bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical study of anti-BCMA CAR-T with single-domain antibody as antigen binding domain.
Authors: Han Lu , Gao Quanli , Zhou Keshu , Zhou Jian , Yin Qing-Song , Fang Baijun , Zhu Xing-Hu , Zhang Jishuai , Bao Chaolemeng , Song Yongping 
Published: June 2021

8025 Background: Relapsed/refractory (RR) multiple myeloma (MM), RRMM, remains as an incurable disease and has a 5-year survival rate of nearly 50%. To address the unmet medical need, an autologous CAR-T cell therapy was developed previously with a humanized single-domain antibody (sdAb) targeting BCMA as the antigen binding domain, 4-1BB and CD3ζ as cytoplasmic domain. Methods: An investigator-initiated clinical trial (IIT) was conducted in China to assess the safety and efficacy of the sdAb-based CAR-T. The trail was started in June 2018 and the last patient infused in June 2019. As of 1 February 2021, 34 were treated and followed up. The patients had received multiple lines of prior treatment (including bortezomib, lenalidomide, and others). Following a lymphodepleting regimen of cyclophosphamide (300-600 mg/m2, d-5, -4) and fludarabine (25-30 mg/m2, d-5 to d-3), patients were infused with 2.5-10.0 × 106 CAR+ cells/kg body weight. CAR-T was infused immediately after preparation and quality control performed in all patients except one, who was infused a 10.0 × 106 CAR+ cells/kg dose of frozen cells. Efficacy was assessed based on the IMWG criteria, toxicity was graded by CTCAE 4.02, and CRS grading was based on the grading system by CARTOX working group. Results: All 34 patients had the tumor burden of plasma cells in bone marrow, or M protein or free light chains (FLCs) in serum, 7 patients were accompanied with extramedullary diseases. The efficacy shows the best ORR is 88.2% (30/34), sCR rate is 55.9% (19/34). The mPFS was 12.1 months, several patients shows continuous sCR after 2 years. No obvious correlation between efficacy and dosage were found in three dose groups of 2.5×106 CAR+ cells/kg (6 pts), 5.0×106 CAR+ cells/kg (23 pts) or 10.0×106 CAR+ cells/kg (5 pts). The observed adverse events include thrombocytopenia (≥grade 3, 38.2%), neutropenia (≥grade 3, 44.1%), leukopenia (≥grade 3, 32.4%), lymphopeniPa (≥grade 3, 26.5%), and anemia (≥grade 3, 20.6%). CRS was monitored occurring in 29 patients (any grade, 85.3%, ≥grade 3, 2.9%). Conclusions: Our result demonstrates that the CART employing one humanized sdAb targeting BCMA is safe and efficacious for clinical application. The phase I clinical trial has been initiated in China for searching the RP2D using the cryopreserved CAR-T cells. Clinical trial information: NCT03661554.
Molecular characteristics of EGFR exon 19 deletion subtypes in NSCLC patients.
Authors: Gu Weiquan , Lu Zhongyu , Shi Shulin , Ma Juan , Lu Guanghua , Deng Wanglong , Ding Ran , Bu Fanfeng 
Published: June 2021

8530 Background: EGFR exon 19 deletion mutations are well characterized, known to be activating, and are associated with responses to EGFR tyrosine kinase inhibitors (TKIs). A variety of methods have been developed to identify EGFR mutations. Deletions of EGFR exon 19 are more complex compare to the other because they consist of different subtypes. Methods: In this study, we retrospectively analyzed the different subtypes of EGFR exon 19 deletions using next-generation sequencing(NGS). From May 2019 to December 2020, 3275 patients who were diagnosed with Non-small cell lung cancer (NSCLC)were detected. Results: In this analyzed cohort, the average age of patients was 62 years (range, 24-92 years). Most of the patients were female (61.07%) and were diagnosed with lung adenocarcinoma (82.60%). It is worth noting that the deletions in exon 19 of EGFR were also detected in 35 patients (1.07%) with squamous cell carcinoma and 1 patient (0.03%) with sarcomatoid. The most frequent EGFR exon 19 deletions were delE746-A750 (63.4%), followed by delL747-P753insS (9.7%) and L747-T751 (6.9%). The characteristics of the patients in this study are presented. Significantly, three samples with compound EGFR exon 19 deletions were detected: 1) S1:E746_A750delinsFP+E746_A750del; 2) S2: E746_S752delinsV+L747_P753delinsS; 3) S3:E746_P753delinsVS + L747_P753delinsS. Conclusions: EGFR exon 19 starting at codon 729 to 761, our data showed the deletions occur throughout almost the entire exon 19 amino acid. As our integrated data results, EGFR exon 19 has many different deletions and insertion subtypes could be defined as 79 subtypes. Among those subtypes,70 were complex with an accompanying insertion. The most frequent deletions were starting at E746 and L747. Based on several clinical researches, different deletion subtypes may have significantly different clinical responses after TKI treatment. However, more clinical research is needed to support this finding.
Outcomes of thymic epithelial tumors (TETs) with pleural metastases: Real-world insight from RYTHMIC.
Authors: Maury Jean-Michel , Benitez Jose Carlos , Boucher Marie Eve , Dansin Eric , Kerjouan Mallorie , Bigay-Game Laurence , Pichon Eric , Thillays Francois , Falcoz Pierre-Emmanuel , Svetlana Lyubimova , Oulkhouir Youssef , Fabien Calcagno , Thiberville Luc , Clément Duchene Christelle , Westeel Virginie , Missy Pascale , Thomas Pascal Alexandre , Molina Thierry , Girard Nicolas , Besse Benjamin 
Published: June 2021

8578 Background: TETs are rare and potentially aggressive malignancies with high associated prevalence of autoimmune disorders (AIDs). The pleura is the main metastatic site at relapse, referred as Masaoka-Koga stage (MK) IVa. The benefit of surgical management is unknown, so we have collected outcomes of patients with MK IVa TETs in a large prospective database. Methods: RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network mandated to systematically discuss every case of TETs. The database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in RYTHMIC national or regional tumor boards. We analyzed epidemiologic, clinical and pathological characteristics of patients (pts) with MK IVa TETs. Results: From January 2012 to December 2019, 2909 pts were included in the database, including 182 MK IVa (6.2%). The median age at diagnosis was 63.5 (range 9 to 91). 58/182 (32%) pts reported AIDs, 76% myasthenia gravis. 129/182 pts had synchronous pleural metastasis. 118/182 (65%) tumors were resected, of them 10 (8.4%) had only pericardial metastases. Thymoma (T) B2 rate was 35.6%, B3 17.8% and thymic carcinoma (TC) 13.5%. Induction chemotherapy (CT) was given in 46 (39%) T and 10 (8%) TC with response rate of 50% and 70% respectively. Thymectomy was performed in addition to pleurectomy in 44 pts (37.2%), pericardiectomy in 68 (57.6%), lung resection in 80 (67.8%) or pneumonectomy in 15 (12.7%). Node resection was performed in 57.6% (n = 67), 12 (18%) were positive. The complete resection rate assessed by surgeons was 57% with a median of 15 (0 to 28) resected pleural metastasis. Intrapleural chemotherapy was added for 19 (16%) pts. No mortality was reported 90 days after surgery procedure. Median follow-up was 36 months. Pleural recurrence was seen in 47 (72%) pts. Median disease-free survival (DFS) was 39 vs 16 months in resected vs not resected tumors (p < 0.0001), 5-years overall survival (OS) was 88 vs 66% (p = 0.28), respectively. Risk of relapse decreased by 60% with surgery (HR = 0.4, 95CI (0.25-0.62); p < 0.0001). Conclusions: The prevalence of MK IVa in our cohort was 6.2%. Surgery appears to be a safe and valid option for pts with MK IVa TET at diagnosis.
Response to immune checkpoint inhibition as monotherapy or in combination with chemotherapy in metastatic ROS1-rearranged lung cancers.
Authors: Choudhury Noura J. , Schneider Jaime Laurel , Patil Tejas , Zhu Viola Weijia , Goldman Debra A. , Yang Soo-Ryum , Falcon Christina , Do Andrew , Nie Yunan , Plodkowski Andrew J. , Chaft Jamie E. , Digumarthy Subba , Rekhtman Natasha , Arcila Maria E. , Iasonos Alexia , Ou Sai-Hong Ignatius , Lin Jessica Jiyeong , Drilon Alexander E. 
Published: June 2021

9049 Background: ROS1 fusions are oncogenic drivers in various cancers types, including 1-3% of non-small cell lung cancers (NSCLCs). Immunotherapy approvals for NSCLC include ROS1-rearranged carcinomas, but the activity of immune checkpoint inhibition (ICI) as monotherapy or in combination with chemotherapy (chemo-ICI) therapy, as well as the immunophenotypic characteristics of these tumors, have not been described in a large data set. Methods: In this multi-institutional study, patients with ROS1-rearranged NSCLC were identified retrospectively. Tumor PD-L1 expression and tumor mutational burden (TMB) were assessed as part of routine clinical care. In patients who received ICI monotherapy or chemo-ICI in the metastatic setting, time to treatment discontinuation (TTD) and objective response rate (ORR; RECIST v. 1.1) were calculated. TTD was assessed with Kaplan-Meier methods; patients remaining on treatment were censored at last follow up. Results: 184 patients with ROS1-rearranged NSCLC were identified. Among 146 PD-L1 evaluable cases, PD-L1 expression was < 1% in 60 (41%), 1-49% in 35 (24%) and ≥50% in 51 (35%) tumors. Ninety-two of 100 (92%) TMB-evaluable tumors had < 10 mutations/megabase (mut/Mb). TMB was significantly lower for ROS1-rearranged NSCLCs (n = 97) vs. ROS1-wild type tumors (n = 5,380) evaluated with next-generation sequencing using MSK-IMPACT (median 2.6 vs. 5.9 mut/Mb, p < 0.001). Twenty-eight patients received ICI monotherapy and 11 patients received chemo-ICI. The median TTD was 2.1 months (95% CI: 1.0-4.2; n = 28) for single-agent ICI therapy and 10 months (95% CI: 4.7-14.1; n = 11) for chemo-ICI therapy. The ORR was 13% (2/16 RECIST-evaluable; 95% CI: 2-38%) for ICI monotherapy and 83% (5/6 RECIST-evaluable; 95% CI: 36-100%) for chemo-ICI therapy. There was no difference in PD-L1 tumor expression (p = 0.9) or TMB (p = 0.8) between responders and non-responders and no correlation between PD-L1 tumor expression (rho = 0.16, p = 0.6) or TMB (rho = 0.03, p = 0.9) and maximum change in sum of target lesions. Conclusions: Most ROS1-rearranged NSCLCs have low or no PD-L1 expression and low TMB. The activity of checkpoint inhibitor monotherapy is disappointing in ROS1-driven NSCLC. In contrast, combination chemoimmunotherapy can achieve clinically meaningful activity.
Discontinuation of immune checkpoint inhibitor (ICI) above 18 months of treatment in real-life patients with non-small cell lung cancer (NSCLC): INTEPI, a multicentric retrospective study.
Authors: Bilger Geoffroy , Girard Nicolas , Doubre Helene , Giaj Levra Matteo , Giroux Leprieur Etienne , Giraud Frédérique , Decroisette Chantal , Livartowski Alain , Massiani Marie Ange 
Published: June 2021

9082 Background: The optimal treatment duration of ICIs for patients with NSCLC remains uncertain. In phase 3 clinical trials, treatment continued for two years or until disease progression, and results from CheckMate 153 trial suggest to continue beyond one year. Real life data are missing. Methods: This multi-centric retrospective study presents data on real-life patients who discontinued treatment after at least 18 months of ICI monotherapy, their tumour being still controlled. Their characteristics, the causes of discontinuation of ICI, and their outcome are described. Results: Between July 2015 and May 2018, 107 patients had their tumour controlled after at least 18 months of treatment. Among them, 54 (50%) patients discontinued ICI: 76% male, median age 63, 91% PS 0-1, 54% adenocarcinoma, 20% with brain metastases, PD-L1 expression level available for 18 (33%) patients (2 < 1%, 8 btw 1-50% and 8 > 50%), 93% treated after 1st line. The median duration of treatment was 26 months. Treatment was stopped by choice of the prescriber and toxicity in 46% and 22% respectively. With a median follow up of 21 months from ICI discontinuation, 18 (33%) patients had a tumor progression with a median time of 10 months (2-33). From discontinuation, overall survival (OS) and progression free survival (PFS) were 90% and 71% respectively at 12 months and 84% and 63% respectively at 24 months. Duration of disease control after ICI cessation seemed to be correlated to the best tumor response at treatment discontinuation, with a PFS rates at 12 months of 73% for complete response (CR n = 11), 77% for partial response (PR n = 37), 22% for patients with stable disease (SD n = 6), 80% for CR and/or complete metabolic response with 18F-FDG PET/CT (CMR) and 65% for others. Fourteen patients out of the 18 in the relapse group received a subsequent treatment : 7 were retreated with ICI (with best response 14% PR and 86% SD) and 5 received a localized therapy with 60% CR. Conclusions: Our study in real life provides new insight into the long-term outcomes of patients treated with ICI for at least 18 months before discontinuation in the absence of PD. CR and CMR with FDG-PET before therapy discontinuation may be a positive factor for a prolonged disease control upon discontinuation.
Checkpoint inhibition in immunosuppressed or immunocompromised patients with advanced cutaneous squamous cell carcinoma (CSCC): Data from prospective CemiplimAb-rwlc Survivorship and Epidemiology (C.A.S.E.) study.
Authors: Rabinowits Guilherme , Park Soo J , Ellison David M. , Worden Francis P. , Gentry Rhonda W. , Strasswimmer John , Venna Suraj S. , Migden Michael Robert , Chandra Sunandana , Ruiz Emily S. , Mehta Nikita , Zhang Haixin Raymond , McGinniss Jennifer , Desai Jigar 
Published: June 2021

9547 Background: Immunosuppressed and/or immunocompromised patients are at increased risk for solid tumors and cutaneous malignancies. Limited data exist on the safety and effectiveness of immune checkpoint inhibitors (ICIs) in these patients because they are frequently excluded from clinical trials. Here, we describe the safety and effectiveness results from the initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC enrolled in the C.A.S.E. study (NCT03836105). Methods: C.A.S.E. is a prospective, real-world, multi-center, longitudinal study evaluating the effectiveness, safety, quality of life, and survivorship in patients with advanced CSCC treated with cemiplimab. Patients received cemiplimab 350 mg intravenously every 3 weeks per routine standard of care. Patient demographics, disease characteristics, immunosuppression, and relevant medical history were collected. Immunosuppressive regimens varied amongst patients. Investigator assessment of objective response rate (ORR), safety, and tolerability was conducted. Data from 26 immunosuppressed and/or immunocompromised patients with advanced CSCC treated with cemiplimab are presented. Recruitment is ongoing. Results: As of November 17, 2020, 121 patients were enrolled in the C.A.S.E. study, of which 26 patients (median age: 74 years [IQR: 71-84]; 85% male; 89% Caucasian) were designated as immunocompromised or immunosuppressed due to a history of solid organ transplant (n = 6), autoimmune disorder (n = 11), or hematologic malignancy (n = 9). Median duration of cemiplimab exposure was 14 months (IQR: 9.1–42, range: 0, 67). Among 19 immunocompromised or immunosuppressed patients who enrolled in C.A.S.E. prior to their third dose of cemiplimab, ORR per investigator assessment was 47% (95% CI: 24–71); 1 (5%) patient had complete response; 8 (42%) had partial response. One patient had a treatment-related serious adverse reaction of organ transplant rejection. One (3.8%) patient discontinued treatment due to increased alanine aminotransferase (not treatment-related). Immune-related AEs (irAEs) occurred in 23% of patients. No treatment-related AEs led to death. Conclusions: The safety, tolerability, and effectiveness of cemiplimab in this initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC appear to be consistent with those observed in clinical trials that excluded these patients. Further follow-up and additional data would add to our general understanding of safety and effectiveness of anti-PD1 therapy in immunocompromised and/or immunosuppressed patient populations overall. Clinical trial information: NCT03836105.
Use of strain rate imaging for early detection of epirubicin-induced cardiotoxicity in patients with breast cancer.
Authors: Michalaki Vasiliki , Koutroulis George , Kontis Ioannis , Dafnios Nikolaos , Tiniakos Dina , Papadimitriou Christos 
Published: June 2021

e12531 Background: Although epirubicin has improved outcome in breast cancer (BC) patients, its application is limited by its cardiotoxicity . Assessment of left ventricular (LV) ejection fraction (EF) is performed to demonstrate cardiac dysfunction. Changes in cardiac function induced by this therapy, however, are difficult to quantitate by conventional echocacardiography. Tissue Doppler myocardial imaging (TDI) derived wall motion velocity, and strain rate (SR) have been shown to sensitively quantify abnormalities in cardiac function. The aim of this study was to determine if sensitive indices of LV dysfunction, would be useful for addressing the early detection of cardiotoxic side effects of epirubicin. Methods: BC patients (N = 45 median age 60.2years) without cardiovascular risk factors were prospectively included. All patients received epirubicin. Twenty patients received further trastuzumab. Conventional and TDI echocardiography were obtained at baseline , every 2cycles of treatment and 3 months after chemotherapy. Segmental peak systolic longitudinal and radial velocity, SR and strain, were measured. Results: at baseline, median LV-EF was > 55 %. There was no overall change in LV dimensions, EF and peak systolic velocity. In contrast, a significant reduction in longitudinal and radial SR and strain was found after 3 cycles (longitudinal strain -10.2% +/- 1.3 % vs baseline 22 +/- 4.1 %, P = .001; radial strain 26.1% +/-4,2% vs baseline 47.3% +/- 9.2 %, P < .001). Changes in radial strain appeared earlier and were more pronounced than longitudinal strain. Conclusions: In this study we confirm the clinical use of TDI parameters for early detection of epirubicin mediated cardiac dysfunction. TDI detected subtle changes of LV function after 3 cycles of therapy. Use of Strain Rate Imaging detects subclinical LV dysfunction and can predict further changes in EF ,therefore can be used to monitor epirubicin-induced cardiotoxicity.
Tolerance of aromatase inhibitors in post-menopausal patients with early-stage hormone receptor positive (HR+) breast cancer: A real-world retrospective analysis in a large oncotype database.
Authors: Berwick Shana , Zimmerman Brittney Shulman , Hovstadius Sara Malin , Blanter Julia , Moshier Erin , Berkalieva Asem , Berger Natalie S , Jaffer Shabnam , Cascetta Krystal Pauline , Tiersten Amy 
Published: June 2021

e12532 Background: Aromatase inhibitors (AIs) compose the backbone of adjuvant endocrine therapy for early-stage HR+ breast cancer. Prior studies have demonstrated equivalence in efficacy between aromatase inhibitors in current clinical use. Thus choice of aromatase inhibitors is initially influenced by provider patterns and tailored based on adverse side effects. This study retrospectively evaluates the prevalence of intolerance to AIs warranting a change in therapy. Methods: We identified 181 post-menopausal patients with early-stage, HR+ breast cancer within a database of women who underwent oncotype testing at a large, urban medical center, with 167 (92%) receiving an AI. Patients were excluded if they had received chemotherapy. The Kaplan-Meier method was used to estimate median duration of endocrine therapy (ET). The Fisher’s exact test was used to compare proportions of patients requiring a switch in adjuvant AI and the Wilcoxon rank-sum test was used to compare age distributions. Results: Of the patients identified, 153 (90%) had stage IA disease with a median oncotype RS of 19. 167 (92%) patients received an AI as adjuvant therapy. Median duration of endocrine therapy (ET) was 83.5 months, with over 90% of patients on ET more than 5 years. Among the 152 patients with available data on ET interruptions, 52 (34%) patients had a change or interruption in their ET of these 40 (77%) were attributed to a medication side effect. The AI prescribed most frequently as initial therapy was anastrozole 138/165 (84%). 33 (24%) of patients who received anastrozole required a drug switch within the class, (no sig difference based on initial adjuvant therapy; p=0.4281). 12 (7%) patients required a switch from an AI to tamoxifen at some point during therapy. Changes in AI adjuvant therapy were most commonly attributed to joint pains 24 (46%), followed by hot flashes 2 (4%) and weight gain, 2 (4%). There was no statistically significant difference in median age between patients who interrupted ET due to medication side effect or other reason; p=0.2906. Conclusions: This study enforces previous findings that a significant proportion of women require a change in their adjuvant ET, most commonly due to adverse medication effects such as joint pain. The majority of the women in this database were initiated on anastrozole as initial adjuvant ET of whom 24% required a drug switch.[Table: see text]