Citations

e18521 Background: About 40% of the US population are from minority groups. Minority pts are under-represented in oncology clinical trials, which limits the applicability of results to the general population and perpetuates poor relationships between healthcare systems and minority communities. This assessment investigated underlying causes of this lack of minority representation in clinical trials and proposes plans to promote diversity. Methods: To better understand the limited inclusion of under-represented pts in oncology clinical trials, 10 specialists in cancer care were selected to provide their perspectives. Specialists were chosen because of their experience enrolling minority pts in clinical trials and met virtually in Dec 2020 via Within3, a secure digital communication platform, to discuss obstacles faced in recruiting minority pts and potential strategies to address these concerns. Specificity and alignment in responses were achieved through software analytics and follow-up queries. Results: The 10 specialists identified as Asian (10%), Black (30%), White (50%), and Hispanic (10%), and began practicing medicine in the 1980s-2010s. All are involved in clinical research and treat a range of minority pts in both urban and suburban settings. Most specialists (8/10) reported treating > 20 minority pts with cancer annually. However, few specialists (2/10) reported that > 20% of their minority pts have enrolled in clinical trials. Specialists agreed that minority pts experience barriers to participation in clinical research, including lack of trust in the healthcare system, materials in their native languages, financial support, minority investigators involved in clinical trials, and accessible study sites. The specialists proposed strategies that could be implemented to increase minority enrollment. These included study sites where minority populations live and industry funded outreach and educational efforts in minority communities. If sites are more accessible, this can reduce time and financial pressures associated with study participation. The specialists recommended that studies be designed to be more supportive of minority populations, specifically regarding inclusion and exclusion criteria and reimbursement of costs. They also advised that increased diversity among clinical researchers and allied personnel may increase the ability of the clinical team to connect with pts and assist in building trust in their communities. Finally, they emphasized the importance of providing informed consent forms and study materials in pts’ native languages. Conclusions: While challenges exist to increasing diversity in oncology clinical studies, a broad consortium of clinical specialists agreed that they can be addressed by community outreach and education, making study sites more accessible, availability of study materials in pts’ native languages, and improving diversity of clinical teams.

7002 Background: ZUMA-3 is a Phase 1/2 multicenter study evaluating KTE-X19, an autologous anti-CD19 CAR T-cell therapy, in adult pts with R/R B-ALL. Phase 1 efficacy results at the recommended Phase 2 dose (1×106 CAR T cells/kg) were encouraging (Shah et al. ASCO 2019 #7006). Here, we present the pivotal Phase 2 results. Methods: Eligible adults had R/R B-ALL, > 5% bone marrow (BM) blasts by local evaluation, and ECOG 0–1. Pts received a single infusion of KTE-X19 after conditioning chemotherapy. The primary endpoint was the overall complete remission (CR) rate (CR + CR with incomplete hematologic recovery [CRi]) by central review. Key secondary endpoints were duration of remission (DOR), relapse-free survival (RFS), overall survival (OS), measurable residual disease negativity (MRD–) rate by flow cytometry, and safety. Data are reported in all treated pts. Results: As of 9/2020, 55 of 71 enrolled pts received KTE-X19, with a median follow-up of 16.4 mo (range, 10.3–22.1). Adverse events (AEs; n = 8) and ineligibility (n = 4) were the most common reasons enrolled pts did not receive KTE-X19 infusion. Median age was 40 y (range, 19–84), median BM blasts at screening were 65% (range, 5–100), and 47% of pts had ≥3 prior therapies, with 45%, 22%, and 42% having previously received blinatumomab, inotuzumab ozogamicin, or allogeneic stem cell transplant (alloSCT), respectively. The CR/CRi rate was 71% (95% CI, 57–82; 56% CR, 15% CRi); 31% of responders had ongoing responses. Median (95% CI) DOR, RFS, and OS were 12.8 mo (8.7–not estimable [NE]), 11.6 mo (2.7–15.5), and 18.2 mo (15.9–NE), respectively. In responders, median (95% CI) RFS and OS were 14.2 mo (11.6–NE) and not reached (16.2–NE). The MRD– rate was 97% among pts with CR/CRi. Among 25 pts with prior blinatumomab treatment, the CR/CRi rate was 60%. Ten pts (18%) received subsequent alloSCT at a median 98 days post–KTE-X19 infusion. Median DOR remained unchanged when not censoring for alloSCT. Grade ≥3 AEs occurred in 95% of pts, most commonly anemia (49%) and neutropenia (49% [febrile 13%]). Grade ≥3 cytokine release syndrome (CRS; per Lee at al. Blood 2014) and neurologic events occurred in 24% and 25% of pts, respectively, and were generally reversible. Two Grade 5 KTE-X19–related events occurred (brain herniation, n = 1; septic shock, n = 1). Median times to onset of CRS and neurologic events were 5 d and 9 d, with median durations of 7.5 d and 7 d, respectively. Median peak CAR T-cell levels (cells/µL) were 40.5 (range, 1.3–1533.4) in pts with CR and 0 in nonresponders. CAR T cells were undetectable by 9 mo in ongoing responders. Conclusions: After a median follow-up of 16.4 mo, KTE-X19 demonstrated compelling clinical benefit in heavily pretreated adults with R/R B-ALL, with the median OS not yet reached for responding pts and a manageable safety profile. Clinical trial information: NCT02614066.

5001 Background: Tak is an oral selective nonsteroidal 17, 20-lyase inhibitor that blocks the synthesis of gonadal and adrenal androgens. We evaluated the clinical benefit of Tak with ADT in pts with newly diagnosed mHSPC. Methods: Pts with mHSPC with a Zubrod performance status (PS) of 0-2 and a PSA of ≥ 2 ng/ml were randomized 1:1 to ADT+Tak (300 mg twice daily) or ADT+Bic (50 mg daily). Stratification factors included PS (0-1 vs ≥2), extent of disease (minimal vs extensive), and receipt of ADT prior to registration (yes vs no). The primary endpoint was overall survival (OS). Secondary endpoints were progression free survival (PFS; based on PSA, imaging or clinical progression), PSA at 7 months (≤0.2 vs 0.2 < PSA; ≤-4 vs. > 4 ng/ml) and adverse event (AE) profile. With 2.75 yrs to accrue 1,186 eligible pts and 3 additional yrs of follow-up, we would have 90% power to determine a 33% improvement in OS from 54 to 72 mos (1-sided α = 0.025). A final analysis was pre-specified after 523 deaths using a 1-sided α = 0.022 to account for interim analyses. Results: Between 3/2013 and 7/2017, 1,313 pts were randomized and 1,279 were included in the intention-to-treat (ITT) analysis (32 pts were ineligible and 2 pts withdrew consent). Median age was 68 yrs and 10% of subjects were Black. Median PSA was 30 ng/mL (range 2-6710) and 49% of pts had extensive disease. After a median follow-up of 4.9 yrs, PFS and PSA response were significantly improved with Tak over Bic but no significant improvement in OS was observed (Table). More grade 3/4 AEs occurred in Tak vs. Bic arms (43% vs. 14%), and included hypertension (20% vs. 5%) and fatigue (5% vs. 2%). Five pts in Tak and 1 pt in the Bic arm had grade 5 AE. Conclusions: Despite clinically meaningful improvement in various outcome measures with Tak+ADT over Bic+ADT in this representative population of mHSPC, the improvement in OS did not meet the pre-specified criteria for statistical significance. The median OS of 70 mos in the control arm (standard ADT) was higher than that reported in contemporary phase 3 trials in this setting, and 16 mos higher than originally estimated. This trial sets a new landmark for survival estimates when pts with mHSPC have access to multiple approved subsequent life-prolonging therapies. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819, U10CA180820; U10CA180821; and in part by Millennium Pharmaceuticals, Inc. (Takeda Pharmaceutical Company LTD) Clinical trial information: NCT01809691. [Table: see text]

Objectives We evaluated the outcomes of metastatic pancreatic cancer (MPC) patients who underwent liver metastases (LMs)–directed ablative radiotherapy (RT) and sought to characterize patients with more favorable prognosis. Methods A retrospective analysis of 76 MPC patients who underwent ablative RT (median dose, 50 Gy) to LM at 3 academic centers between 2008 and 2018 was performed. Endpoints were local control (LC), progression-free survival, and overall survival (OS) since RT. Results Median follow-up was 10.9 months. Liver metastases were metachronous in 68%. Before RT, LM was responsive/stable on chemotherapy (CTX) in 36% whereas progressive in 43%. Median carbohydrate antigen 19-9 (CA 19-9) at RT was 334 U/mL. After RT, 32% had ≥6 months of CTX break. Twelve-month outcomes were: LC, 66%; progression-free survival, 7%; and OS, 38%. On multivariable analysis, Eastern Cooperative Oncology Group 2–3 (hazard ratio [HR], 13.49; P < 0.01), progressive LM on CTX (HR, 3.26; P < 0.01), and higher CA 19-9 (log 10 scale; HR, 1.39; P < 0.01) at RT predicted worse OS. Conclusions Ablative RT to LM in setting of MPC may offer LC of systemic disease and thus quality time off CTX. Selected patients with good performance status, stable/responsive LM on CTX, and lower CA 19-9 have more favorable prognosis.

BACKGROUND Aging of the face and upper neck is a complex process characterized by loss of collagen and elastic fibers, resulting in clinical skin laxity. Noninvasive interventions such as monopolar capacitively coupled radiofrequency (MRF) have gained popularity, offering a safer and more convenient alternative to traditional surgical face lift. The latest MRF device features larger tips, vibration, cooling, and impedance matching. OBJECTIVE We performed the first open-label clinical trial, measuring the efficacy, safety, and patient satisfaction of this device for noninvasive lifting and tightening of the face and upper neck. MATERIALS AND METHODS Forty subjects 30 to 60 years of age with mild/moderate skin laxity of the face and upper neck were enrolled. After pretreatment with ketorolac 60 mg intramuscular injection, subjects underwent treatment with MRF. Follow-up evaluations were performed on Days 30, 60, and 180. RESULTS Our study demonstrated that the newest generation MRF produced statistically significant improvement in skin laxity 6 months post-treatment, especially in the jowls and melolabial folds. According to the Investigator Global Aesthetic Improvement Score, 73% of subjects had improvement at 6 months post-treatment. Subject satisfaction and improvement questionnaires supported these findings. CONCLUSION Our data coupled with the excellent adverse effect profile validates MRF as an attractive treatment modality for facial and upper neck skin laxity.

AbstractAims and ObjectivesTo determine the level of convergent validity of the ‘6‐Clicks’ Basic Mobility and Daily Activity with the Bedside Mobility Assessment Tool (BMAT) in patients admitted to a tertiary care academic hospital.BackgroundAccurately measuring a patient's ability to mobilise during hospitalisation is necessary but can be challenging. Two instruments, the Activity Measure for Post‐Acute Care short‐form ‘6‐Clicks’ and the BMAT, are commonly used to determine patients’ mobility levels; however, these instruments have not been psychometrically evaluated together. Understanding the characteristics between these tools can support the process of shared decision making amongst healthcare providers.DesignRetrospective Cohort adhering to the STROBE statement.MethodsUsing 13,498 individual patient admissions from an electronic health record, the BMAT score measured closest in time to the ‘6‐Clicks’ Basic Mobility and Daily Activity evaluation was collected. Spearman rank correlations with 95% confidence intervals (CIs) were calculated to determine the level of convergent validity between the ‘6‐Clicks’ Basic Mobility and Daily Activity with the BMAT. Pairwise correlations were also calculated and stratified by admitting medical service.ResultsAll correlations for the ‘6‐Clicks’ Basic Mobility or Daily Activity summative scores and the BMAT mobility levels were statistically significant and moderately correlated. The weakest correlations were seen within the Orthopaedic admitting service group. Most correlations stratified by admitting service [CVD/Pulmonary, Medicine/Hospitalist, Other Surgery and Solid Organ Transplant] were moderate. The strongest correlations were seen within the Neuro/Stroke admitting service.ConclusionModerate levels of convergent validity exist between the ‘6‐Clicks’ and the BMAT in this sample. These findings demonstrate that the construct of patient mobility is not being assessed similarly between the two instruments.Relevance to Clinical PracticeThese findings suggest the continued use of both instruments to allow interdisciplinary assessment of patient mobility status during a hospital stay.

Abstract ZUMA-3 is a phase 1/2 study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We report the phase 1 results. After fludarabine-cyclophosphamide lymphodepletion, patients received a single infusion of KTE-X19 at 2 × 106, 1 × 106, or 0.5 × 106 cells per kg. The rate of dose-limiting toxicities (DLTs) within 28 days after KTE-X19 infusion was the primary end point. KTE-X19 was manufactured for 54 enrolled patients and administered to 45 (median age, 46 years; range, 18-77 years). No DLTs occurred in the DLT-evaluable cohort. Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 31% and 38% of patients, respectively. To optimize the risk-benefit ratio, revised adverse event (AE) management for CRS and NEs (earlier steroid use for NEs and tocilizumab only for CRS) was evaluated at 1 × 106 cells per kg KTE-X19. In the 9 patients treated under revised AE management, 33% had grade 3 CRS and 11% had grade 3 NEs, with no grade 4 or 5 NEs. The overall complete remission rate correlated with CAR T-cell expansion and was 83% in patients treated with 1 × 106 cells per kg and 69% in all patients. Minimal residual disease was undetectable in all responding patients. At a median follow-up of 22.1 months (range, 7.1-36.1 months), the median duration of remission was 17.6 months (95% confidence interval [CI], 5.8-17.6 months) in patients treated with 1 × 106 cells per kg and 14.5 months (95% CI, 5.8-18.1 months) in all patients. KTE-X19 treatment provided a high response rate and tolerable safety in adults with R/R B-ALL. Phase 2 is ongoing at 1 × 106 cells per kg with revised AE management. This trial is registered at www.clinicaltrials.gov as #NCT02614066.