bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovarian function suppression in premenopausal patients with concurrent endocrine therapy use.
Authors: Grogan Nicole Margo , Li Yajing , Kidwell Kelley M. , Henry Norah Lynn 
Published: June 2021

6574 Background: The addition of ovarian function suppression (OFS) to endocrine therapy (ET) for premenopausal women with high risk, hormone receptor-positive breast cancer improves disease outcomes. However, in the SOFT-EST study, up to 17% of patients receiving gonadotropin-releasing hormone agonists (GnRHa) did not have appropriate ovarian suppression within the first year of treatment. Few studies have explored the long-term effectiveness of OFS to maintain estrogen suppression. Guidelines for estradiol monitoring during OFS therapy are not clearly defined. Methods: We performed a retrospective, single institution review of all patients who received concurrent GnRHa injections and ET since 2010. Only estradiol concentrations that were assessed during OFS treatment were abstracted from the medical record and included in the analysis. The primary endpoint was the percentage of patients with a non-suppressed estradiol concentration (defined as standard estradiol or high-sensitivity estradiol ≥ 10 pg/ml) identified during OFS cycle 2 ( > 35 days after OFS initiation) and/or later cycles. The secondary endpoint, which included only those patients with estradiol assessment within 35 days of OFS initiation, was the percentage of patients with a non-suppressed estradiol level when measured within the first 35 days after OFS initiation. For both cohorts, differences in age, body mass index (BMI), and previous chemotherapy use were summarized via multivariable logistic regression. Results: 148 patients received concurrent OFS and ET. Patients were excluded because of lack of estradiol assessment during OFS therapy (n = 13) and non-compliance with GnRHa injections (n = 4). The average age and BMI were 43.1 years and 29.1 kg/m2, respectively. 35 of 131 patients (26.7%) had at least one non-suppressed estradiol level during OFS cycle 2 and/or later cycles. The median time to detection of non-suppression was 250 days (range: 53 – 2573 days). Patients whose estradiol concentration remained suppressed throughout treatment with OFS and ET were more likely to be older (OR 1.12 [95% CI 1.05-1.22], p =.02), have a lower BMI (OR 0.88 [95% CI 0.82-0.94], p <.001), and have received chemotherapy (OR 6.30 [95% CI 2.06-20.8], p =.002). For the secondary endpoint, 20 of 83 patients (24.1%) had a non-suppressed estradiol level within 35 days of OFS initiation. Lower BMI was associated with achieving ovarian suppression by 35 days (OR 0.85 [95% CI 0.77-0.93], p <.001); no association was noted for age or chemotherapy. Conclusions: More than one-fourth of patients in this “real world” population had at least one non-suppressed estradiol level during treatment, both the month after the initial OFS dose and at later time points. Patients on OFS, especially those on aromatase inhibitor therapy and those at increased risk of non-suppression, may require frequent and long-term estradiol monitoring during treatment.
Identifying gaps in the coverage of survivorship care services.
Authors: Blaes Anne Hudson , Abu-Khalaf Maysa M. , Bender Catherine M. , Dent Susan Faye , Fung Chunkit , Smith Sophia Kustas , Watson Samantha , Katta Sweatha , Merrill Janette K. , Hudson Shawna V. 
Published: June 2021

6583 Background: Despite advancements in reimbursement, anecdotal evidence suggests patients are not able to access guideline concordant survivorship care services due to a lack of coverage by payers. We present the results of a mixed methods study aimed to determine the practice-reported rates and sources of delay/denial on evidence-based, guideline concordant survivorship care services. Methods: A quantitative survey was developed by ASCO’s Cancer Survivorship Committee (CSC) to assess which services are being denied by payers for coverage/reimbursement. Questions were limited to disease sites for which practice guidelines exist. 533 ASCO members who provide survivorship care were surveyed, with a focus on obtaining representation from rural/urban, academic/private practice, pediatric/adult, and geographic location across the U.S. Semi-structured telephone interviews were conducted in October and November 2020 with geographic sub sample representation to further explore the nature of and extent to which coverage barriers are experienced for guideline-concordant care, specific to the provider or clinic’s primary disease site or specialty. Results: 120 responses from 50 states were included. Respondents were primarily clinicians (88%) with the majority treating patients with Medicare/Medicaid/CHIP (60%), followed by private/employer insurance (38%). There was little issue with coverage of hormone therapies. One-third reported issues some of the time with maintenance chemotherapy (38%) and immunotherapy (35%). Coverage denials for screening for recurrence for breast cancer (MRI, 63.5%), Hodgkin Lymphoma (PET/CT 47%; Breast MRI, 44.4%), and lung cancer (Low-dose CT 37.4%) were common. Half of the survey respondents reported denials for supportive care/symptom management services (Table). Private or employer-based insurance denials were most often the source of barriers (57.7%). Through interviews, denials were found to be the same across sites and not unique to a single payer or region. Most had a process to appeal denials for evidence-based services. Conclusions: Denial for survivorship care, particularly supportive care services, is common. There is a need for better advocacy with payers, improved policy, and support for providers/practices to implement protocols to obtain coverage for services, particularly in the face of burnout.[Table: see text]
Timing of steroid use and outcomes of immune checkpoint inhibitor: A population based study.
Authors: Nikita Nikita , Johnson Jennifer Maria , Wilson Melissa , Banks Joshua , Keith Scott W. , Sharma Swapnil , Lu-Yao Grace L. 
Published: June 2021

6590 Background: Immune checkpoint inhibitors (ICIs) have rapidly become the treatment of choice for multiple cancer types. However, the relationship between the timing of immunosuppressive agents, such as steroids use, preceding ICI initiation and subsequent treatment outcomes remains unknown due to lack of data. This study was undertaken to address this knowledge gap. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data to identify patients with melanoma receiving Ipilimumab, Nivolumab, Pembrolizumab, or Ipilimumab/Nivolumab combination in 2010-2015. Last steroid exposure within 12 months prior to ICI use was categorized (none, 0-1, 1-3, and 3-12 months prior). Cox models were used to generate covariate-adjusted hazard ratios of overall mortality following ICI initiation. Because the hazards were not proportional over time, we allowed the hazard ratios to differ in three periods (<3, 3-6, and more than 6 months post ICIs). Results: We identified 3,149 melanoma patients (median age 68 years) using ICIs; among these 1,352 received steroid within 12 months prior. Steroid use within 1 month prior to using ICIs was associated with a 93% and 102% increased risk in overall mortality within 3 months and 3-6 months post ICI initiation. The risk diminished over time (Table). A similar pattern was observed for steroid use 1-3 months prior. Steroid use beyond 4 months prior to ICI was not associated with increased mortality. Conclusions: This was the first major study to document that timing of steroid use prior to ICI is associated with the risk of mortality and how the increased risk diminishes over time. Further studies are warranted to confirm the findings and understand potential mechanisms.[Table: see text]
Fixed-duration (FD) first-line treatment (tx) with ibrutinib (I) plus venetoclax (V) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of the FD cohort of the phase 2 captivate study.
Authors: Ghia Paolo , Allan John N. , Siddiqi Tanya , Kipps Thomas J. , Jacobs Ryan , Opat Stephen , Barr Paul M. , Tedeschi Alessandra , Trentin Livio , Bannerji Rajat , Jackson Sharon , Kuss Byrone , Moreno Carol , Szafer-Glusman Edith , Russell Kristin , Zhou Cathy , Ninomoto Joi Suzuki , Dean James P. , Wierda William G. , Tam Constantine Si Lun 
Published: June 2021

7501 Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of first-line I+V in CLL. We previously reported results from the Minimal Residual Disease (MRD) cohort wherein undetectable MRD (uMRD) was achieved in over two-thirds of patients (pts) with 12 cycles of I+V, and 30-mo PFS rates were ≥95% irrespective of subsequent randomized treatment (Wierda, ASH 2020). We now present results from the FD cohort, evaluating fixed-duration tx with I+V. Methods: Pts aged ≤70 y with previously untreated CLL/SLL received 3 cycles of I then 12 cycles of I+V (I 420 mg/d orally; V ramp-up to 400 mg/d orally). Primary endpoint was CR rate, including CR with incomplete recovery (CRi); secondary endpoints were ORR, duration of response, uMRD rate (<10-4 by 8-color flow cytometry), PFS, OS, tumor lysis syndrome (TLS) risk reduction, and adverse events (AEs). Results: 159 pts were enrolled (median age 60 y). High-risk features included del(17p)/ TP53 mutation, 17%; del(11q), 18%; complex karyotype, 19%; and unmutated IGHV, 56%. 147 (92%) and 149 (94%) pts completed planned tx with I and V, respectively. Median time on study was 27.9 mo (range, 0.8–33.2). With fixed-duration I+V, CR rate was 55% (95% CI 48–63) in the overall population and was consistent across high-risk subgroups. Of the 88 pts who achieved CR, 78 (89%) had durable CR (duration ≥1 y); 1 died 7 mo after CR, and 9 with <1 y follow-up were not evaluable. ORR was 96%. Best uMRD response was achieved in 77% of pts in peripheral blood (PB) and 60% of pts in bone marrow (BM). 24-mo PFS was 95%; 24-mo OS was 98%. Results were similar in pts without del(17p) (n=136) (Table). In pts with del(17p)/ TP53 mutation (n=27), CR rate was 56%, uMRD rate was 81% (PB) and 41% (BM), and 24-mo PFS was 84% (95% CI 63–94). Of 34 pts with high baseline TLS risk based on tumor burden, 32 (94%) shifted to medium or low risk after I lead-in; no TLS occurred. AEs were primarily grade 1/2. Most common grade 3/4 AEs were neutropenia (33%), hypertension (6%), and neutrophil count decreased (5%). AEs led to discontinuation of I in 4% and V in 2%. Conclusions: First-line I+V is an all-oral, once-daily, chemotherapy-free, fixed-duration regimen that provides deep, durable responses in pts with CLL/SLL, including those with genomic high-risk features. CR, uMRD rates, PFS, and OS appear favorable. The safety profile of I+V was consistent with known AEs for each agent; no new safety signals were identified. Clinical trial information: NCT02910583. [Table: see text]
Obinutuzumab (G)-atezolizumab (atezo)-lenalidomide (len) for the treatment of relapsed/refractory (R/R) follicular lymphoma (FL): Final analysis of a phase Ib/II trial.
Authors: Ghosh Nilanjan , Salles Gilles A. , Lossos Izidore S. , Palomba Maria Lia , Mehta Amitkumar , Casasnovas Olivier , Stevens Don A. , Katakam Sudhakar , Knapp Andrea , Nielsen Tina , Morschhauser Franck 
Published: June 2021

7511 Background: G-len has promising activity and manageable toxicity in R/R FL (Morschhauser et al. 2019). We report the final analysis of an open-label, multicenter, Phase Ib/II trial (NCT02631577) that evaluated the immunomodulatory triplet G-atezo-len in pts with R/R FL. Methods: An initial 3+3 dose‐escalation to identify the Phase II len dose was followed by an expansion phase with G-atezo-len. Enrolled pts (aged ≥18 years) received induction with 6, 28-day cycles of G 1000 mg IV on Day [D] 1, 8, and 15 of Cycle [C] 1 and D1 of C2–6, atezo 840 mg IV on D1 and 15 of C2–6, and len 15/20 mg (dose escalation) or 20 mg (expansion) orally on D1–21 of C1–6. Responders received 24 months (mos) of maintenance with G 1000 mg D1 every 2 mos, atezo 840 mg D1–2 every mo, and len 10 mg D1–21 mos 1–12. The primary endpoint was complete response at end of induction by PET-CT assessed by Independent Review Committee (modified Lugano 2014 criteria; Morschhauser et al. ICML 2019). Exploratory endpoints described herein included progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Adverse events (AEs) were also assessed. Results: At the final analysis (October 7, 2020), 38 pts had completed the trial. Median age was 62 years, 26% had a high-risk FLIPI score, 45% were refractory to their last line of therapy, and 37% had progression of disease within 24 mos of their first-line of therapy (POD24). Median treatment duration was 26 mos (range: 0.4‒30). The 36-mo PFS rate for the overall population (median observation time, 35.9 mos; range: 3‒47) was 64% (95% CI, 45‒79), OS was 85% (95% CI, 70‒93), and median DOR was 38 mos (95% CI, 35‒NE). 36-mo PFS rates for the following subgroups are provided in the table: double refractory (rituximab and an alkylator); with/without POD24; minimal residual disease (MRD) +/-. In total, 32 pts (84%) had a Grade 3/4 AE (majority hematologic), and 18 (47%) had a serious AE. Five pts (13%) during induction and six pts (16%) during maintenance had an AE that led to discontinuation of any drug. Two fatal AEs were reported (1 merkel carcinoma, 1 sarcomatoid carcinoma; both unrelated to any study drug). The most common atezo AEs of special interest were hyperthyroidism (13%), hypothyroidism (11%), increased ALT and AST (both 8%), increased lipase (8%), and hepatocellular injury (5%). Conclusions: G-atezo-len is efficacious in pts with R/R FL, with data from the final analysis suggesting a potential for improved outcomes versus the G-len doublet. AEs were consistent with the safety profile of the individual drugs. Clinical trial information: NCT02631577. [Table: see text]
Effect of time to relapse on overall survival (OS) in mantle cell lymphoma (MCL) patients (pts) following frontline high-dose therapy and autologous hematopoietic cell transplantation (autoHCT).
Authors: Riedell Peter A. , Hamadani Mehdi , Ahn Kwang Woo , Litovich Carlos , Kharfan-Dabaja Mohamed , Herrera Alex Francisco , Sauter Craig Steven , Smith Sonali M. 
Published: June 2021

7521 Background: In MCL, outcomes are heterogeneous and the clinical significance of the timing of relapse following autoHCT and its impact on OS is not well defined. Using the CIBMTR database, we evaluate the effect of post-autoHCT time to relapse on OS over time. Methods: Adult MCL pts treated with up to two lines of rituximab-based induction therapy followed by first autoHCT within 1-year of diagnosis were identified between 2000-2018. Primary outcomes included OS and post-relapse OS. A dynamic landmark analysis was performed at 6-month intervals following autoHCT to evaluate the impact of relapse on OS while adjusting for significant patient- and disease-related variables. Post-relapse OS was evaluated in pts who experienced relapse. Results: Of the 461 pts included in the analysis, the median age was 60 years (range 29-78), 57% had a KPS of ≥ 90, 83% had stage III-IV disease at diagnosis, and 76% had extranodal involvement. BEAM was the most common conditioning regimen (58%) and 23% of pts received post-autoHCT maintenance rituximab. With a median follow-up of 67 months, the 5-year progression-free survival was 45.8% with a 5-year OS of 69.6%. On multivariate analysis, age ≥60 years was associated with worse OS (HR= 1.55, 95% CI 1.08-2.24, p=0.0191) at all landmark timepoints. Additionally, the impact of relapse on OS varied with time (p=0.006) and was greatest at the 6-month (HR=7.68), 12-month (HR=6.68), and 18-month (HR=5.81) landmark timepoints. The risk of death for relapsing pts decreased with time and was mirrored by an improvement in adjusted OS for both relapsing and non-relapsing pts. In total, 9.3% of patients relapsed prior to the 18-month landmark timepoint. Relapse at the 6-month, 12-month, and 18-month landmark timepoints correlated with a poor median post-relapse OS of 9 months, 24 months, and 34 months, respectively (Table). Conversely, patients relapsing after the 18-month landmark timepoint experienced a median post-relapse OS ranging from 44-67 months. Conclusions: In MCL, early relapse (< 18-months) following autoHCT defines a high-risk group with inferior post-relapse OS. This population should be considered for clinical trials or novel therapeutic approaches including early utilization of chimeric antigen receptor T-cell therapy.[Table: see text]
Combination of sintilimab, anlotinib and pegaspargase "sandwich" with radiotherapy in localized natural killer/T cell lymphoma: A multicenter, phase 2 study.
Authors: Li Zhiming , Sun Peng , Wang Yu , Yang Hang , Li Yajun , Zhou Hui , Yang Haiyan , Zou Liqun 
Published: June 2021

7537 Background: NK/T-cell lymphoma (NKTL) is a rare and distinct subtype NHL. Most newly diagnosed NKTL cases were localized-stage. For localized NKTL, RT alone is inadequate due to high systemic failure rate. Chemoradiation has been increasingly applied. However, current chemotherapy (CT) regimens have severe toxicity and infection, which reduce the completion of RT and patients’ medical compliance. Therefore, novel regimens with mild toxicity are needed. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has showed encouraging antitumor efficacy in pts with r/r NKTL. Anlotinib, a multiple-targeted TKI that mainly blocks VEGF/VEGFR pathway, has been approved for several solid tumor types in china. Anti-angiogenesis therapy could improve efficacy of ICI in multiple tumor types. This multicenter, single-arm, phase 2 study aims to evaluate the efficacy and safety of sandwich chemoradiotion of sintilimab combined with anlotinib and pegaspargase (PEG-ASP) in newly diagnosed localized NKTL pts. Methods: Patients with pathologically confirmed previously untreated stage NKTL were enrolled. All enrolled patients received 3 cycles of sintilimab (200mg D1 ivdrip) combined with anlotinib (12mg po D1-14) and PEG-ASP (2500U/m2 D1) every 3 weeks followed by RT, then received additional 3 cycles of combination therapy as described above. The primary endpoint was overall response rate (ORR) by LUGANO 2014 criteria. Results: A total of 39 pts were enrolled, and 24 pts eligible for response evaluation (70.8% men; median age, 46 y [range 20-64]; 58.3% stage). According to PINK-E system, 8 pts (33.3%) were identified as intermediate risk group and 16 patients were low risk group. 23 of 24 patients completed protocol-specified therapeutic schemes, one patient discontinued the study after the second cycle due to disease progression. ORR was 95.8% (23/24, 95%CI: 76.9%-84.1%). Surprisingly, all the responded patients achieved CR, while 66.7% (16/24, 95%CI: 44.7%-83.6%) patients achieved CR after the second cycle. Median PFS and OS have not been reached. 1-year OS and PFS was 100% and 95.8%, respectively. All grade TRAEs occurred in 84.6% of all enrolled patients and 92.1% were grade 1-2. The most common TRAE was lymphocytopenia (9.9%). Of note, grade 3-4 hematological toxicity was reported in only one patient (4.2%). All AEs were resolved after symptomatic treatment, without systematic corticosteroid intervention. Conclusions: Sintilimab combined with anlotinib and PEG-ASP upfront and after radiotherapy was effective and could be well tolerated in localized NKTL, achieving promising CRR and rapid and long-term remission with mild toxicity. Further investigation of survival outcome is warranted. Clinical trial information: NCT03936452.
Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.
Authors: Canales Albendea Miguel Angel A. , Buchholz Thomas A. , Izutsu Koji , Ishikawa Takayuki , Fogliatto Laura Maria , Vorozheikina Ekaterina , Klingbiel Dirk , Pokala Sunny , Tomiczek Monique , Parreira Joana , Hübel Kai 
Published: June 2021

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]