bluuebunny/crossref_metadata_2025 huggingface dataset:
A multilevel intervention increased accrual of Native Hawaiians and other Pacific Islanders to a national breast cancer screening trial.
Authors: Wakuk Srue , Berenberg Jeffrey L. , Capps Erin , Morris Paul , Cheng Shirley , Bryant-Greenwood Kate , Cassel Kevin
Published: June 2022

6547

Background: The University of Hawaii Cancer Center (UHCC) Minority/Underserved NCI Community Oncology Research Program (Hawaii MU NCORP) provides access to NCI-sponsored clinical trials in Hawaii. The Hawaii MU NCORP is dedicated to increasing minority and underserved accruals to clinical trials. Native Hawaiian women have the highest breast cancer incidence and mortality; only 26% of Micronesian women in Hawaii over the age of 40 have ever had a mammogram. In 2018, the Hawaii MU NCORP became a recruitment site for the ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST). A pilot study was launched in 2019, to support our NCORP recruitment of underrepresented Native Hawaiian and other Pacific Islander (NHPI) women to the TMIST study. Subsequently, specific funding was provided by the NCI’s Center to Reduce Cancer Health Disparities that enabled the UHCC’s Office of Community Outreach and Engagement (COE) to develop an effective multilevel recruitment strategy together with the Hawaii MIU NCORP. Methods: To foster community awareness of the TMIST study among NHPI women, the UHCC COE hired a Community Health Educator (CHE). The CHE, a Pacific Islander woman, utilized small group educational sessions to provide culturally and linguistically appropriate cancer prevention information and promote the TMIST study to NHPI women in Hawaii. The CHE worked in partnership with Hawaii MU NCORP clinical research associates (CRAs) in these efforts. In 2020, statewide COVID-19 health and safety protocols were enacted, limiting public group interactions in Hawaii. Despite this challenge, the CHE successfully adapted the in-person educational sessions on clinical trials and TMIST to conduct sessions using Zoom and Facebook Messenger. Results: Before the hire of the CHE in 2019, only one Pacific Islander (Micronesian) woman was recruited to the TMIST in Hawaii. The CHE conducted 21 community health events with 426 attendees from 2019 to 2021. The Hawaii MU NCORP NHPI TMIST enrollment went from the 9.9% in 2018 to 2019, to 20.1% in 2019 to 2020 and to 33% in 2020 to 2021. To date, 18 Micronesian, 52 Native Hawaiian and 6 Other Pacific Islander women out of 353 participants ware enrolled. Conclusions: The multilevel intervention of our CHE, in collaboration with NCORP staff providing clinical trial awareness training and community outreach, resulted in increasing the enrollment of NHPI women to the TMIST Trial. CHE-led community health education sessions on cancer prevention can be delivered using emergent technologies and social media. The use of culturally and gender concordant CHEs working with CRAs have the potential to increase awareness and accruals to cancer clinical trials.
Variation of use of targeted therapies and molecular diagnostic testing by practice type for non-small cell lung cancer and colorectal cancer.
Authors: Roberts Thomas , Kehl Kenneth L. , Brooks Gabriel A. , Sholl Lynette M. , Wright Alexi A. , Bai Barbara , Landrum Mary Beth , Keating Nancy Lynn
Published: June 2022

6551

Background: Targeted therapies are important first-line treatments for many patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). All patients with newly-diagnosed metastatic NSCLC and CRC should undergo molecular diagnostic testing to guide treatment selection. Methods: We used 100% Medicare fee-for-service data from 2015 through 2019 to identify beneficiaries with incident metastatic NSCLC or CRC receiving systemic therapy and to assign beneficiaries to oncology practices. We then assessed for use of molecular diagnostic testing and targeted therapies in these cohorts. We used linear mixed effects models to assess patient and practice characteristics associated with molecular diagnostic testing and targeted therapy use. Results: Rates of molecular diagnostic testing increased between 2015 and 2019 for NSCLC and CRC. In 2019, rates of molecular diagnostic testing were 85% and 65% for NSCLC and CRC, respectively. Rates of targeted therapy use did not increase over time for NSCLC or CRC, and were 8% and 5%, respectively, in 2019. Compared to National Cancer Institute (NCI)-designated cancer centers, rates of molecular diagnostic testing for CRC were 3.7 percentage points lower at practices associated with non-academic hospitals and 10.6 percentage points lower at small independent practices. Rates of targeted therapy use for NSCLC were 4.8, 5.9 and 5.5 percentage points lower at academic medical centers, large independent practices and small independent practices, respectively, compared to NCI centers. Conclusions: Rates of molecular diagnostic testing for NSCLC and CRC increased in recent years, but testing rates remain below recommended levels, and targeted therapy use remains low. Substantial variation in testing and targeted therapy use by practice type suggest that the practice where a patient is treated may impact access to recommended testing and efficacious treatments. [Table: see text]
Reducing oncology readmissions through a multidisciplinary discharge approach.
Authors: DiBenedetto Samantha , Pierce Eric , Wells Leah , Keng Michael Kenneth
Published: June 2022

6561

Background: Hospital readmissions are associated with increased health care utilization and unfavorable patient outcomes. Oncology patients have an increased risk of hospital readmission compared to the general patient population. The 30-day readmission rate for cancer patients at our institution is 27.7% which is higher than the reported national average of 20.2%. We sought to reduce 30-day hospital readmission rates by 25% for solid tumor oncology patients through a prospective integrated multidisciplinary discharge approach. Methods: Hospital readmissions for adult patients with a known solid tumor cancer diagnosis admitted to the oncology service at UVA from Jan 2019 – Apr 2019 were identified. Baseline information on tumor type, reason for readmission, interventions, length of stay (LOS), and inpatient morbidity and mortality (including ICU admission and transition to hospice) were collected via retrospective review. Qualitative and quantitative tools including process maps, cause-and-effect diagrams, Pareto charts, and priority matrix were used to identify potential areas for intervention. Two PDSA cycles were implemented: daily multidisciplinary discharge rounds with physicians, nursing, social work, case management, and PT/OT (PDSA1), and a templated discharge email to patients’ primary oncology team including attending oncologist, mid-level providers, nurse coordinator, pharmacist, and urgent care team (PDSA2). An SPC chart with 3-σ limits and t-test of unequal variance with 2-sided p-value was used to evaluate impact on readmission rates from baseline to PDSA2. Results: Following PDSA1 (May 2019 – Oct 2019), the 30-day readmission was 25.7%; PDSA2 was postponed due to COVID-19, however the 30-day readmission rate remained stable during the pandemic. Following PDSA2 (Sept 2021 – Dec 2021), the 30-day readmission rate was 18.2% corresponding to an absolute decrease of 34.3% which was statistically significant (p≤0.05). This was associated with a trend towards increased LOS, rate of ICU admission, and case-mix severity index although not statistically significant. There was no significant difference in inpatient mortality or transition to hospice (Table). Conclusions: Implementation of multidisciplinary discharge rounds and templated discharge communication resulted in a significant decrease in rate of 30-day readmissions for solid tumor oncology patients. There was a trend towards increased LOS and ICU admissions without increased inpatient mortality. Improvement in discharge email compliance and implementation of an urgent symptom clinic may further reduce the 30-day readmission rate. [Table: see text]
Implementing proven methods in a community-based health system to improve breast cancer screening rates during the COVID-19 pandemic.
Authors: Fadel Celine , Danak Shivang , Caton Andria P
Published: June 2022

6565

Background: There are reduced screening rates across the United States secondary to the COVID-19 pandemic; the additional anticipated deaths from breast and colorectal cancer, secondary to reduced screening, is approximated at 10,000 people. A study of thirty-two health systems in Georgia noted an 8% decrease in screening mammography compared to pre-pandemic rates. To help reverse the decline, Northeast Georgia Medical Center (NGMC) participated in the "Return to Screening" initiative, in conjunction with the American Cancer Society (ACS). A quality improvement project was performed at the community-based hospital system to increase breast cancer screening rates, using a multidisciplinary approach with a focus on health care disparities. Methods: The initial goal was to increase screening mammograms by 10% (n = 14,364) from June 1st to December 1st 2021. Interventions were selected by a multidisciplinary team of NGMC researchers, clinical providers, and oncology administrators. Interventions varied in category, encompassing unique patient and provider-specific approaches. The evidence-based interventions were tailored to address health care disparities in the local population. This included identification and quantification of cultural groups in the community to ensure quality patient access. Integrative collaboration consisted of intermittent meetings to certify consistent communication, project reflection and identification of barriers. The selected interventions were executed monthly, with simultaneous data tracking of mammography rates. Results: From June 1st to December 1st 2021, a total of forty evidence-based interventions were successfully implemented. Analysis of screening rates demonstrated a 15% increase across the allotted time period, corresponding to an average of 1,302 mammograms monthly (n = 15,284). This exceeded the initial anticipated goal of increasing screening by 10% (n = 14,364). Analysis of mammography results identified 331 new cases of breast cancer diagnosed within the allotted period, a 7% mean diagnosis rate increase. Certain planned interventions were unable to be conducted and required modification due to limitation of the ongoing pandemic; however, this solidified the use of social media and virtual participation as effective methods of community outreach. Conclusions: We identified key methods to engage the local community and successfully increased rates of screening mammography. Interventions were tailored to the local population, ensuring patient-centered tools and a personalized approach to medicine. The multidisciplinary, consistent collaboration with stakeholders ensured quality of care for the local patient population. This project demonstrates the importance of local community engagement to impact national cancer screening rates, and thus, ensure earlier detection of breast cancer.
Overall survival (OS) of patients with TRK fusion–positive cancer receiving larotrectinib versus standard of care (SoC): A matching-adjusted indirect comparison (MAIC) using real-world data (RWD).
Authors: Bokemeyer Carsten , Paracha Noman , Lassen Ulrik Niels , Italiano Antoine , Sullivan Sean D , Marian Marisca , Fellous Marc Mardoche , García-Foncillas Jesús
Published: June 2022

6579

Background: Larotrectinib trials in Tropomyosin Receptor Kinase (TRK) fusion cancer population were single arm trials and therefore limited comparative effectiveness data with larotrectinib are available.MAIC is typically used to balance population characteristics to facilitate cross-study comparisons. The objective of this study was to use MAIC to compare efficacy of the highly specific TRK inhibitor larotrectinib vs. SoC. Methods: Individual patient data from larotrectinib trials (NCT02122913, NCT02637687, NCT02576431) were compared with published aggregate SoC data from patients with locally advanced/metastatic TRK fusion cancer identified in the Flatiron Health/Foundation Medicine clinico-genomic database (Demetri et al. Ann Oncol. 2021). Prior to matching, eligible patients were ≥18 years and had to have received ≤4 lines of prior therapy (LoPT). Patients were matched on available common baseline characteristics (Table). Overall survival was the only endpoint assessed and was defined as time from locally advanced/metastatic disease diagnosis to death. The analyses included: 1) a log-rank test of equality to test whether the two groups were similar before larotrectinib initiation; and 2) estimation of treatment effect of larotrectinib vs. SoC. Hazard ratios (HRs) were used to compare the 2 groups. MAIC assumes that all observed and unobserved prognostic factors are adjusted for in the analysis. Results: 85 larotrectinib patients and 28 SoC patients were included. After matching, log-rank testing suggested no difference between the 2 groups (P=0.26), and larotrectinib was associated with a 78% lower risk of death (adjusted HR: 0.22 [95% confidence interval: 0.09, 0.54]; P=0.001), compared to SoC. Conclusions: This analysis suggests longer overall survival with larotrectinib, compared to SoC, in adult patients with TRK fusion cancer. The current analysis was limited to the prognostic variables available in the RWD. Further data are warranted to confirm those results. [Table: see text]
Frailty status derived from the electronic medical record to predict survival and health care utilization in veterans with lung and gastrointestinal cancers.
Authors: Yarlagadda Sudha , Razjouyan Javad , Naik Aanand , Sada Yvonne
Published: June 2022

6582

Background: Frailty is associated with increased vulnerability to stressors. Although frailty is a predictor of survival, traditional frailty assessments are not feasible in clinical practice. Frailty indexes (FI) derived from the electronic medical record (EMR) are an alternate approach. There is limited data for the association between EMR-FI and cancer-related outcomes including survival and health care utilization. Methods: We identified a cohort of patients diagnosed with lung or gastrointestinal cancer from 2016-2020 using VA administrative files. We used the Veterans Affairs-FI (VA-FI), a validated 31-item cumulative deficit FI, to define three groups: robust (≤0.1), prefrail (0.1-0.2), frail ( > 0.2). Cox proportional hazard analyses were conducted to evaluate survival. Logistic regression analyses were performed to examine healthcare utilization. All models were adjusted for age, gender, race, Charlson comorbidity index, and stage. Results: Among 37,439 patients (age: 70±8.6 years), the majority were prefrail (36.8%) or frail (24.1%). Prefrail patients had a 13% increased risk of death compared to robust patients (adjusted hazard ratio [aHR] 1.13; 95% CI 1.10-1.16), while frail patients had a 52% increased risk (aHR 1.52; 95% CI 1.47, 1.57). Pre-frail and frail patients had increased odds of 1-year ED visits (adjusted odds ratio [aOR] 1.33; 95% CI 1.27 - 1.40 and aOR, 1.88, 95% CI 1.77-2.00, respectively). Frailty status was associated with increased odds of 1-year all-cause hospitalization among prefrail (aOR 1.09; 95% CI 1.03-1.15) and frail patients (aOR 1.26; 95%CI: 1.18, 1.34). Conclusions: Frailty measured by EMR data is significantly associated with survival and healthcare utilization among patients with lung and gastrointestinal cancers, independent of stage. Further study is warranted to develop EMR-FI as a risk stratification tool for personalized cancer treatment decisions.
Price variability of pembrolizumab in New York City from 2016-2021.
Authors: Hussaini Syed , Johnson Jordan , Chino Fumiko
Published: June 2022

6601

Background: There is poor compliance among cancer centers with price transparency rules set forth by the CMS in 2021. Service charges higher than what a hospital reasonably expects to be reimbursed may both prevent competitive price shopping by the consumer and result in catastrophic financial toxicity for small payors and under/uninsured individuals. We investigated variability in the charged and reimbursed payments for pembrolizumab infusion within one metro area utilizing Medicare claims. Methods: Medicare claims data from 2016 through 2021 for all pembrolizumab (HCPCS J9271) infusions in a hospital outpatient department were selected from the Definitive Healthcare claims database for medical oncology providers in New York City (NYC). Average charges, reimbursements, and total claims were obtained for the 6 largest prescribers by volume. Annual percentage changes (APC) were calculated to evaluate trends during study period. Prices are presented as inflation adjusted numbers (charged and reimbursed; 2021 dollars). Analyses were performed in Excel (Microsoft Corp). Results: Our analysis included 5 NCI-designated cancer centers (NCI-A, NCI-B, NCI-C, NCI-D) of which 1 was PPS (Prospective Payment System)-exempt (NCI-PPS). One hospital was non-NCI and 4 hospitals were part of the discounted 340B Drug Pricing Program (NCI-A, NCI-B, NCI-D, Non-NCI). From 2016 to 2021, total Medicare claims increased 793 to 1537, and total payments to all centers increased from $5.4M to $16.3M. NCI-PPS comprised 61% of claims, and 65% of total payments in 2021. Average charge for pembrolizumab in 2021 ranged from $20,130 (NCI-PPS) to $155,825 (NCI-D/340B). During study period, APC ranged from +1.7% (NCI-A/340B) to +25.4% (NCI-D/340B). Despite wide variability in charged amounts for Medicare claims, re-imbursed amounts were similar across centers (range: $6227-9623, 2021). Conclusions: There is significant variability in charges for pembrolizumab in Medicare claims with price increases outpacing the annual rate of inflation. Within NYC, the highest charges were from a 340B hospital; NCI-PPS had higher volume and total payments but consistently lower charged prices each year. Our study highlights extreme price variability, and has policy implications for price transparency requirements and uniform rate setting to establish payment levels and control rate of annual growth. [Table: see text]
MOMENTUM: Phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor.
Authors: Mesa Ruben A. , Gerds Aaron Thomas , Vannucchi Alessandro , Al-Ali Haifa Kathrin , Lavie David , Kuykendall Andrew T. , Grosicki Sebastian , Iurlo Alessandra , Goh Yeow Tee , Lazaroiu Mihaela Cornelia , Egyed Miklos , Fox Maria Laura , McLornan Donal P. , Perkins Andrew , Yoon Sung-Soo , Gupta Vikas , Kiladjian Jean-Jacques , Donahue Rafe , Kawashima Jun , Verstovsek Srdan
Published: June 2022

7002

Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity on MF symptoms, RBC transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials. This pivotal phase 3 study of MF patients (pts) previously treated with a JAK inhibitor (JAKi) tested MMB vs DAN on key symptom, anemia, and spleen volume endpoints at 24 weeks (wks). Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; Hgb <10 g/dL; prior JAKi for ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 wks or Gr 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm. Stratification: TSS, palpable spleen, and RBC units transfused. JAKi taper and washout was ≥21 days. Randomization: 2:1 to MMB 200 mg QD plus DAN placebo or DAN 600 mg QD plus MMB placebo for 24 wks, after which pts could receive open-label MMB. Assessments: Pt reported symptoms using a daily eDiary and spleen volume by MRI or CT. The primary endpoint was TSS response (≥50% reduction from baseline [BL]) rate at wk 24. Secondary endpoints, assessed sequentially at wk 24, were RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from BL), change from BL in TSS, SRR (≥35% reduction from BL) and rate of zero transfusions since BL. Results: 94 of 130 (72%) MMB pts and 38 of 65 (58%) DAN pts completed the 24-wk randomized treatment (RT) phase. Median BL TSS were 28 (MMB) and 26 (DAN), Hgb were 8.1 (MMB) and 7.9 (DAN) g/dL, and platelets were 97 (MMB) and 94 (DAN) x109/L. BL TI was 13% (MMB) and 15% (DAN). Prior JAKi was ruxolitinib in 195 pts (100%) and fedratinib in 9 pts (5%). All primary and key secondary endpoints were met (Table). Most common Gr ≥3 TEAEs in the RT phase of the study were thrombocytopenia (MMB, 22%; DAN, 12%) and anemia (MMB, 8%; DAN, 11%). Gr ≥3 infections occurred in 15% of MMB and 17% of DAN pts. Peripheral neuropathy occurred in 5 (4%) of MMB (all Gr ≤2) and 1 (2%) of DAN (Gr ≤2) pts in the RT phase, and none discontinued study drug. Overall, TEAEs led to study drug discontinuation in 18% of MMB and 23% of DAN pts in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN (HR=0.506, p=0.0719). Conclusions: In symptomatic and anemic MF pts, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need, particularly in MF pts with anemia. Clinical trial information: NCT04173494. [Table: see text]
V-FAST master trial: Preliminary results of treatment with CPX-351 plus midostaurin in adults with newly diagnosed FLT3-mutated acute myeloid leukemia.
Authors: McCloskey James K. , Pullarkat Vinod A. , Mannis Gabriel N. , Lin Tara L. , Strickland Stephen Anthony , Fathi Amir Tahmasb , Erba Harry Paul , Faderl Stefan , Chakravarthy Divya , Lutska Yana , Chandrasekaran Vijayalakshmi , Cheung Ronald , Levis Mark J.
Published: June 2022

7043

Background: CPX-351 (US: Vyxeos; Europe: Vyxeos liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved for newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes in patients aged ≥1 year in the US and in adults in Europe. In a phase 3 study in older adults with newly diagnosed, high-risk/secondary AML, CPX-351 significantly improved overall survival and remission rates versus conventional 7+3, with a comparable safety profile. Preclinical data suggest CPX-351 may have synergistic activity with targeted agents, including the FLT3 inhibitor midostaurin (MID). Herein, we report preliminary results for the cohort of adults treated with CPX-351 + MID in the V-FAST (Vyxeos – First Phase Assessment with Targeted Agents) trial. Methods: V-FAST is an open-label, multicenter, multiarm, nonrandomized, phase 1b master trial (NCT04075747) to evaluate the safety and preliminary efficacy of CPX-351 combined with targeted agents (midostaurin, venetoclax, enasidenib). Eligible adults in the CPX-351 + MID cohort were aged 18 to 75 years, had newly diagnosed AML with a FLT3 internal tandem duplication (ITD) or tyrosine kinase domain (TKD) mutation, were fit for intensive chemotherapy, and had an ECOG performance status of 0 to 2. The dose-exploration phase (3+3 design) determined a recommended phase 2 dose of CPX-351 100 units/m2 (daunorubicin 44 mg/m2 + cytarabine 100 mg/m2) on Days 1, 3, and 5 + MID 50 mg BID on Days 8 to 21. There were no dose-limiting toxicities, and additional patients were enrolled in the expansion phase at this dose. Results: A total of 23 patients received CPX-351 + MID and had sufficient data to be included in the analysis (cutoff date: 1/20/2022). Patient baseline characteristics are shown in the Table. Treatment-emergent adverse events (TEAEs) in ≥40% of patients included febrile neutropenia (78%), nausea (65%), increased alanine aminotransferase (57%), leukopenia (57%), thrombocytopenia (57%), headache (43%), and hyponatremia (43%). All patients experienced a grade 3/4 TEAE, primarily hematologic events. Nonhematologic grade 3/4 TEAEs in ≥2 patients included pneumonia (17%), lung infection (13%), and hyperglycemia (9%). There were no grade 5 TEAEs and no deaths on or before Day 60. Complete remission was achieved by 18/22 (82%) evaluable patients after the first induction cycle. Conclusions: Preliminary results from the V-FAST trial suggest CPX-351 + MID is feasible, with a manageable safety profile and promising remission rates in adults with newly diagnosed AML who have a FLT3 mutation. Clinical trial information: NCT04075747. [Table: see text]
ASPEN: Long-term follow-up results of a phase 3 randomized trial of zanubrutinib (ZANU) versus ibrutinib (IBR) in patients with Waldenström macroglobulinemia (WM).
Authors: Tam Constantine Si Lun , Garcia-Sanz Ramón , Opat Stephen , D'Sa Shirley , Jurczak Wojciech , Lee Hui-Peng , Cull Gavin , Owen Roger G. , Marlton Paula , Wahlin Bjorn E. , Tedeschi Alessandra , Castillo Jorge J. , Siddiqi Tanya , Buske Christian , Leblond Veronique , Chan Wai Y. , Schneider Jingjing , Cohen Aileen , Huang Jane , Dimopoulos Meletios A.
Published: June 2022

7521

Background: ASPEN is a randomized, open-label, phase 3 study comparing ZANU, a potent and selective Bruton tyrosine kinase inhibitor (BTKi), with the first-generation BTKi IBR in patients with WM. We present data with a median follow-up of 43 months. Methods: Patients with MYD88 mutations were assigned to cohort 1 and randomized 1:1 to receive ZANU 160 mg twice daily or IBR 420 mg once daily. Randomization was stratified by CXCR4 mutational status and lines of prior therapy (0 vs 1-3 vs > 3). Patients without MYD88 mutations were assigned to cohort 2 and received ZANU 160 mg twice daily. The primary endpoint was proportion of patients achieving complete response or very good partial response (CR+VGPR). Results: A total of 201 patients (ZANU arm, n = 102; IBR arm, n = 99) were enrolled in cohort 1 and 28 patients were enrolled in cohort 2. A larger proportion of patients in the ZANU arm of cohort 1 vs IBR had CXCR4 mutations by next-generation sequencing (32% vs 20%, or 33 of 98 vs 20 of 92 with data available) and were aged > 75 years (33% vs 22%). Median duration of treatment was 42 months (ZANU) and 41 months (IBR), with 67% and 58% remaining on treatment, respectively. The CR+VGPR rate by investigator was 36% with ZANU vs 22% with IBR ( p= 0.02) in cohort 1, and 31% in cohort 2. One patient achieved CR (cohort 2). In patients with wild type or mutant CXCR4 from cohort 1, CR+VGPR rates with ZANU vs IBR were 45% vs 28% ( p= 0.04) and 21% vs 5% ( p= 0.15) , respectively. Median progression-free survival and overall survival were not yet reached. Rates of atrial fibrillation, diarrhea, hypertension, localized infection, hemorrhage, muscle spasms, pneumonia, and adverse events leading to discontinuation or death were lower with ZANU vs IBR (Table). Exposure-adjusted incidence rates of atrial fibrillation/flutter and hypertension were lower with ZANU vs IBR (0.2 vs 0.8 and 0.5 vs 1.0 persons per 100 person-months, respectively; p< 0.05). Rate of neutropenia was higher and rate of grade ≥3 infection was lower with ZANU vs IBR. Safety outcomes of ZANU were similar between cohorts 1 and 2. Conclusions: ASPEN is the largest phase 3 trial with head-to-head BTKi comparison in WM. At a median follow-up of 43 months, ZANU was associated with higher CR+VGPR rate and demonstrated clinically meaningful advantages in long-term safety and tolerability vs IBR. Clinical trial information: NCT03053440. [Table: see text]
Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Five-year follow-up of ELEVATE-TN.
Authors: Sharman Jeff Porter , Egyed Miklos , Jurczak Wojciech , Skarbnik Alan P. , Kamdar Manali K. , Munir Talha , Fogliatto Laura , Herishanu Yair , Banerji Versha , Follows George , Walker Patricia , Karlsson Karin , Ghia Paolo , Janssens Ann , Ferrant Emmanuelle , Munugalavadla Veerendra , Yu Ting , Wang Min Hui , Woyach Jennifer Ann
Published: June 2022

7539

Background: For ELEVATE-TN (NCT02475681), we previously reported superior efficacy of acalabrutinib (A) ± obinutuzumab (O) vs O + chlorambucil (Clb) in patients (pts) with treatment-naive (TN) chronic lymphocytic leukemia (CLL) at 28.3 and 46.9 months (mo) median follow-up. Now, we report results from a 5-y update. Methods: Pts were randomized to A+O, A, or O+Clb. Pts who progressed on O+Clb could cross over to A monotherapy. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Results: A total of 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) had a median age of 70 y. At a median follow-up of 58.2 mo (range, 0.0–72.0; data cutoff Oct 1, 2021), median PFS was not reached (NR) (hazard ratio [HR]: 0.11) for A+O and A (HR: 0.21) vs 27.8 mo for O+Clb (both P<0.0001). Estimated 60-mo PFS rates were 84% (A+O), 72% (A), and 21% (O+Clb). Median OS was NR in any treatment arm, and significantly longer in the A+O vs O+Clb arms (HR: 0.55; P=0.0474); estimated 60-mo OS rates were 90% (A+O), 84% (A), and 82% (O+Clb). ORR was significantly higher with A+O (96%; 95% CI 92–98) and A (90%; 85–94) vs O+Clb (83%; 77–88; P<0.0001 [A+O], P=0.0499 [A]). Complete response (CR)/CR with incomplete hematologic recovery (CRi) rates were higher with A+O (29%/3%) vs O+Clb (13%/1%); 13%/1% had CR/CRi with A; CR increased since the interim analysis (previously 21% [A+O] and 7% [A]). Adverse events (AEs) and treatment exposure are shown in the Table. Treatment is ongoing in 65% (A+O) and 60% (A) of pts; the most common reasons for treatment discontinuation were AEs (17% [A+O], 16% [A], 14% [O+Clb]) and progressive disease (6%, 10%, 2%, respectively). Crossover from O+Clb to A occurred in 72 (41%) patients; 25% of these pts discontinued A (10% due to AEs and 11% due to progressive disease). Conclusions: After a 5-y follow-up, efficacy and safety of A+O and A monotherapy were maintained, with significantly longer OS in the A+O arm compared with O+Clb. Clinical trial information: NCT02475681. [Table: see text]
Racial and socioeconomic disparities among patients with chronic lymphocytic leukemia: Analysis of Surveillance, Epidemiology, and End Results program data.
Authors: Kittai Adam , Huang Ying , Fisher James L. , Bhat Seema , Grever Michael R. , Paskett Electra D. , Rogers Kerry Anne , Woyach Jennifer Ann
Published: June 2022

7542

Background: Therapy for chronic lymphocytic leukemia (CLL) has changed dramatically over the past 20 years. With the cost of new therapies and rapid practice changes, it is unclear if patients (pts) are benefiting equally from this progress. We assessed Surveillance, Epidemiology, and End Results (SEER) program data to determine how race and socioeconomic status (SES) affect survival for pts with CLL. Methods: CLL cases reported to 18 SEER Program registries from 2006 – 2018 were included. Pt characteristics such as age at diagnosis (dx), sex, year (yr) of dx, race, and SES as determined by rural/urban census tract residence (RUCA), and neighborhood (as represented by the Yost Index, a composite measure of 7 variables assessing different aspects of the SES of a census tract) were collected and analyzed. Multivariable cox regression (MVA) was used to determine adjusted odds of survival. Two separate databases were utilized, one which included data to 2018, and another which contained SES data but only had data available to 2016. Results: 46,605 cases from 2009 – 2018 were identified without SES data. The median age was 70 yrs, 60% were male, and there was an even distribution of patients diagnosed with CLL annually from 2009 – 2018. Of the cases with race reported, 89.9% were white, 7.3% Black, 2.4% Asian/Pacific islander, and 0.3% American Indian/Alaska Native. After a median follow up of 47 months, the median 3, 5, and 10 yr overall survival (OS) was 79.5%, 69.5%, and 48.8%, respectively. MVA showed Black race (HR 1.5, 95% CI 1.4 – 1.6) as the strongest independent prognostic variable for worse OS controlling for yr of dx, suggesting race was a significant factor in OS in the era of modern therapies. Using the linked RUCA and Yost tertiles for SES, 47,867 cases of CLL from 2006 – 2016 were analyzed. Median age, sex, and race distribution were similar to the prior analysis. MVA showed American Indian/Alaska Native, and Black race as independent prognostic variables for worse OS, and Yost group 2 and 3, representing higher SES, were found to be significant independent prognostic variables for improved OS (Table 1). In this analysis, race remained an independent variable for worse OS after controlling for SES. Conclusions: Black race and low SES are prognostic of OS in CLL. Further research is needed to determine whether this is due to access to therapy, quality of care, social determinants of heath, or disease biology.[Table: see text]
Quality-adjusted time without symptoms or toxicities (Q-TWiST) analysis of ZUMA-7, a randomized controlled trial of axicabtagene ciloleucel versus standard of care for second-line large B-cell lymphoma.
Authors: Kersten Marie José , Qiao Yao , Shah Ruchit , Solem Caitlyn , Snider Julia , To Christina Ann , Cheng Paul , Spooner Clare , Perales Miguel-Angel
Published: June 2022

7555

Background: Quality of life (QoL) post cancer therapy is increasingly important. We conducted a Q-TWiST analysis to compare the quality-adjusted survival of axicabtagene ciloleucel (axi-cel, a chimeric antigen receptor T-cell therapy) versus standard of care (SOC) among relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients enrolled in ZUMA-7 (NCT03391466), a Phase 3, randomized, open-label, multicenter study. ZUMA-7 met its primary endpoint of event-free survival; events were defined as death, progression, or new lymphoma therapy. Methods: Overall survival (OS) in the intention-to-treat (ITT) cohort was partitioned into 3 mutually exclusive health states as measured through a median follow-up duration of 23.5 months (m): time with grade 3/4 adverse events (AE) before an event (TOX); time without symptoms from events or toxicity (TWiST); and time after event (REL). Q-TWiST was calculated as the average time spent in each state, weighted by state-specific QoL utility (u, ranging from 0 to 1), assuming a base case u(TOX)=0.5, u(REL)=0.5, u(TWiST)=1. Threshold analyses assessed the mean Q-TWiST differences between axi-cel and SOC by varying u(TOX) and u(REL) from 0 to 1. Relative gains for axi-cel (axi-cel Q-TWIST gain divided by mean SOC OS) ≥15% were considered “clearly clinically important” using published norms. Nonparametric bootstrap 95% confidence intervals (CI) were computed. Subgroup analyses were performed for relapse status and age. Sensitivity analyses varying the follow-up duration from 3 to 37.7m were explored. Results: For the ITT cohort (n=359), mean time spent in TOX and TWiST was significantly longer for the axi-cel cohort compared to SOC, and mean time spent in REL was significantly shorter for axi-cel (Table). Using the base case, quality-adjusted survival was significantly longer for axi-cel by 3.7m, representing a 21.9% relative gain. In threshold analyses, the difference in Q-TWiST ranged from 1.2m (u(TOX)=0, u(REL)=1) to 6.2m (u(TOX)=1, u(REL)=0) in favor of axi-cel. Q-TWiST gains favored axi-cel across all subgroup analyses. Q-TWiST gains from axi-cel increased with longer follow-up. Conclusions: Axi-cel was associated with statistically significant and “clearly clinically important” gains in quality-adjusted OS vs. SOC in R/R LBCL, regardless of the relative decline in QoL associated with treatment toxicity, disease progression, or additional cancer treatment.[Table: see text]
Bendamustine rituximab (BR) versus ibrutinib (Ibr) as primary therapy for Waldenström macroglobulinemia (WM): An international collaborative study.
Authors: Abeykoon Jithma P. , Kumar Shaji , Castillo Jorge J. , D'Sa Shirley , Kastritis Efstathios , Durot Eric , Uppal Encarl , Morel Pierre , Paludo Jonas , Tawfiq Reema , Sarosiek Shayna , Ogunbiyi M Olabisi , Cornillet-Lefebvre Pascale , Kyle Robert A. , Delmer Alain , Gertz Morie A. , Dimopoulos Meletios A. , Treon Steven P. , Ansell Stephen M. , Kapoor Prashant
Published: June 2022

7566

Background: Parenteral limited-duration BR chemoimmunotherapy and continuous orally administered Ibr, a Bruton tyrosine kinase inhibitor, dominate the treatment landscape of WM, a rare B cell lymphoma. No trials have assessed the comparative effectiveness of these 2 vastly different approaches. We conducted a multiinstitutional, international, collaborative study to compare BR and single-agent Ibr in patients (pts) with treatment naïve (TN) WM. Methods: Data from 347 pts with active TN WM, seen between 2011 and 2021 in the US and Europe, were analyzed. The pts on rituximab maintenance were excluded. The modified IWWM-6 criteria (based on IgM alone) were used for response assessment. All time-to-event analyses were performed from the frontline therapy initiation, using the Kaplan-Meier method. Results: The median age of the pts treated with BR (n=208) and Ibr (n=139) was 66 (range 40-86) years (y) and 69 (39-97) y, respectively, (p=0.005). With a median follow up of 4.2 y (95% CI 3.8-4.5), the 4-y progression free survival (PFS) was 73% in each group, p=0.6, and 4-y overall survival (OS) was 94% (95% CI 91-98) in the BR group versus ( v) 82% (95% CI 75-90) in the Ibr group, p=0.01. In a bivariate analysis adjusting for age and the treatment type, only age emerged as a predictor for OS (HR 7.2, p=0.0001). Therefore, a 1:1 age-matched analysis of 246 pts who received Ibr (n=123) or BR (n=123) was performed. Pts with a known MYD88WT status who had received Ibr and their age matched controls on BR were excluded. The international prognostic scoring system (IPSS) WM was comparable between the 2 groups (Table). A higher proportion of pts on BR attained very good partial or deeper response (≥VGPR) as the best response in comparison to the pts on Ibr (Table). The 4-y PFS for the BR and Ibr groups was similar [72% (95% CI 63-82) v 78% (95% CI 70-87), p=0.14] and 4-y OS was 95% (95% CI 91-99) with BR v 86% (95% CI 80-93) with Ibr (p=0.3). Premature discontinuation, during active treatment, due to adverse effects (AEs) or lack of response was noted in 13% and 33% of pts on BR and Ibr, respectively. A detailed assessment of the AEs will be presented at the meeting. Conclusions: Both BR and Ibr lead to comparable outcomes in pts with TN WM, although deeper responses are attained with BR. These findings require confirmation in prospective studies. For pts who harbor MYD 88L265P mutation, selection between the 2 approaches should be dictated by their potential toxicities, pt comorbidities, pt/clinician preference (parenteral fixed-duration v continuous oral) and access to therapies. [Table: see text]
A phase II, multicenter, single-arm study of parsaclisib, a PI3Kδ inhibitor, in relapsed or refractory follicular lymphoma in China: Updated data from the study.
Authors: Zheng Zhong , Zhang Huilai , Zhou Keshu , Zhou Hui , Zhang Li , Li Caixia , Zhou Min , Qian Wenbin , Li Zhiming , Zhang Qingyuan , Cheng Ying , Liu Peng , Li Zhenyu , Su Liping , Li Fei , Sun Xiuhua , Wang Jingwen , Gao Yuhuan , Zhao Xielan , Zhao Weili
Published: June 2022

7574

Background: For Follicular lymphoma (FL) patients (pts) of 3rd or higher line, treatment options are limited. Parsaclisib is a potent, highly-selective, next-generation PI3Kδ inhibitor. Initial safety and efficacy data were previously presented (Zhong Zheng et al. ASH 2021; NCT04298879). Here, we report safety, efficacy and survival data of the multicenter, open-label phase 2 study of parsaclisib in 3rd or higher line FL pts in China. Methods: Key eligibility included, age ≥ 18 years, histologically confirmed FL grade 1, 2, or 3a, ≥ 2 prior systemic therapies, ECOG PS ≤ 2, and ineligible for hematopoietic stem cell transplantation (HSCT). Pts received parsaclisib 20 mg once daily (QD) for 8 weeks followed by 2.5 mg QD, till disease progression (PD), unacceptable toxicity, death or withdrawn consent. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was required. Primary endpoint was objective response rate (ORR) evaluated by an Independent Review Committee (IRC) according to Lugano 2014 criteria, secondary endpoints included: duration of response (DOR), PFS, OS, and safety and tolerability. Results: As of the data cutoff date (Dec 12, 2021), 61 pts (median age: 50yr; male [n = 35, 57.4%]) were enrolled. Forty-eight pts remained on treatment and 13 pts had discontinued study treatment mainly due to PD (n = 11). With a median follow-up time 9.5 months (range 6.0-19.7months), the median duration of treatment was 251.0 days (range: 23.0-589.0 days). All 61 pts were evaluable for response, the ORR and complete response rate (CRR) were 86.9% (n = 53, 95% CI: 75.8-94.2%) and 31.1% (n = 19, 95% CI: 19.9-43.3%), respectively. The median time to response (TTR) was 8.0 weeks (95% CI: 7.9-8.0%), and the median DOR was not reached (95% CI: 9.2 months-NC), and 43 of 53 pts with CR or PR still retained CR or PR. As data cutoff, eleven (17.9%) pts had disease progression, the median PFS was not achieved. Three pts died data as data cutoff, the median OS was not achieved. Among the 61 treated pts, 48 (95.1%) pts experienced at least 1 treatment-emergent adverse events (TEAEs), with the most common TEAEs being neutrophil count decreased (49.2%), white blood cell count decreased (32.8%). Twenty-seven patients (44.3%) experienced grade ≥ 3 TEAEs, the most common grade ≥ 3 TEAEs was neutrophil count decreased (n = 10, 16.4%). Conclusions: Parsaclisib demonstrated promising efficacy, and acceptable safety profile. These results suggest that parsaclisib could benefit 3rd or higher line Follicular lymphoma patients. Clinical trial information: NCT04298879.
Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma.
Authors: Bansal Radhika , Baksh Mizba , Larsen Jeremy Todd , Hathcock Matthew , Dingli David , Stewart Keith , Kapoor Prashant , Kourelis Taxiarchis , Hayman Suzanne R. , Warsame Rahma M. , Fonseca Rafael , Bergsagel Peter Leif , Ailawadhi Sikander , Kumar Shaji , Lin Yi
Published: June 2022

8022

Background: Bone marrow (BM) assessment of minimal residual disease (MRD) is being considered as a surrogate endpoint in clinical trials and is prognostic for survival in multiple myeloma (MM). Timing of BM assessment is variable across Chimeric Antigen Receptor T cell (CART) therapy trials and differs from standard of care practice. BM myeloma cell clearance can be detected by month 1 post CART, even before serum immunofixation becomes negative. BM is still hypocellular at month 1, thus prognostic value of MRD negative (MRDneg) at this timepoint is unclear. We examined impact of Day 30 MRD status in patients (pts) who received CART at Mayo Clinic. Methods: Medical records were reviewed retrospectively for MM pts who received CART between 8/2016 and 6/2021. PFS and OS were plotted by Kaplan-Meier method. Results: Sixty MM pts received CART and had BM biopsy at month 1. Median age was 62 yrs, 53% were male, and 78% were BM MRDneg by flow cytometry. Baseline demographics were similar between MRDneg and MRD+ (Table). Overall, 85% (40/47) who were month 1 BM MRDneg had i/u FLC<normal. Patients who achieved CR/sCR had higher rates of BM MRDneg (100% vs 61%, p<0.001) and i/u FLC< normal (89% vs 58%, p<0.001). At month 1, 24/60 (40%) pts had hypocellular BM. Serial BM samples at month 3 (n=35), 6 (n=28) and 12 (n=23) showed MRDneg rate of 93% (25/27), 56% (9/16) 58% (7/12), respectively.. Rate of hypocellularity was 54% (19/35), 32% (9/28) and 30% (7/23), respectively. Among the MRDneg/hypocellular pts at month 1, hypocellular BM was seen in 8/11 (73%) pts at month 3 and 2/4 (50%) pts at month 6 and 12. Compared to MRD+, pts who had BM MRDneg at months1 had longer PFS (Table). PFS was not statistically significantly different between pts who had BM MRDneg and were either hypocellular or not. MRDneg pts with i/u FLCnormal: 4.9 months (2.3-NR). vs MRDneg/FLC<normal:17.9 months (11.8-NR), p<0.0001). Conclusions: Hypocellular BM is common in the 3 months post CART. Regardless of BM cellularity, BM MRDneg at month 1 correlates with deep response and prolonged PFS. Majority of BM MRDneg pts at month 1 also had FLC<normal. BM MRDneg status and FLC normalization were associated with longer survival. Our data support the continued evaluation of BM early post CART infusion as a prognostic tool. [Table: see text]
Determinants of overall survival (OS) of primary plasma cell leukemia (pPCL): A National Cancer Database (NCDB) analysis of years 2004 to 2009.
Authors: Landau Kevin Scott , Mowery Kelsey Lynn , Liang Hong , Fu Chieh Lin , Chaulagain Chakra Pani
Published: June 2022

8066

Background: Outcome data for pPCL is limited due to the rare & aggressive nature of the disease. In this retrospective analysis, we utilized NCDB to identify factors contributing to 1 & 5-year OS of pPCL patients treated at CoC-accredited facilities across USA. Methods: Using the NCDB, we identified N= 325 pPCL patients diagnosed between 2004-2009 after excluding entries missing relevant values. Univariate analysis was used to summarize & assess the potential survival factors individually & multivariate Cox regression analysis with backward elimination (using significance level of p<0.05) was utilized to identify the independent survival factors. Kaplan-Meier (KM) survival curves of patient cohort were also produced. SAS version 9.4 was used to analyze the data. Results: Multivariate Cox regression analysis with backward elimination method revealed that there were 4 significant independent survival factors including sex, Charlson-Deyo Comorbidity Index (CCI), facility type, and insurance, while age & year-of-diagnosis were not independent survival factors (Table). Male patients were more likely to die compared to female patients (HR=1.40, p=0.005); patients with CCI ≥1 had higher chance to suffer death compared to patients with CCI= 0 (HR=1.52, p=0.002); patients not treated at an academic center (AC) had lower survival compared to those treated at ACs (HR=1.35, p=0.001); and patients without private insurance (PI) were more likely to suffer death compared to those with PI (HR=1.54, p=0.001). The 1 & 5-year survival rates for whole cohort were 51.3% (95%CI: 45.8%-56.8%), and 18.9% (95%CI: 14.6%-23.2%) using KM estimate, respectively. Only 6/325 =1.8% patients underwent autologous hematopoietic stem cell transplant (HSCT). Detailed analysis will be presented. Conclusions: In this large analysis of pPCL patients, we identified that being female, having less comorbidities, getting treatment at ACs, and having PI had significantly greater OS. Overall, pPCL is associated with low survival rates both at 1 & 5-years and HSCT may be enormously under-utilized for pPCL patients in the real world setting. [Table: see text]