Vera-Aguilera, Jesús

Introduction Neutropenic fever following high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a common (incidence 63-100%) and potentially life-threatening complication. Recommended time to antibiotic (TTA) administration is within 1 hr of fever onset with delays associated with significant morbidity, prolonged hospitalization, and mortality. Standard of care guidelines emphasize patient self-monitoring for fever, with instructions to seek immediate medical attention if body temperature (temp) reaches 100.4°F or higher. In this study, we evaluated if a novel wearable, continuous temp monitor, tPatch, could reliably estimate core body temp and detect fever in an outpatient setting following ASCT. Additionally, we gathered preliminary data to explore early detection and prediction of clinically relevant temp rise in this clinical setting. Methods Patients (N = 86) with hematologic malignancies (62% multiple myeloma) who underwent high-dose chemotherapy followed by ASCT at Mayo Clinic, MN were prospectively enrolled between June 2018 and March 2019. Patients (82% male) wore an axilla-placed tPatch continuously for 7 days in an outpatient setting during the post ASCT period and were asked to record self-measured oral temp in 3-4 hr intervals daily using a standardized thermometer after appropriate training . Patients followed standard of care procedures with daily clinic assessment of temp, blood counts, and vital signs. An optional patient questionnaire was given at end-of-study. A model was trained using both patient- and clinic-assessed oral temp measures to estimate core temp from 2 sensors on the tPatch device. Core temp estimates and trends were then compared to patient- and clinic-assessed measurements. Fever was defined as a temperature ≥100.4°F for at least 1 hr. Results When compared to all oral temp reads, the tPatch estimated core temp within 0.03 ± 0.7℉. Among the 86 patients, clinic-assessed fever incidence was 29.4% while tPatch-assessed incidence was 58.8%. Using all clinic-recorded temp readings as "ground truth," the sensitivity and specificity of the tPatch algorithm in detecting fevers were 88% and 86%, respectively, while patient self fever detection sensitivity was 62% and specificity 93%. With "fever episode" defined as a temp ≥100.4°F for at least 1 hr, tPatch detected 9.6 times the number of fever episodes vs. clinic reads. The average lead time of tPatch detection of clinic-recorded fevers was 3.7 hours. In 25% of all intervals between clinic temp readings, either tPatch or patients detected at least 1 fever episode. The tPatch was well-tolerated, the only adverse events reported were grade 1 skin irritation and discomfort in 4 (5%) patients. Of 65 patients who completed the survey, 95% reported the tPatch as "quite" or "somewhat" comfortable and 94% stated no difficulty in using the tPatch. Exploration of tPatch temp trends over various time intervals for use in fever prediction is ongoing. Conclusions Patient self-monitoring of temp has low sensitivity and is not feasible for long intervals of time (e.g., overnight). Continuous temperature monitoring by a wearable device overcomes these challenges and has the potential to improve early detection and consequently shorten time to antibiotic initiation. A follow-up randomized study is planned to assess the clinical benefits of continuous temp monitoring through patient and clinician alerts triggering early clinical intervention for febrile neutropenia. Figure Disclosures Vera-Aguilera: Verily Life Sciences: Research Funding. Haji-Abolhassani:Verily Life Sciences: Employment. Kulig:Verily Life Sciences: Employment. Heitz:Verily Life Sciences: Employment. Paludo:Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding; Celgene: Research Funding. Ghoreyshi:Verily Life Sciences: Employment. Scheevel:Verily Life Sciences: Research Funding. Schimke:Verily Life Sciences: Research Funding. Markovic:Verily Life Sciences: Research Funding.

Abstract Background: Multiple myeloma (MM) accounts for approximately 1% of all cancers and 10% of hematologic malignancies in the United States (U.S.). MM occurs in all races, but the incidence in African Americans is two to three times higher than in non-Hispanic whites. MM is also slightly more frequent in men than women (1.4:1). Many clinical trials lack appropriate representation of specific patient populations, limiting the generalizability of the evidence obtained. Therefore, we determined the representation of ethnic minorities, the elderly, and women in MM clinical trials. Methods: Enrollment data from all therapeutic trials reported as completed in clinicaltrial.gov from 2000 to 2016 were analyzed. Clinical trials including other hematologic malignancies and with recruitment outside of the U.S. were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 SEER database MM complete prevalence. Chi-square test was used to estimate differences in categorical data. Results: Out of 177 MM clinical trials (CT), 78 (44%) reported ethnicity with a total of 12,055 enrollees. Regarding enrollees' ethnic composition, 84% were non-Hispanic White (NHW), 8.6% African American (AA), 2.8% Asian, 1.8% Hispanic, and 0.1% Native American/Alaskan Indian. Out of those 78 CT, 52 (66%) were phase II, 15 (19%) phase III, and 11 (14%) phase I. Most of the results were published from 2012 to 2016 (74%). Forty-six (59%) trials were sponsored by industry, 7 (9%) by NCI, and 25 (32%) were investigator initiated. Participation in CT varied significantly across ethnic groups, NHW were more likely to be enrolled in CT (EF of 0.23) than AA (EF of 0.08, p < 0.0001) and Hispanics (EF of 0.05, p< 0.0001). Males had a higher recruitment rate than females (58% vs. 42%), but this could be explained by the higher incidence of MM in males. Enrollees' median age was 62 years. Younger patients (< 65 years) were more likely to be enrolled in CT than the elderly (66% vs. 34%, p<0.0001). Industry-sponsored trials were less likely to recruit AA compared with investigator-initiated trials (7.6% vs. 12%, p<0.01). Conclusions: Despite the higher incidence of MM in African Americans and the elderly, the former only represented 8.6% of the study participants and 66% of these were less than 65 years of age; therefore, we are lacking data in the tolerability of these new agents in our aging MM population. We also observed that industry studies were less likely to recruit AA patients. Collaborations between investigators, sponsors, and the community are necessary to increase our minority and elderly patients' access to clinical trials. Citation Format: Narjust Duma, Miguel Gonzalez Velez, Jesus Vera-Aguilera, Richardo Parrondo, Veronica Mariotti, Jonas Paludo, Yucai Wang, Ronald Go, Alex Adjei. Diversity in multiple myeloma clinical trials [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A27.

Abstract Background: Despite the importance of diversity while studying new drugs, many cancer clinical trials (CT) lack appropriate representation of specific patient populations, limiting the generalizability of the evidence obtained. Therefore, we determined the representation of ethnic minorities, the elderly, and women in cancer CT. Methods: Enrollment data from all therapeutic trials reported as completed in clinicaltrial.gov from 2003 to 2016 were analyzed. CT in rare cancers (< 1% incidence) or with recruitment outside of the United States were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 Surveillance Epidemiology and End Results (SEER) database cancer prevalence. Results: Out of 1,012 CT, 310 (31%) reported ethnicity with a total of 55,689 enrollees. 46,431 (83%) enrollees were non-Hispanic white, 3,270 (6%) African American, 2,982 (5.3%) Asian, 1,484 (2.6%) Hispanic, and 1,332 (2.4%) were classified as other. Participation in CT varied significantly across ethnic groups; non-Hispanic whites were more likely to be enrolled in CT (EF of 1.2%) than African Americans (EF of 0.7%, p <0.001) and Hispanics (EF of 0.4%, p <0.001). A decrease in African American (6% vs. 9.2%) and Hispanic (2.6% vs. 3.1%) enrollment was observed when compared with historical data from 1996 to 2002. Asians were well represented and their recruitment doubled over the past 14 years (2% vs. 5.3%). Hispanics were less represented in breast and prostate cancer CT, only contributing to 3% and 1.5% of the study population. African Americans were less represented in lung (5.4%) and renal cell carcinoma (3%) trials. Enrollees' median age was 60 years with 64% of patients <65 years of age. Younger patients (<65 years) were more likely to be enrolled in CT than the elderly (64% vs. 36%, p < 0.001). Lower recruitment of female patients was observed in CT for melanoma (35%), lung (39%), and pancreatic cancer (40%). Conclusions: African Americans, Hispanics, and the elderly were less likely to be enrolled in CT. Comparing with historical data, we observed a decrease in minorities' recruitment over the past 14 years. This change could be attributed to the increased complexity of CT and mandatory molecular testing as many minorities lack access to institutions with genetic-testing capacity. Future trials should take extra measures to recruit participants who adequately represent the U.S. cancer population. Citation Format: Narjust Duma, Jesus Vera-Aguilera, Yucai Wang, Jonas Paludo, Konstantinos Leventakos, Aaron Mansfield, Alex Adjei. Representation of minorities, the elderly, and women in over 1000 clinical trials [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A26.

Abstract Background The treatment of metastatic melanoma has been revolutionized by developments in targeted therapy and immunotherapy. BRAF/MEK inhibitors, blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death (PD-1/L1) receptor have shown durable anti-melanoma effects. The optimal sequence strategy of targeted therapy and immunotherapy in metastatic BRAF-mutated melanoma patients (pts) is unknown and no treatment guidelines exist. Therefore, we report a single-institution experience of different treatment approaches using targeted therapy and immunotherapy and its impact on outcomes. Methods Pts with BRAF-mutated metastatic melanoma treated with targeted therapy and immunotherapy from 2012 to2017 were analyzed. Six groups were identified based on treatment strategy: (1) 1st line BRAF/MEK inhibitors followed by 2nd line immunotherapy; (1.1) 1st line BRAF/MEK inhibitors followed by 2nd line immunotherapy in combination with BRAF/MEK inhibitors (triple therapy);(1.2) same as group 1 followed by triple therapy as 3rd line; (2) 1st line immunotherapy followed by 2nd line BRAF/MEK inhibitors; (2.1) 1st line immunotherapy followed by 2nd line triple therapy; (2.2) same as group2 followed by triple therapy as 3rd line. All time-to-event analysis was calculated using the Kaplan-Meier method and Wilcoxon test. Results Forty four pts were included. The median age at diagnosis was 49 years (range 21-73), 24 (54%) pts were females and 19 (43%) developed brain metastases during their disease course. BRAF V600 mutation was seen in all pts except in 1 pt with p.N581S mutation. The preferred 1st line targeted therapy was dabrafenib/trametinib used in 17 (94%) out of 18 pts, while ipilimumab was the preferred 1st immunotherapy used in 11 (42%) out of 26 pts. For 2nd line therapy, DT was used in 19 (90%) out of 21 pts, while pembrolizumab was used in 16 (69%) out of 23 pts. For 3rd line, DT was used in 5 (83%) out of 6 pts, while pembrolizumab was used in 6 (100%) out of 6 pts. DT was usually the first choice for patients with high burden disease or brain metastases. The most common approach strategy was immunotherapy followed by targeted therapy (group 2), the median duration of treatment was 11 and 19 weeks respectively; for pts started on targeted therapy followed by immunotherapy (group 1), the median duration of treatment was 17 and 14 weeks respectively. (Table 1) Time-to-next therapy (TTNT) following 1st line treatment was similar in pts treated with targeted therapy (median 23 weeks [95% CI: 15-31]) or immunotherapy (median 26 weeks [95% CI: 10-33], p=0.94). Following 2nd line treatment, the TTNT for pts treated with targeted therapy was 18 weeks (95% CI: 4-38), immunotherapy 18 weeks (95% CI: 13-19) and triple therapy 22 weeks (95% CI: 13-41), p=0.48. A trend towards better overall survival (OS) from frontline therapy was seen in pts who received immunotherapy (1st line) followed by targeted therapy (2nd line) (median 7 years [95% CI: 2.7-7.08]) compared to those who received targeted therapy (1st line) followed by immunotherapy (2nd line) (median 2.3 years [95% CI: 1.3-NR], p=0.09. Interestingly, patients who received salvage chemotherapy had significant longer OS in those treated initially with immunotherapy (median 7 years [95% CI: 3.2-7.08]) (n=6) compared to patients started on targeted therapy (median 2 years [95% CI: 0.6-2.4], p=0.03) (n=5). Conclusion A trend towards longer OS was seen in pts treated with 1st line immunotherapy followed by 2nd line targeted therapy with a median therapy time of 11 and 19 weeks respectively. No difference in TTNT was seen with the use immunotherapy, targeted therapy or triple therapy when used as 1st or 2nd line. The significant longer OS benefit with f 1st line immunotherapy was only seen in patients who received chemotherapy later in their treatment course. Table 1.Treatment Characteristics by GroupMedian duration of therapy in weeksGroup(n)1st line therapy(median)2nd line therapy(median)3rd line therapy(median)Totalmedian (range)Chemotherapy (n)1(n=9)Targeted therapy(17)Immunotherapy (14)N/A52 (13-134)51.1(n=7)Targeted therapy(25)Triple therapy (19)Any*(43)69 (22-118)11.2(n=2)Targeted therapy(60)Immunotherapy (16)Triple therapy (21)96 (81-111)12(n=18)Immunotherapy(11)Targeted therapy(19)Any*(24)48 (16-120)52.1(n=4)Immunotherapy(17)Triple therapy (16)Any*(9)41 (25-69)02.2(n=4)Immunotherapy(19)Targeted therapy(16)Triple therapy (19)61 (54-73)1* include any treatment regimen such as immunotherapy, targeted therapy or chemotherapy Citation Format: Jesus Vera-Aguilera, Jonas Paludo, Narjust Duma, Marcella Tschautscher, Cecilia Yu, Svetomir Markovic. A clinical insight into therapeutic sequence in advanced melanoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A32.