Ginos, Brenda

2500 Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach for relapsed refractory hematologic malignancies. The Indiana strain of Vesicular Stomatitis Virus was engineered to encode interferon beta (IFNβ) and sodium iodine symporter (NIS) to produce VSV-IFNβ-NIS. Virally encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. NIS was inserted to noninvasively assess viral biodistribution using SPECT/PET imaging. We present the results of the phase 1 clinical trial NCT03017820 of systemic administration of VSV-IFNβ-NIS among patients (pts) with relapsed refractory Multiple Myeloma (MM), T cell Lymphoma (TCL) and Acute myeloid Leukemia (AML). Methods: VSV-IFNβ-NIS was administered at 5x109 TCID50 (50% tissue culture infectious dose) dose level 1 to dose level 4, 1.7x1011 TCID50. The primary objective was to determine the maximum tolerated dose of VSV-IFNβ-NIS as a single agent. Secondary objectives were determination of safety profile and preliminary efficacy of VSV-IFNβ-NIS. Correlative objectives included monitoring viremia and virus shedding. Adverse events (AEs) are reported based on CTCAE V4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014) criteria. Results: 15 pts received VSV-IFNβ-NIS: MM (7), TCL(7) and AML(1); 3 pts were treated at each dose level (DL) 1 through 3 (respectively 0.05, 0.17, and 0.5 x 1011 TCID50), & 6 pts were treated at dose level 4 (1.7x1011 TCID50). There were no dose limiting toxicities. The most frequent grades 3 & 4 AEs were hematologic: lymphopenia (46.6 & 26.6%), neutropenia (13.3% & 6.7%). CRS grades 1 (6.7%) and 2 (46.6%) were the non-hematologic AEs of note; mostly at DL 4. Only 1 pt required transient pressor support. Responses were seen in pts with T cell lymphoma. At DL2, there was a partial response (PR) lasting 3 months in a pt, post 12 prior lines of therapy. At DL4 there was a 6 month PR in a pt with PTCL and another pt with cutaneous relapse of PTCL who enjoys an ongoing CR, more than 1 year post VSV infusion; both pts received 5 prior lines of therapy. Viremia was detected in all pts at the end of infusion only up to 72 hrs post infusion; no infectious virus was recovered in buccal swabs or urine. Neutralizing anti-VSV antibodies were present by day 29. IFN levels were detectable within 30 mins of infusion, peaking between 4 & 48 hrs. TCL pts mounted higher hIFNβ levels within 48 hrs; the pt with CR mounted peak hIFNβ response of 18213.3pg/ml at 48 hrs post infusion, 15-fold higher than any other pt. Conclusions: VSV-IFNβ-NIS can be safely administered by IV infusion among heavily pretreated pts with hematologic malignancies. VSV-IFNβ-NIS as a single agent appears to be most effective at DL4 among patients with TCL, with an ongoing CR in a patient at DL4 more than 1 year post administration. Future trials of combination strategies with immune-modulatory drugs are currently being planned. Clinical trial information: NCT03017820.

Abstract Background Racial disparities in patient-reported outcomes (PROs; e.g., symptoms, financial burden) among patients with cancer are well documented. Prior studies have attributed such disparities to patient- and provider-level factors, but less is known about the contribution of practice-level factors. Hospital racial composition of patients has been linked to disparities in care quality and outcomes, but questions remain regarding whether oncology practice racial composition mediates racial disparities. Using 2017-2020 data from the Patient-Reported Outcomes to Enhance Cancer Treatment (PRO-TECT) trial (ClinicalTrials.gov NCT03249090), we examined racial disparities in PROs among patients with metastatic cancer, and whether oncology practice racial composition accounted for observed disparities. Methods Our sample included 1099 patients (n=198 Black; n=901 White) from 51 community oncology practices across the US. Predictors of interest were patient race (Black vs. White) and practice-reported racial composition (Black patient population >20% vs. ≤20%). Patient-reported outcome metrics included pain, appetite loss, fatigue, nausea, dyspnea, insomnia, constipation, diarrhea, and financial burden, measured at baseline and at 1- and 3-month follow-up using the EORTC Quality of Life Core Questionnaire (QLQ-C30). Raw EORTC QLQ-C30 scores were standardized to range from 0 (best) to 100 (worst). We estimated multilevel linear mixed models predicting each PRO as a function of patient race, adjusting for clinical and sociodemographic factors, followed by further adjustment for practice racial composition. Results Twelve out of fifty-one (23.5%) practices reported a Black racial composition of >20%, with 41.6% of Blacks and 14.5% Whites receiving care at these practices. Across all practices, Blacks reported worse pain (β=5.5, p=0.02), nausea (β=2.5, p=0.04) and financial burden (β=7.6, p<0.01), but less fatigue (β=-4.1, p=0.05) when compared with Whites. Regardless of race, patients receiving care at practices with a Black racial composition of >20% reported more pain (β=5.5, p=0.01), appetite loss (β=8.1, p<0.01), fatigue (β=5.1, p=0.01), nausea (β=2.3, p=0.05), dyspnea (β=4.3, p=0.04), and insomnia (β=4.8, p=0.03) than patients receiving care at practices comprised of ⇐20% Blacks. Practice racial composition did not mediate racial disparities in PROs. Conclusion Racial disparities in PROs were observed among patients treated at US community oncology practices. Practice racial composition was associated with multiple PROs, regardless of patient race, but racial disparities in PROs were not explained by practice racial composition. These findings suggest that identifying and addressing the needs of practices serving a disproportionate share of Black patents may be one effective strategy to mitigate practice-level disparities in cancer outcomes. Citation Format: Cleo A. Samuel, Olive Mbah, Wendi Elkins, Marjory Charlot, Amylou Dueck, Brenda F. Ginos, Jennifer Jansen, Deborah Schrag, Patty Spears, Angela Stover, Ethan Basch. Separate and unequal: Examining the role of race and site of care on patient-reported outcomes among patients with metastatic cancer (AFT-39) [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-119.

Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach for relapsed refractory hematologic malignancies. The Indiana strain of Vesicular Stomatitis Virus (VSV) has been engineered to encode interferon beta (IFNβ) and sodium iodine symporter (NIS) to produce VSV-IFNβ-NIS. The virally encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. The NIS is inserted as a reporter gene into the viral genome to enable noninvasive monitoring of viral spread using PET/CT imaging. Here we present results of Arm A (patients with low tumor burden) of the Phase I clinical trial (NCT03017820) of intravenous administration of VSV-IFNβ-NIS for patients (pts) with relapsed refractory hematological malignancies: MM, AML, and TCL. Methods: This was a classical 3+3 phase I trial, starting at 5x10^9 TCID50 (50% tissue culture infectious dose) level 1 through 1.7x10^11 TCID50 dose level 4 given as a single IV dose. The primary objective was determining the maximum tolerated dose of VSV-IFNβ-NIS alone; secondary objectives include estimating the safety profile and preliminary efficacy. Correlative objectives include monitoring the pharmacodynamics of viral replication through SPECT/CT imaging with NIS gene, viremia, virus shedding and changes in the immune profile of peripheral blood leukocytes. Adverse events (AEs) are reported based on CTCAE v4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014; 124(2):188-195) criteria. Results: From April 2017, 12 pts have received IV VSV-IFNβ-NIS in Arm A: MM (7), TCL(4) and AML(1); 3 pts were treated at each dose level (DL) 1 to 4. At DL1, there were five grade 3 hematologic AEs (leukopenia [1], neutropenia [1], lymphopenia [3]) and no grade 3+ non-hematologic AEs. At DL2, three grade 3 hematologic AEs (anemia [2], lymphopenia [1]), four grade 4 hematologic AEs (neutropenia [1], leukopenia [1], lymphopenia [1] and thrombocytopenia [1]). There was 1 event of grade 2 CRS at DL2, two grade 3 non-hematologic AEs (nausea [1], dehydration [1]). At DL3, there was one grade 4 hematologic AE (neutropenia [1]), three grade 3 hematologic AEs (lymphopenia [2], leukopenia [1]), and one grade 3 non-hematologic AE (vasovagal reaction [1]). One grade 2 and grade 1 CRS by Lee criteria were observed. At DL4, there were three grade 3 hematologic AEs (lymphopenia [1], neutropenia [1], thrombocytopenia [1]), and three grade 3 non-hematologic AEs (AST increase [1], skin infection [1], soft tissue infection [1])and two grade 2 CRS. There were no dose limiting toxicities. There was one partial response (DL2) and one complete response (DL4); 3 pts had stable disease, 7 pts progressed. The MM pts receiving VSV-IFNβ-NIS at DL4 had stable disease. Six of the 7 MM pts demonstrated transient reduction in serum level of involved free light chain (LC) after VSV-IFNβ-NIS infusion, with median 20.4% reduction of the involved LC within 48 hrs. Viremia was detectable in all pts at the end of infusion, to varying levels at 30 mins, 1, 2, 4, 24, 48h or 72 hrs post infusion. No persistent viremia was observed. No infectious virus was recovered in buccal swabs or urine and neutralizing anti-VSV antibodies were present by day 29. The IFN levels were detectable within 30 minutes of infusion and peaked between 4 and 48 hrs. The pts with a diagnosis of TCL mounted higher hIFNβ levels within 48 hrs. Remarkably, the TCL pt with CR (DL4) mounted a peak hIFNβ response of 18213.3pg/ml at 48 hrs post infusion, approximately 15-fold higher than any other pt enrolled in the study; and highest neutralizing antibody titer (1:40960). Conclusion: VSV-IFNβ-NIS can be safely administered by intravenous infusion in pts with hematological malignancies, up to a dose level of 1.7 x 1011 TCID50, without dose limiting toxicities and no CRS higher than grade 2. In this small phase 1 study, pts with T-cell lymphoma demonstrated the strongest signal of response, with one confirmed partial response at DL2 and one complete response at DL4. IFNβ is an early biomarker of tumor susceptibility; the magnitude of IFNβ elevation appears to correlate with treatment response. There were no confirmed responses in pts with MM, but the 20.4% transient reduction in LC suggests that combination strategies with VSV-IFNβ-NIS may result in deeper and sustained responses in MM. Future trials investigating combination strategies with immune modulatory drugs are being planned. Disclosures Peng: Imanis: Other: Equity Ownership. Witzig:Karyopharm Therapeutics: Research Funding; Immune Design: Research Funding; Spectrum: Consultancy; Incyte: Consultancy; Acerta: Research Funding; MorphSys: Consultancy; AbbVie: Consultancy; Celgene: Consultancy, Research Funding. Dispenzieri:Intellia: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Alnylam: Research Funding; Janssen: Research Funding; Celgene: Research Funding. Gertz:Celgene: Consultancy; Annexon: Consultancy; Sanofi: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Data Safety Monitoring board from Abbvie: Membership on an entity's Board of Directors or advisory committees; NCI SPORE MM: Research Funding; Johnson and Johnson: Speakers Bureau; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; Advisory Board for Proclara: Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy; Ionis/Akcea: Consultancy; Spectrum: Consultancy, Research Funding; Prothena: Consultancy; DAVA oncology: Speakers Bureau; i3Health: Consultancy; Advisory Board for Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; International Waldenstrom Foundation: Research Funding. Dingli:Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy; Karyopharm Therapeutics: Research Funding; Millenium: Consultancy; Sanofi-Genzyme: Consultancy. Kapoor:Cellectar: Consultancy; Celgene: Honoraria; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Lin:Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy. Kumar:Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Cellectar: Other; Carsgen: Other, Research Funding; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Sanofi: Research Funding; Dr. Reddy's Laboratories: Honoraria; Adaptive Biotechnologies: Consultancy; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; MedImmune: Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Karyopharm: Consultancy; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; BMS: Consultancy, Research Funding; Genecentrix: Consultancy; Tenebio: Other, Research Funding. Russell:Imanis: Other: Equity Ownership. OffLabel Disclosure: This describes of administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and human interferon, in Patients with Relapsed or Refractory Hematologic malignacies

Background:Case reports suggest photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an effective treatment for refractory mycosis fungoides (MF). No prospective trials have examined the use of ALA-PDT in MF. Objective:We aimed to assess the efficacy of ALA-PDT in refractory MF. Methods:This was a prospective study at Mayo Clinic in Scottsdale, Arizona in patients ≥ 18 years with plaque-stage treatment-refractory MF. Monthly sessions of ALA with blue light PDT were administered for up to six months. Responses were measured by Composite Assessment of Index Lesion Severity (CAILS) and Physician Global Assessment (PGA). Ad hoc analysis with modified CAILS (mCAILS) was performed, eliminating hyperpigmentation from scoring. Results:Eleven patients (30 total lesions) were treated. Six patients completed the trial per protocol. Objective response rates were 36.4% by PGA (10.9-69.2%), 18.2% by CAILS (2.3-51.8%), and 36.4% by mCAILS (10.9-69.2%). Limitations:Five patients did not complete all six PDT cycles per protocol, possibly accounting for reduced efficacy. Conclusion:ALA-PDT with blue light irradiation was moderately effective and well tolerated in refractory plaque stage MF. Lower response rates compared to similar trials may be partially explained by utilization of strict lesional assessment criteria and other variations in methodology. Disclosures Mangold: MiRagen:Research Funding;Sun Pharma:Research Funding;Elorac:Research Funding;Kirin:Membership on an entity's Board of Directors or advisory committees;Solagenix:Research Funding. OffLabel Disclosure: Photodynamic therapy is a two-step therapy in which a drug that acts as a photosensitizer is administered to target a diseased tissue, followed by illumination with visible light to activate the drug and destroy the target tissue. PDT has been used to treat internal cancers as well as treatment of cancer and precancer of the skin.

PURPOSE There is increasing interest in implementing digital systems for remote monitoring of patients’ symptoms during routine oncology practice. Information is limited about the clinical utility and user perceptions of these systems. METHODS PRO-TECT is a multicenter trial evaluating implementation of electronic patient-reported outcomes (ePROs) among adults with advanced and metastatic cancers receiving treatment at US community oncology practices (ClinicalTrials.gov identifier: NCT03249090 ). Questions derived from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) are administered weekly by web or automated telephone system, with alerts to nurses for severe or worsening symptoms. To elicit user feedback, surveys were administered to participating patients and clinicians. RESULTS Among 496 patients across 26 practices, the majority found the system and questions easy to understand (95%), easy to use (93%), and relevant to their care (91%). Most patients reported that PRO information was used by their clinicians for care (70%), improved discussions with clinicians (73%), made them feel more in control of their own care (77%), and would recommend the system to other patients (89%). Scores for most patient feedback questions were significantly positively correlated with weekly PRO completion rates in both univariate and multivariable analyses. Among 57 nurses, most reported that PRO information was helpful for clinical documentation (79%), increased efficiency of patient discussions (84%), and was useful for patient care (75%). Among 39 oncologists, most found PRO information useful (91%), with 65% using PROs to guide patient discussions sometimes or often and 65% using PROs to make treatment decisions sometimes or often. CONCLUSION These findings support the clinical utility and value of implementing digital systems for monitoring PROs, including the PRO-CTCAE, in routine cancer care.

Abstract Background: We previously reported successful treatment of myeloma with an oncolytic virus, MMV-NIS. Preexisting immunity against measles made use of that virus unsatisfactory. The Indiana strain of Vesicular Stomatitis Viruses (VSV) are being developed as anticancer drugs for the treatment of a variety of malignancies. To ensure tumor selective replication and spread, we designed the VSV to encode interferon beta. Expression of IFNβ also serves as a STING agonist to activate host immunity against the cancer. The sodium iodide symporter (NIS) is inserted as a reporter gene into the viral genome to enable noninvasive monitoring of viral spread using PET/CT imaging. We report a Phase I clinical trial of intravenous administration of VSV-IFNβ-NIS for relapsed hematological malignancies including MM, AML, and TCL. Methods: Arm A consisted of patients with low tumor burden. Arm B included patients with high tumor burden. Both arms consisted of a classical 3+3 phase I trial, starting at 5x10^9 TCID50 (dose level 1) through 5x10^11 TCID50 (dose level 4), given as a single IV dose. In order to obviate potential toxicity from high interferon levels, Arm B received ruxolitinib 15 mg twice daily for 10 days beginning on day -1. The primary objective was determining the maximum tolerated dose (MTD) of VSV-IFNβ-NIS alone and in combination with ruxolitinib; secondary objectives include estimating the safety profile and preliminary efficacy. Correlative objectives include monitoring the pharmacodynamics of viral replication through SPECT/CT imaging with NIS gene, viremia, virus shedding, changes in the immune profile of peripheral blood leukocytes, and immunohistochemistry for immune cell infiltrates in tumors. Adverse events (AEs) are reported herein based on CTCAE v4 with the exception of cytokine release syndrome (CRS) which is based on Lee (Blood 2014; 124(2):188-195) criteria. Results: To date, 10 patients have received IV VSV-IFNβ-NIS; 8 in Arm A and 2 in Arm B. In Arm A, 3 patients were treated at dose level 1, 3 at dose level 2 and 2 at dose level 3. At dose level 1, there were three grade 3 hematologic AEs (neutropenia [1], lymphopenia [2]), and no grade 3+ non-hematologic AEs. At dose level 2, there were two grade 3 hematologic AEs (anemia [1], lymphopenia [1]), and two grade 3 non-hematologic AEs (nausea [1], dehydration [1]). A grade 2 CRS by Lee criteria was also observed. At dose level 3, 2 patients have been enrolled and data are maturing for DLT evaluation. In Arm B (VSV + rux), 2 patients have been enrolled and data are maturing for dose limiting toxicity (DLT) evaluation. Other grade 1 and 2 toxicities have included fever, hypertension, headache, electrolyte abnormalities, nausea, vomiting, transient elevation of liver function tests and creatinine. All grade 1 and 2 toxicities resolved within 72 hours. Among the 6 patients evaluable for response, there was one partial remission (TCL patient treated at dose level 2), and 5 with progressive disease. Multiple cytokines increased at 4h post infusion of virus, but most returned to baseline levels by 24h.Viremia was detectable in all patients at the end of infusion, and to varying levels at 30 mins, 1, 2, 4, 24, 48h or 72 hours post virus infusion. No persistent viremia was observed. No infectious virus was recovered in buccal swabs or urine and neutralizing anti-VSV antibodies were present by day 29. Extensive immune phenotyping and ELIspot assays for shared antigens are ongoing. Conclusion: In the lowest dose levels tested to date, VSV-IFNβ-NIS has not led to any observed dose limiting toxicity. Dose escalation is ongoing and updated results will be reported. Disclosures Lacy: Celgene: Research Funding. Peng:Vyriad: Equity Ownership. Russell:Vyriad: Equity Ownership. Dueck:Bayer: Employment; Phytogine: Employment; Pfizer: Honoraria. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Gertz:spectrum: Consultancy, Honoraria; Physicians Education Resource: Consultancy; Ionis: Honoraria; janssen: Consultancy; Medscape: Consultancy; celgene: Consultancy; Apellis: Consultancy; Prothena: Honoraria; Amgen: Consultancy; annexon: Consultancy; Abbvie: Consultancy; Research to Practice: Consultancy; Teva: Consultancy; Alnylam: Honoraria. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding. Kapoor:Celgene: Research Funding; Takeda: Research Funding. Al-Kali:Novartis: Research Funding. Naik:Vyriad: Equity Ownership. Kumar:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract Introduction: Polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are chronic, Philadelphia-negative myeloproliferative neoplasms (MPNs) that are characterized by deregulated myeloid lineage cell production, leading to a high symptom burden, including abdominal pain/discomfort from splenomegaly, fatigue, depressive symptoms, sleep disturbance, sexual problems, and pruritis, among other symptoms. Yoga interventions have been demonstrated to be efficacious for improving symptom burden in other cancer populations. Additionally weight has been shown to moderate symptom burden response in cancer patients. In MPN patients, it is unknown if weight influences symptom burden response. Therefore, the purpose of this analysis was to examine the differences at baseline and post-intervention in symptom burden between overweight and normal weight MPN patients participating in an online yoga intervention. Methods: MPN patients were asked to participate in 60 minutes of online-streamed yoga weekly for 12 weeks. Participants were asked to complete online self-report surveys administered via Qualtrics at baseline (week 0), mid-point (week 7), post-intervention (week 12), and follow-up (week 16). Survey measures included demographics, total symptom burden and fatigue (MPN Symptom Assessment Form [MPN SAF]) as well as NIH PROMIS measures of pain, anxiety, depression, sleep, and sexual function. BMI status was determined through self-report height and weight obtained in the baseline survey. For statistical analyses, BMI was dichotomized into an overweight (OW) category (BMI ≥25 kg/m2) and a normal weight (NW) category (BMI <25 kg/m2). Results: A total of 38 MPN patients completed the 12-week intervention. The majority of participants were diagnosed with either PV (n=16) or ET (n=16), with MF being less common (n=6). Median age was 56 years (range 29-72) with most participants being female (n=34). A minority were OW (n=12). At baseline, total symptom score (TSS) was descriptively higher in OW vs NW participants (mean 42.8 [SD 16.2] vs 32.7 [SD 10.9], p=0.06) with no other differences observed for PROMIS outcomes. OW participants had significantly improved TSS (p=0.002), anxiety (p=0.002), sleep (p=0.02), and vaginal discomfort (p=0.04) at the end of the intervention (week 12, Table 1). Improvements in NW participants did not reach statistical significance for any scales except sleep at week 12 (p<0.001). From baseline to follow-up (week 16), NW participants had significant improvements in TSS (p=0.003), depression (p=0.003), and sleep (p=0.007). OW participants maintained significant improvements in only sleep at week 16 (p=0.005). Conclusion: In MPN patients participating in a 12-week, online streamed yoga intervention, some differences in response to the intervention were observed between OW and NW participants. However, statistical power for definitive analysis of weight as a moderator for improvement in symptom burden was limited due to a small sample size. Considering the lack of interventions in MPN patients and the potential role that weight has on outcomes in other cancer populations, a randomized controlled trial investigating the effects of online yoga in a larger sample of MPN patients is warranted along with further investigation of effectiveness of the intervention within groups of participants by weight. Disclosures Gowin: Incyte: Membership on an entity's Board of Directors or advisory committees. Mesa:Promedior: Research Funding; Incyte: Research Funding; Ariad: Consultancy; CTI Biopharma: Research Funding; Novartis: Consultancy; Gilead: Research Funding; Galena: Consultancy; Celgene: Research Funding.

Abstract Introduction: Polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are Philadelphia-negative myeloproliferative neoplasms (MPNs) leading to risk of vascular events, splenomegaly and cytopenias in advanced disease as well as disease-originating symptoms, including (but not limited to) fatigue, depressive symptoms, insomnia, inactivity, sexual problems, and pruritis. Current therapy with JAK inhibition has improved MPN symptom burden, yet even in responders, unmet needs remain for alleviating fatigue, mood related symptoms, and insomnia. Yoga used as non-pharmacologic therapy has been shown to be efficacious for improving anxiety, depression, sleep quality, and fatigue in other cancer populations, including hematological malignancies. Due to a lack of this type of research in MPN patients, we undertook the first yoga study in this population as a feasibility trial (i.e., acceptability, demand, practicality) of home-based, online-streamed yoga for improving MPN patient symptom burden. Methods: MPN patients were recruited nationally using social media. Participants were asked to complete 60 minutes of online-streamed yoga weekly for 12 weeks. The yoga video selection included MPN-specific videos as well as others chosen specifically with potential splenomegaly in mind. Additionally, participants were asked to complete online self-report surveys administered via Qualtrics. Survey measures included demographics, total symptom burden and fatigue (MPN Symptom Assessment Form [MPN SAF]) as well as NIH PROMIS measures of pain, anxiety, depression, sleep, and sexual function. Surveys were administered at baseline (week 0), mid-point (week 7), post-intervention (week 12), and follow-up (week 16). Weekly yoga minutes were collected through online self-report. Results:Patients: Two hundred and forty-four MPN patients completed the eligibility survey, 134 were eligible, 55 completed the informed consent, and 38 MPN patients completed the 12-week intervention. The majority of participants were diagnosed with either PV (n=16) or ET (n=16), with MF being less common (n=6). Additionally, the majority of participants were female (n=34), Caucasian (n=37), married (n=30) of a normal BMI category (n=26), and had attained a Bachelor's degree or higher (n=25). Median age of those participating was 56 years (range 29-72). Yoga Participation & Safety:Approximately 37% (n=14) of study participants averaged ≥60 min/week of yoga. Yoga participation averaged 50.8±36.2 min/week. Additionally, 75% of participants felt safe from injury while participating in online yoga. Only one adverse event was reported (irritated enlarged spleen). Feasibility:Overall, 68% of participants were either satisfied or very satisfied with online yoga and 75% felt that is was helpful for coping with MPN-related symptoms (i.e., acceptability, practicality). However, only 43% of participants reported that they were likely or very likely to continue their online yoga practice (i.e., demand). Impact of Yoga Intervention: From baseline (week 0) to post-intervention (week 12, n=30), there were significant improvements in total symptom burden (effect size [ES] in standard deviation units=-0.36, p=0.004), anxiety (ES=-0.67, p=0.002), depression (ES=-0.41, p=0.049), sleep (ES=-0.58, p<0.001), and fatigue (ES=-0.33, p=0.04). These improvements remained significant at follow-up (week 16, n=28) for all outcome measures with a trend for maintained fatigue improvement (ES=-0.34, p=0.06). There were no significant differences in outcomes between those that averaged <60 min/week of yoga compared to those that averaged ≥60 min/week of yoga. Conclusions: A 12-week, home-based, online-streamed yoga intervention is feasible (i.e., accepted, practical) for MPN patients. Although the sample size was small and there was no control group, the results suggest that online yoga may be effective for improving MPN symptom burden, with statistically significant improvements observed in total symptom burden, fatigue, anxiety, depression, and sleep. A randomized, controlled trial is warranted to evaluate home-based, online-streamed yoga on MPN patient outcomes. If effective, yoga may represent a unique non-pharmacologic complement to standard therapies in a population with a heterogeneous symptom profile and significant symptom burden. Disclosures Gowin: Incyte: Membership on an entity's Board of Directors or advisory committees. Mesa:Ariad: Consultancy; Galena: Consultancy; Incyte: Research Funding; Gilead: Research Funding; Novartis: Consultancy; Promedior: Research Funding; CTI Biopharma: Research Funding; Celgene: Research Funding.

PURPOSE The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m 2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute–sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.