bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of patient-reported impact of COVID19 on cancer care delivery: A prospective, cross-sectional study.
Authors: Hsu Emily , Chhabra Jyoti , Serrano Oscar , Menendez Alvaro G.
Published: June 2021

6551

Background: Impact of COVID19 on cancer care delivery and outcomes remains unknown. Few trials have investigated patients’ perceived risks and benefits, and cancer care delivery (CCD) alterations related to COVID19. We sought to identify differences on behaviors and social determinants of health in Hispanics and other underrepresented populations (H/UP) compared to the general population (GP). Methods: An IRB-approved validated 27-item questionnaire was offered in English and Spanish to all pts. receiving cancer care at participating cancer centers over a 4 month period. Examined variables included demographic information, social risk and behavioral factors, preferred sources of health information, and overall satisfaction with CCD during the pandemic. Results: A total of 180 pts were enrolled in the study. Compared to GP, H/UP’s perceived risk of COVID19 was higher with 93% vs 87% more likely to cancel or avoid social gatherings and 54% vs 46% more likely to change daily routine. H/UP appeared more concerned with personal and financial safety; if unable to find work/get paid for 2 weeks, 26% H/UP vs 10% GP would struggle to keep up with expenses. 40% H/UP vs 10% GP have concerns on perceived ability to secure food on short term and consider COVID19 a major threat to their health (70% vs 46%) and financial situation (63% vs 35%). H/UP’s perceived benefits of protective measures is higher with 81% vs 60% routinely practicing social distancing (SD) and 79% vs 66% in agreement with punitive actions for not following SD. Analysis demonstrated no significant difference by age, gender, level of education, marital status, however Hispanic ethnicity and Spanish as primary language was a statistically significant variable (p = 0.025) in perceived risks and satisfaction with CCD. No major differences were noted on sources of health information although more H/UP relied on social media (33% vs 24%). H/UP appeared to be more skeptical about availability and safety of targeted vaccines (40% vs 15%). Satisfaction regarding CCD was comparable (84% vs 86%), although more H/UP perceived CCD alterations (15% vs 10%). Going forward, H/UP would prefer to incorporate virtual visits (VV) when possible (36% vs 25%). Conclusions: COVID19-related societal, financial, health and personal fears are increased in H/UP which likely negatively affects quality of life of these at-risk populations. H/UP’s trust in SD recommendations is heightened although linguistically and culturally appropriate information may be deficient. H/UP’s belief in vaccine availability and safety is comparable to GP, although recent reports suggest deeper fear and emphasize their fear of experimentation. Interventions aimed to decrease these differences could incorporate standard communications with special attention to social media. H/UP would prefer to incorporate VV into their care, although most do not possess appropriate technology to do so.
Examining racial disparities in male breast cancer.
Authors: Linehan Elizabeth Shurell , Samant Navendu D. , Rabbani Juleon W
Published: June 2021

6555

Background: Male breast cancer (MBC) accounts for approximately 1% of all breast cancers. Racial disparities have not been examined in MBC. Methods: Within a large, integrated health delivery system, all adult female and male patients who were diagnosed with breast cancer from 01-01-2010 to 12-31-2018 were examined. Bivariate analysis was performed to examine clinical and demographic factors associated with breast cancer-related mortality. We conducted more detailed chart review in the MBC-only group (data period 01-01-2010 to 12-31-2019) to assess the mean time to treatment (from diagnosis to surgery, surgery to chemotherapy, and surgery to radiation) stratified by race using bivariate (t-test, one way ANOVA) analyses. Results: 32,848 female breast cancer and 226 MBC patients were evaluated; MBC patients represented 0.63% of all breast cancer patients. Between males and females, there was no statistically significant difference in race, with an overall distribution of 62% White, 19% Asian, 8% Black, and 11% Hispanic. To our knowledge, this is the largest and most racially diverse sample of MBC patients to date. MBC patients at diagnosis were significantly older (p <.0001), more obese (p < 0.0018), and sicker according to the Charlson Comorbidity Index (CCI) (p < 0.0001) compared to female breast cancer patients. Males were more likely to be diagnosed at an advanced stage (19.2%) compared to females (12.5%) (p = 0.0037). With a mean follow up of 5 years, overall mortality was statistically significantly worse in MBC (23.0%) compared to female breast cancer patients (12.0%) (p < 0.0001). Furthermore, breast cancer-related mortality was significantly higher in males (8.1%) than in females (4.5%) (p = 0.0124). In the MBC-only analysis, stage at diagnosis was not influenced by patient race. Asian and White MBC patients had the shortest mean time from diagnosis to surgery (27 and 29 days, respectively), with Hispanic MBC patients experiencing the longest time to surgery (46 days). Black MBC patients experienced the shortest mean time to chemotherapy after surgery (39 days), whereas Asian MBC patients experienced the longest time to chemotherapy (50 days). In survivorship, Black and Asian patients were least likely to undergo screening mammography (33.3%, and 43.3%, respectively), compared to 52% of White and 50% of Hispanic MBC patients. Ultimately, 13% of Asian and 11% of Hispanic MBC patients died of breast cancer, compared to 6.7% of Black and 6.2% of White MBC patients. Conclusions: While we found no statistically significant differences in mortality by race among MBC patients, our findings indicate that non-white patients had longer time to treatments, less survivorship screening, and worse disease related mortality than their white counterparts. Future study can elucidate these racial inequalities, enabling more equitable breast cancer treatment among patient subgroups.
In-hospital outcomes of CAR T-cell therapy in United States in 2018: A nationwide analysis.
Authors: Rai Manoj P. , Bedi Prabhjot Singh , Kasi Anup , Mehta Kathan
Published: June 2021

6556

Background: CAR T-cell therapy is a type of adoptive cell transfer (ACT). In 2017 CAR T-cell therapy was approved by the Food and Drug Administration (FDA) for management of diffuse large B-cell lymphoma refractory to at least two prior lines of therapy (DLBCL) including primary mediastinal large B-cell lymphoma (PMBCL), and B cell precursor acute lymphoblastic leukemia (ALL) up to 25 years of age that is refractory or in second or later relapse. Since its inception, several patients underwent CAR T-cell therapy but data on real world outcome is limited. In this study we aim to evaluate the in-hospital outcomes of CAR T-cell therapy in the United States in 2018. Methods: This is a cross-sectional study using National Inpatient Sample 2018 database. Discharges with the ICD-10-PCS code for CAR T-cell therapy and ICD-10-CM code of ALL, DLBCL or PMBCL were included in the study. We analyzed their in-hospital outcomes (Total discharges, length of stay in days, hospitalization cost, and mortality - number of deaths). We applied the cost to charge ratio to hospitalization charges to estimate the mean hospitalization cost. The weighted sample represents national estimates. Results: We identified 785 discharges with CAR T cell therapy and diagnosis of ALL, DLBCL or PMBCL. 155 (19.75 %) were ALL, 620 (78.98%) DLBCL, and 10 (1.27%) PMBCL. Mean length of stay for the study cohort was 23.26 days. Specifically, for ALL mean LOS was 33.67 days, DLBCL 20.76 days, and PMBCL 17 days. Mean hospitalization cost for the study cohort was $285,989, specifically for ALL it was $342,228, DLBCL $274,102, PMBCL $179,431. There were a total of 60 (7.6%) deaths in the study cohort. Diagnosis specific mortality was 20 (12.9%) in ALL, 40 (6.4%) in DLBCL and none in PMBCL. Conclusions: Majority of discharges who underwent CAR T-cell therapy were DLBCL followed by ALL and PMBCL. CAR-T Cell hospitalizations have high costs and long length of stays. Mean length of stay was highest in ALL discharges, least in PMBCL. Mean hospitalization cost was higher in DLBCL discharges compared to ALL and was least in PMBCL discharges. The in-hospital mortality with the CAR-T cell therapy appears to be higher than reported in clinical trials, especially for ALL. [Table: see text]
Lower respiratory tract disease (LRTD) in patients with cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) study.
Authors: Shah Dimpy P , Shah Pankil , Schmidt Andrew Lachlan , Bakouny Ziad , Farmakiotis Dimitrios , Abidi Maheen , Rubinstein Samuel M. , Figueroa Cesar J. , Labaki Chris , Friese Christopher Ryan , Rathmann Joerg , Hwang Clara , McKay Rana R. , Park Cathleen , Puc Matthew , Nagaraj Gayathri , French Benjamin , Warner Jeremy Lyle , Shete Sanjay
Published: June 2021

6563

Background: Immunodeficiency in patients (pts) with cancer can lead to the progression of common respiratory viral infections to lower respiratory tract disease (LRTD) with potentially high mortality. Understanding risk factors of SARS-CoV-2 related LRTD in pts with cancer is imperative for the development of preventive measures. Methods: We examined all patients aged 18 years or older with cancer and laboratory-confirmed SARS-CoV-2 infection reported between March 16, 2020 and February 6, 2021 in the international CCC19 registry. We examined frequency of LRTD (pneumonia, pneumonitis, acute respiratory distress syndrome, or respiratory failure), demographic and clinicopathologic factors associated with LRTD, and 30-day and overall mortality in pts with and without LRTD. Results: Of 7,289 pts with a median follow-up time of 42 (21-90) days, 2187 (30%) developed LRTD. Pts of older age (65 yrs or older), male sex, pre-existing comorbidities, baseline immunosuppressants, baseline corticosteroids, and ECOG performance status of 2 or more had substantially higher rates of LRTD compared to those without these risk factors (Table). We did not observe differences in LRTD rates between pts of different racial/ethnic groups, smoking history, hypertension, obesity, cancer status, timing or type of anti-cancer therapy. LRTD was more likely in pts with thoracic malignancy (39%), hematological malignancy (39%) compared to those with other solid tumors (27%). The majority of pts (86%) had symptomatic presentation; however, 8% of pts with asymptomatic presentation developed LRTD. 30-day and overall mortality rates were significantly higher in pts with LRTD than those without LRTD (31% vs. 4% and 38% vs. 6%, P < 0.05). Conclusions: COVID-19 related LRTD rate is high and associated with worse mortality rates in pts with cancer. The majority of risk factors associated with LRTD demonstrate underlying immunodeficiency or lung structural damage as a driving force in this population. Identifying pts at high-risk for developing LRTD can help guide clinical management, improve pt outcomes, increase the cost-effectiveness of antiviral therapy, and direct future clinical trial designs for vaccine or antiviral agents.[Table: see text]
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]
Efficacy and safety of the PI3Kδ inhibitor zandelisib (ME-401) on an intermittent schedule (IS) in patients with relapsed/refractory follicular lymphoma (FL) with progression of disease within 24 months of first-line chemoimmunotherapy (POD24).
Authors: Pagel John M. , Reddy Nishitha , Jagadeesh Deepa , Stathis Anastasios , Asch Adam Steven , Salman Huda S. , Kenkre Vaishalee Padgaonkar , Soumerai Jacob Drobnyk , Llorin-Sangalang Judith , Gorbatchevsky Igor , Li Joanne , Zelenetz Andrew David
Published: June 2021

7550

Background: FL patients (pts) with POD24 have poorer survival and may benefit from novel therapies at relapse. Zandelisib, a potent, selective, and structurally differentiated oral PI3kδ inhibitor was evaluated in a dose escalation/expansion Phase 1b study for FL demonstrating a high objective response rate (ORR) and well tolerated when given on IS (J Clin Oncol 2020;38:#8016). We report here results based on POD24 status (NCT02914938). Methods: Eligible pts had ≥1 prior therapy, adequate bone marrow and organ function, ECOG performance status ≤2, and no prior PI3K therapy. Zandelisib was administered at 60 mg once daily for 8 weeks followed by IS on days 1-7 of each subsequent 28-day cycle, either as monotherapy or with rituximab at 375 mg/m2 for 8 doses in Cycles 1-6. Treatment was continued until disease progression, intolerance, or withdrawal of consent. Imaging scans were obtained after 2 and 6 cycles, and then every 6 cycles. Response was reported based on Lugano criteria. Results: 37 FL pts were enrolled and received zandelisib on IS as monotherapy (N = 18) or in combination with rituximab (N = 19). Median number of prior therapies = 2 (range, 1-5). The ORR was 86.5% (32/37) with 27% CR (complete response). In the monotherapy group the ORR and CR were 77.8 % (14/18) and 27.8% and with rituximab 94.7% (18/19) and 26.3% respectively. Median duration of response (DOR) among all pts was not reached with a median follow-up of 16.9 months (mos) (1.2-33.1+). 22 pts (59%) were POD24, of which 15 (68%) had ≥2 prior lines of therapy. Despite more refractory disease, ORR among the POD24 pts was 81.8% (Table). Zandelisib on IS was well tolerated. 3 pts (8%) discontinued therapy due to an adverse event (AE) for any cause. Grade (Gr) 3 AE of special interest (AESI) were 2 (5.4%) diarrhea, 2 (5.4%) colitis, 3 (8.1%) rash, 3 (8.1%) ALT elevation, 1 (2.7%) AST elevation and no pulmonary infection. Conclusions: Zandelisib administered on IS as monotherapy or with rituximab resulted in a high-rate of durable responses in FL, both in POD24 and non-POD24 groups and therapy was well-tolerated with low rate of Gr 3 class-related AESI and discontinuation rate due to AE’s. Zandelisib as monotherapy is being evaluated in a global Phase 2 study in FL and MZL after failure of 2 prior therapies (NCT03768505). A Phase 3 study of zandelisib plus rituximab in FL and MZL after failure of prior immunochemotherapy will begin enrollment in 2021. Clinical trial information: NCT02914938. [Table: see text]
Long-term follow-up results of a phase II study of dose-adjusted (DA)-EPOCH-R with high-dose methotrexate (HD-MTX) for newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL).
Authors: Miyazaki Kana , Sakai Rika , Iwaki Noriko , Yamamoto Go , Yamada Tomomi , Nishimura Yuki , Tamaru Satoshi , Asano Naoko , Miyawaki Kohta , Izutsu Koji , Kinoshita Tomohiro , Suzuki Ritsuro , Ohshima Koichi , Kato Koji , Katayama Naoyuki , Yamaguchi Motoko
Published: June 2021

7551

Background: CD5+ DLBCL is characterized by a poor prognosis and frequent central nervous system (CNS) relapse after standard immunochemotherapy. In the primary analysis of our multicenter phase II study of DA-EPOCH-R/HD-MTX for newly diagnosed stage II-IV CD5+ DLBCL, the 2-year (yr) progression-free survival (PFS) was 79% and the 2-yr CNS relapse rate was 9% at a median follow-up of 3.1 yrs (Miyazaki, et al. 2020). The aim of this preplanned 5-yr follow-up was to assess PFS, overall survival (OS), the CNS relapse rate, and late toxicity. Methods: A total of 47 patients (pts) with newly diagnosed stage II-IV CD5+ DLBCL between 20-75 yrs old and ECOG PS of 0-3 were enrolled. The treatment included 4 cycles of DA-EPOCH-R followed by 2 cycles of HD-MTX (3.5 g/m2) and 4 additional cycles of DA-EPOCH-R. Intrathecal administration of MTX and/or cytarabine was not allowed. 45 (96%) pts completed the protocol treatment. The data were updated as of December 1, 2020. Results: The median follow-up of alive pts was 6.0 yrs (range, 5.0-7.7). The pts’ characteristics were as follows: age, 37-74 yrs (median, 62); male, 38%; ECOG PS > 1, 4%; stage III/IV, 57%; IPI HI/H, 47%; CNS-IPI high, 21%; and ABC/GCB/unclassified (n = 46), 85%/9%/7%. The 5-yr PFS and OS were 72% (95% CI, 57-83%) and 79% (95% CI, 64-88%), respectively. The 5-yr PFS and OS of pts with CD5+ ABC DLBCL (n = 39) were 72% and 74%, respectively. The 5-yr CNS relapse rate in all 47 pts was 9% (95% CI, 3-22%). There were no CNS relapse events after the primary analysis. Neither grade 3/4 late adverse events nor cardiac events of any grade were observed. Possible second malignancies were recorded in 6 (13%) pts. Among them, one pt who received R-ICE as salvage therapy experienced acute myeloid leukemia. The other 2 pts had colon cancers treated with endoscopic polypectomy/mucosal resection. Conclusions: Both the survival benefit and safety of DA-EPOCH-R/HD-MTX were maintained during a 5-yr follow-up, indicating the excellent efficacy, and safety of this approach as a first-line therapy for CD5+ DLBCL. Clinical trial information: UMIN000008507.
Surgical outcomes for early-stage non-small cell lung cancer at facilities with stereotactic body radiation therapy programs.
Authors: Syed Yusef , Stokes William A. , Khullar Onkar , Sebastian Nikhil , Rupji Manali , Yuan Liu , Bradley Jeffrey D. , Higgins Kristin Ann , Curran Walter J , Ramalingam Suresh S. , Sancheti Manu , Fernandez Felix , Moghanaki Drew
Published: June 2021

8538

Background: Patients undergoing surgery for early-stage non-small cell lung cancer (NSCLC) may be at high-risk for post-operative mortality. Access to stereotactic body radiation therapy (SBRT) offers a less invasive alternative for this population that may facilitate more appropriate patient selection for surgery. Methods: An analysis of all patients with early-stage NSCLC reported to the National Cancer Database between 2004-2015 was performed. Post-operative mortality rates were derived using vital status data. Utilization of SBRT was defined by each facility’s SBRT Experience in years and SBRT-to-Surgery volume ratios, defined by quartiles. Multivariable logistic regression with backward elimination was used to test for independence of associations between exposures of interest and post-operative mortality. Interaction testing was performed to assess the statistical relationship of covariates found to have independent associations. Results: The study cohort consisted of 202,542 patients who underwent surgical resection of clinical stage T1-T2 NSCLC (AJCC 7th edition). The 90-day post-operative mortality rate declined significantly during the study period from 4.6% to 2.6% (p < 0.001). During this period, the proportion of facilities that utilized SBRT increased from 3.3% to 77.5% (p < 0.001) and the proportion of patients treated with SBRT increased significantly from 0.7% to 15.4% (p < 0.001). Lower 90-day post-operative mortality rates were observed at facilities with greater than six years of SBRT experience (OR 0.84, CI 0.76-0.94, p = 0.003) and SBRT-to-Surgery volume ratios above 17% (OR 0.85, CI 0.79-0.92, p < 0.001). Additional covariates associated with 90-day mortality included higher surgical volume, geographic region, year of diagnosis, age, sex, race, insurance status, facility type, Charlson-Deyo score, clinical T stage, histology, anatomic location, surgery type, and prior malignancy. Interaction testing between these covariates was negative, demonstrating that higher SBRT Experience and SBRT-to-Surgery volume ratios were independently associated with lower 90-day surgical mortality. Conclusions: Patients who underwent surgery for early-stage NSCLC at facilities with higher SBRT Experience and SBRT-to-Surgery volume ratios had lower rates of post-operative mortality. These findings suggest that the availability of SBRT may be a surrogate for a more comprehensive and safer approach to matching patients to surgery or SBRT. The observation of higher post-operative mortality rates at facilities without an SBRT program deserves further study.
A comparative analysis of mortality between black and white stage III non–small cell lung cancer patients in the United States.
Authors: Elimimian Elizabeth Blessing , Arteta-Bulos Rafael , Liang Hong , Bilani Nadeem , Elson Leah , Saravia Diana , Alley Evan W.
Published: June 2021

8552

Background: Lung cancer remains the leading cause of cancer death in the United States (U.S.). For stage III non-small cell lung cancer (NSCLC), concurrent chemotherapy (CT) plus radiotherapy (RT) within 30 days (CCRT) confers a survival benefit. The proportion of Black and White NSCLC patients not receiving CCRT and their outcomes have not been explored. Methods: Stage III NSCLC in Black and White patients diagnosed between 2004 and 2015 from the U.S. NCDB were included. Those with multiple tumors and who received surgery were excluded. Six groups were analyzed: CCRT (0-30 days between CT and RT), SCRT (31-120 days between CT and RT), RT (only RT), CT (only CT), No-RT-nor-CT (didn’t receive RT nor CT), and other (uncategorized). Univariate, multivariate, and Kaplan-Meier analyses were utilized (p<0.05). Results: A total of 22,459 Black (CCRT 42.3%, SCRT 7.6%, RT 13.8%, CT 15.1%, and No-RT-nor-CT 21.2%) and 138,477 White (CCRT 43.9%, SCRT 7.0%, RT 12.7%, CT 14.9%, and No-RT-nor-CT 21.5%) stage III NSCLCs were analyzed. Male gender and White race were positive predictive factors for receiving CCRT (Table). In Black patients SCRT (HR 1.1; 95% CI 1.04-1.17), RT only (HR 1.2; 95% CI 1.81-1.99), CT only (HR 1.4; 95% CI 1.36-1.49), and No RT or CT (HR 2.6; 95% CI 2.49-2.69) was associated with decreased overall survival (OS) compared to CCRT. In White patients, SCRT (HR, 1.0; 95% CI, 0.99-1.03) did not decrease OS compared to CCRT, whereas RT only (HR 1.8; 95% CI, 1.74-1.80), CT only (HR 1.3; 95% CI, 1.29-1.34), and No RT or CT (HR 2.6; 95% CI, 2.59-2.67) were associated with decreased OS. Median OS with CCRT was 18 months for Black patients, versus 16 months for White patients (p<0.0001). Conclusions: OS was highest when CCRT was given. A lower proportion of Black cases were managed with CCRT, but Black patients benefit more from CCRT and had improved OS than White patients. Despite the known benefits of CT and RT in stage III NSCLC, the second largest management cohort received neither RT nor CT.[Table: see text]
Radical surgery in malignnant pleural mesothelioma (MPM): An analysis of SEER database.
Authors: Wang Qian , Zhang Yaning , Ru Meng , Jiang Changchuan , Tran Jessica , Wisnivesky Juan P. , Veluswamy Rajwanth
Published: June 2021

8554

Background: MPM is an aggressive malignnancy with poor overall prognosis. A combined treatment approach involving radical surgery (RS), radiation (RT) and chemotherapy (CT) provide improved survival compared to systemic treatment alone. Selecting patients who may benefit from RS is challenging. The NCCN guidelines recommend that up to T3N1M0 (Stage IIIA) epithelioid or biphasic MPM should be considered for multimodality therapy incorporating RS. However, the impact of clinical and pathologic features within each histologic subtype of MPM on RS outcomes is unknown. Methods: MPM patients from the SEER 18 program from 2004-2015 were identified. Cox proportional hazard regression models were used to examine the independent contribution of several clinical and pathologic features on overall survival (OS) in patients who received RS vs those that did not. Results: A total of 5,498 MPM patients were identified, of which 531 underwent RS. Overall, RS was associated with improved OS in the multivariate model adjusting for important clinical and pathological characteristics (Table). When stratifying according to histology, epithelioid subtype was linked to improved OS with RS despite of the presence male gender, age > 60 years old, T3, T4 or N2 or above disease; and the OS improved among those who also underwent CT ± RT with RS. Patients with sarcomatoid histology also had OS benefit from RS (HR=0.59, 95%CI: 0.37-0.93), even those that were > 60 years old, but not among those with more advanced disease (T3/4, N2/3). Sarcomatoid patients who received CT ± RT (HR = 0.52, 95%CI: 0.30-0.90) also experienced OS benefit. Among biphasic histology, no OS benefit was found overall (P = 0.11) or within other high-risk clinical features except for those who were treated CT ± RT (HR = 0.64, 95%CI: 0.45-0.90). Conclusions: Our findings demonstrate that the presence of high-risk clinical and pathologic features does not impact OS benefit of RS in epithelioid MPM, however should be considered when deciding on RS in sarcomatoid and biphasic histologies. Poor prognostic histology especially sarcomatoid subtype may experience improved survival with RS if in conjunction with other treatment modalities.[Table: see text]