymidine kinase gene (AdV-tk) followe...