Kooperativer Bibliotheksverbund

In: The Lancet, Elsevier BV, Vol. 400, No. 10363 ( 2022-11), p. 1607-1617

Type of Medium: Online Resource

ISSN: 0140-6736

URL: Article

DOI: 10.1016/S0140-6736(22)01846-3

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2067452-1

detail.hit.zdb_id: 3306-6

detail.hit.zdb_id: 1476593-7

SSG: 5,21

In: British Journal of Surgery, Oxford University Press (OUP), Vol. 110, No. 7 ( 2023-06-12), p. 804-817

Abstract: Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries.

Type of Medium: Online Resource

ISSN: 0007-1323 , 1365-2168

URL: Article

DOI: 10.1093/bjs/znad092

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2023

detail.hit.zdb_id: 2006309-X

In: Diabetes Care, American Diabetes Association, Vol. 45, No. 12 ( 2022-12-01), p. 2991-2998

Abstract: Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD and FIGARO-DKD phase 3 studies. Effects of finerenone on outcomes in patients taking sodium–glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30 to ≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 were randomly assigned to finerenone or placebo; SGLT2is were permitted at any time. Outcomes included cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death) end points, changes in UACR and eGFR, and safety outcomes. RESULTS Among 13,026 patients, 877 (6.7%) received an SGLT2i at baseline and 1,113 (8.5%) initiated one during the trial. For the cardiovascular composite, the hazard ratios (HRs) were 0.87 (95% CI 0.79–0.96) without SGLT2i and 0.67 (95% CI 0.42–1.07) with SGLT2i. For the kidney composite, the HRs were 0.80 (95% CI 0.69–0.92) without SGLT2i and 0.42 (95% CI 0.16–1.08) with SGLT2i. Baseline SGLT2i use did not affect risk reduction for the cardiovascular or kidney composites with finerenone (Pinteraction = 0.46 and 0.29, respectively); neither did SGLT2i use concomitant with study treatment. CONCLUSIONS Benefits of finerenone compared with placebo on cardiorenal outcomes in patients with CKD and type 2 diabetes were observed irrespective of SGLT2i use.

Type of Medium: Online Resource

ISSN: 0149-5992 , 1935-5548

URL: Article

DOI: 10.2337/dc22-0294

Language: English

Publisher: American Diabetes Association

Publication Date: 2022

detail.hit.zdb_id: 1490520-6

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 10424-10426

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-166783

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2463-2463

Abstract: INTRODUCTION: Anaplastic large cell lymphoma, ALK-positive (ALK+ ALCL), is an aggressive CD30 positive T-cell lymphoma. The use of brentuximab vedotin (BV) in the frontline setting has demonstrated improved outcomes. However, data outside of controlled settings such as clinical trials are lacking. Although the overall prognosis of ALK+ ALCL is remarkably better than other T-cell lymphomas, no particular risk factors predictive of early relapse and mortality have been clearly identified. Therefore, we conducted a retrospective review of newly diagnosed ALK+ ALCL managed with systemic therapy and to identify clinico-pathologic characteristics associated with early relapse and mortality. METHODS: We retrospectively analyzed patients with untreated ALK+ ALCL diagnosed between 2002 and 2020 at The University of Texas MD Anderson Cancer Center. The study outcomes were overall survival (OS) and progression-free survival (PFS). The International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PIT) scores were used for risk stratification. The therapy approaches used during the patients' disease process were divided as follow: BV-based therapy (either alone or in combination with chemotherapy); and non-BV-based therapy. Kaplan-Meier and log-rank test were used for survival analysis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios (HR) with a 95% confidence interval (CI). Outcomes with a p-value & lt;0.05 were considered statistically significant. RESULTS: We identified 117 patients, 11 were excluded due to incomplete data. In the remaining 106 patients, the median age at diagnosis was 39 years (range 23-81, 83% & lt;60 years) with a male predominance (57%). Most patients (90%) had ECOG performance status 0-1; 41% had elevated serum lactate dehydrogenase level; 68% had stage III/IV; 15% had bone marrow involvement; 85% had IPI score 0-2 (i.e., low, low-intermediate risk); and 84% had PIT score 0-1 (i.e., low, low-intermediate risk). Table 1 summarizes the clinical features according to the therapy used. BV-based therapy was given to 29% (n=31/106) of patients. Among the 99 patients evaluable for response, overall response (OR) rate to first-line treatment was 96% (95% CI: 90-99%) with complete response (CR) rate of 86.7% (95% CI: 78.6-92.8%). There were no differences in responses between BV and non-BV regimens (Table 1). With a median follow up of 50 months (95% CI: 34.3-65 months), the median OS on the entire cohort was not reached and 4-year OS rate was 85% (95% CI: 78-93%); the median PFS to first-line therapy and 4-year PFS rate were 84.6 months (95% CI: 76.1-not reached) and 66% (95% CI: 56-77%), respectively (Figure 1). In the univariate analysis, frontline BV showed a significant improvement in PFS (5-years 82% versus 57%; p=0.038) but no OS (Table 2, Figure 2). Bone marrow involvement was associated with worse OS (p=0.002) and PFS (p=0.031) (Table 2, Figure 3). Second-line therapy (either with BV or non-BV regimens) was reported in 39 patients; OR rate was 82.1% (95% CI: 66.5-92.5%) with CR rate of 74.4% (95% CI: 57.9-87.0%). However, median PFS (17.5 months) and 4-year PFS rate (41%) were significantly shorter than with first-line therapy. Progression after first- and second-line therapy was seen in 47% and 61% of patients, respectively. Stem cell transplantation was performed in 28% of patients (n=27/95) upon first relapse (autologous n=23; allogeneic n=4 [two upon progression from autologous transplant]); outcomes with this approach will be presented at the meeting. CONCLUSION: This large cohort of ALK+ ALCL patients was characterized by younger age, good performance status, advanced disease, and low- to intermediate-risk IPI/PIT scores. Although CR rates to first-line therapy were over 85% with both BV- and non-BV-based regimens, only frontline BV-based regimens conferred improved PFS. Furthermore, bone marrow involvement was associated to shorter OS and PFS. Response rates after salvage therapy were high, but with shorter PFS. In conclusion, this study suggest the addition of BV as the preferred regimen in the management of ALK+ ALCL; a more aggressive approach might be considered to those deemed as high risk for early mortality and relapse (i.e., bone marrow involvement). Further analysis with pathologic and molecular studies are ongoing and results will be reported at the meeting. Figure 1 Figure 1. Disclosures Jain: Lilly: Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy. Chihara: Astrazeneca: Honoraria. Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Samaniego: Arog: Research Funding; Imbrium: Membership on an entity's Board of Directors or advisory committees. Ahmed: Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding; Xencor: Research Funding; Merck: Research Funding. Fowler: Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company. Nastoupil: Takeda: Honoraria, Other: DSMC, Research Funding; Caribou Biosciences: Research Funding; Janssen: Honoraria, Research Funding; Gilead/Kite: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; MorphoSys: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria; Epizyme: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC. Hosing: Nkarta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Vega: CRISPR Therapeutics and Geron: Research Funding; i3Health, Elsevier, America Registry of Pathology, Congressionally Directed Medical Research Program, and the Society of Hematology Oncology: Research Funding. Pinnix: Merck Inc: Research Funding. Wang: OMI: Honoraria; VelosBio: Consultancy, Research Funding; The First Afflicted Hospital of Zhejiang University: Honoraria; CAHON: Honoraria; BioInvent: Research Funding; Dava Oncology: Honoraria; CStone: Consultancy; Kite Pharma: Consultancy, Honoraria, Research Funding; InnoCare: Consultancy, Research Funding; Imedex: Honoraria; Lilly: Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Moffit Cancer Center: Honoraria; Epizyme: Consultancy, Honoraria; Hebei Cancer Prevention Federation: Honoraria; Clinical Care Options: Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Newbridge Pharmaceuticals: Honoraria; Genentech: Consultancy; Chinese Medical Association: Honoraria; Molecular Templates: Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; BGICS: Honoraria; Celgene: Research Funding; Bayer Healthcare: Consultancy; Mumbai Hematology Group: Honoraria; Physicians Education Resources (PER): Honoraria; Scripps: Honoraria; Pharmacyclics: Consultancy, Research Funding; Juno: Consultancy, Research Funding; Oncternal: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Loxo Oncology: Consultancy, Research Funding; Anticancer Association: Honoraria; Acerta Pharma: Consultancy, Honoraria, Research Funding. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria. Flowers: Kite: Research Funding; BeiGene: Consultancy; EMD: Research Funding; Janssen: Research Funding; AbbVie: Consultancy, Research Funding; Xencor: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Celgene: Consultancy, Research Funding; Denovo: Consultancy; TG Therapeutics: Research Funding; Biopharma: Consultancy; Takeda: Research Funding; Ziopharm: Research Funding; Sanofi: Research Funding; Genentech/Roche: Consultancy, Research Funding; Genmab: Consultancy; Gilead: Consultancy, Research Funding; Epizyme, Inc.: Consultancy; National Cancer Institute: Research Funding; Karyopharm: Consultancy; Pharmacyclics/Janssen: Consultancy; SeaGen: Consultancy; Bayer: Consultancy, Research Funding; Guardant: Research Funding; Spectrum: Consultancy; Morphosys: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; 4D: Research Funding; Iovance: Research Funding; Nektar: Research Funding; Cellectis: Research Funding; Acerta: Research Funding; Amgen: Research Funding; Allogene: Research Funding; Adaptimmune: Research Funding; Pharmacyclics: Research Funding. Iyer: CRISPRX: Research Funding; Seattle Genetics: Research Funding; Rhizen: Research Funding; Merck: Research Funding; Legend: Research Funding; Innate: Research Funding; Spectrum: Research Funding; Trillium: Research Funding; Astra Zeneca: Research Funding; Yingli: Research Funding; Cyclacel: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-150798

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: British Journal of Surgery, Oxford University Press (OUP), Vol. 108, No. 11 ( 2021-11-11), p. 1274-1292

Abstract: To support the global restart of elective surgery, data from an international prospective cohort study of 8492 patients (69 countries) was analysed using artificial intelligence (machine learning techniques) to develop a predictive score for mortality in surgical patients with SARS-CoV-2. We found that patient rather than operation factors were the best predictors and used these to create the COVIDsurg Mortality Score (https://covidsurgrisk.app). Our data demonstrates that it is safe to restart a wide range of surgical services for selected patients.

Type of Medium: Online Resource

ISSN: 0007-1323 , 1365-2168

URL: Article

DOI: 10.1093/bjs/znab183

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2021

detail.hit.zdb_id: 2006309-X

In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e6330214-

Type of Medium: Online Resource

ISSN: 2572-9241

URL: Article

DOI: 10.1097/01.HS9.0000971264.63302.14

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2023

detail.hit.zdb_id: 2922183-3

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 12005-12007

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-170750

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1448-1448

Abstract: BACKGROUND: T-cell/histiocyte-rich large B-cell lymphoma (T/HRLBCL) is an aggressive morphological variant of diffuse large B cell lymphoma (DLBCL), which often presents with advanced stage disease, extra-nodal involvement, an association with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and has poor outcomes compared to patients (pts) with other DLBCL subtypes. METHODS: We conducted a retrospective, single institution study of pts with newly diagnosed T/HRLBCL and reviewed demographic variables, clinical and pathological characteristics, treatment patterns and outcomes. Pts who were treated/ referred to MD Anderson Cancer Center from 2005-2020 were included in the analysis. We excluded cases without pathologic confirmation by a hematopathologist, missing treatment information, lack of appropriate follow up, or previous treatment with anthracycline containing chemotherapy for unrelated diagnosis. Fisher's exact test or Chi-square test was used to evaluate the association between two categorical variables, Kaplan-Meier method used to estimate the time-to-event endpoints including progression free survival (PFS) and overall survival (OS). RESULTS: A total of 172 patients were reviewed, 65 pts were excluded due to aforementioned reasons. A total of 107 newly diagnosed patients met morphological diagnostic criteria. Seventy four pts (70%) were less than 60 years of age at diagnosis with median age of 49 (18-89 years). Seventy two were male (68%) and 37 pts (34%) had documented NLPHL prior to or at the time of T/HRLBCL diagnosis. Ninety pts (89%) were diagnosed with advance stage disease (stage 3/4) with 59pts (55%) with ≥ 1 extra nodal site. Thirty-seven pts (35%) had associated splenomegaly and/or FDG avid splenic involvement. Common extra nodal sites included bone (26%), bone marrow (19%) and liver (17%). On univariate analysis for survival outcomes, there was not a statistical significant association with any of the following: age, gender, association with NLPHL, presence of B symptoms, performance status, elevated lactate dehydrogenase, extra nodal sites, spleen involvement/ splenomegaly, involvement of liver, and type of front-line treatment. Majority of patients (73%) received front line treatment with R-CHOP, followed by Dose Adjusted R-EPOCH (15%) and other regimens in 11%. Central nervous system prophylactic therapy was given in 24 pts (intrathecal) and 3 pts (high dose methotrexate). One pt had an autologous stem cell transplant consolidation as part of frontline treatment. Seventy (69%) pts achieved complete response (CR), with an overall response rate of 75%, and 25 pts progressed on frontline treatment. Complete remission rates were higher with R-EPOCH (81%) than RCHOP (70%) (p=0.57), with 2 year PFS to first line treatment at 38% and 46% respectively (P=0.20). In the whole cohort, 2-year PFS was 48% and 2-year OS was 83%. Of the 53 patients who relapsed, 48 patients received salvage chemotherapy, 26 pts went on to receive high dose chemotherapy and autologous transplant, and only 4 patients relapsed after transplant. Three patients in the whole cohort who received CD19 CAR-T and all 3 had disease progression. Conclusions: This study demonstrates the generally poor outcomes in pts with T/HRLBCL despite the use of monoclonal antibodies and intensive cytotoxic therapies. T/HRLBCL remains a high unmet need for novel therapies. Figure 1 Figure 1. Disclosures Fowler: Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company. Steiner: BMS: Research Funding; Rafael Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding. Strati: Astrazeneca-Acerta: Research Funding; Roche-Genentech: Consultancy. Chihara: Astrazeneca: Honoraria. Jain: kite: Consultancy; Lilly: Consultancy. Flowers: Morphosys: Research Funding; Ziopharm: Research Funding; Pfizer: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Acerta: Research Funding; Kite: Research Funding; EMD: Research Funding; Xencor: Research Funding; Cellectis: Research Funding; SeaGen: Consultancy; BeiGene: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Spectrum: Consultancy; Genentech/Roche: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Allogene: Research Funding; Denovo: Consultancy; Biopharma: Consultancy; Epizyme, Inc.: Consultancy; Genmab: Consultancy; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; Pharmacyclics/Janssen: Consultancy; Nektar: Research Funding; Amgen: Research Funding; Adaptimmune: Research Funding; National Cancer Institute: Research Funding; Guardant: Research Funding; Sanofi: Research Funding; Novartis: Research Funding; TG Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Iovance: Research Funding; 4D: Research Funding; Bayer: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pharmacyclics: Research Funding. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria. Nastoupil: IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC; Epizyme: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; ADC Therapeutics: Honoraria; TG Therapeutics: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; MorphoSys: Honoraria; Gilead/Kite: Honoraria, Research Funding; Bayer: Honoraria; Genentech: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Janssen: Honoraria, Research Funding. Wang: Celgene: Research Funding; Loxo Oncology: Consultancy, Research Funding; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Clinical Care Options: Honoraria; VelosBio: Consultancy, Research Funding; BioInvent: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Anticancer Association: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; CAHON: Honoraria; Moffit Cancer Center: Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; Mumbai Hematology Group: Honoraria; Epizyme: Consultancy, Honoraria; Hebei Cancer Prevention Federation: Honoraria; Chinese Medical Association: Honoraria; Dava Oncology: Honoraria; Acerta Pharma: Consultancy, Honoraria, Research Funding; Molecular Templates: Research Funding; Kite Pharma: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Lilly: Research Funding; Newbridge Pharmaceuticals: Honoraria; OMI: Honoraria; Physicians Education Resources (PER): Honoraria; Pharmacyclics: Consultancy, Research Funding; Scripps: Honoraria; The First Afflicted Hospital of Zhejiang University: Honoraria; Oncternal: Consultancy, Research Funding; BGICS: Honoraria; Bayer Healthcare: Consultancy; CStone: Consultancy; DTRM Biopharma (Cayman) Limited: Consultancy; Genentech: Consultancy; InnoCare: Consultancy, Research Funding; Juno: Consultancy, Research Funding. Vega: i3Health, Elsevier, America Registry of Pathology, Congressionally Directed Medical Research Program, and the Society of Hematology Oncology: Research Funding; CRISPR Therapeutics and Geron: Research Funding. Iyer: CRISPRX: Research Funding; Seattle Genetics: Research Funding; Rhizen: Research Funding; Merck: Research Funding; Legend: Research Funding; Innate: Research Funding; Spectrum: Research Funding; Trillium: Research Funding; Astra Zeneca: Research Funding; Yingli: Research Funding; Cyclacel: Research Funding. Westin: Morphosys: Research Funding; 47 Inc: Research Funding; AstraZeneca: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Curis: Research Funding; Genentech: Consultancy, Research Funding; Iksuda Therapeutics: Consultancy; Umoja: Consultancy; ADC Therapeutics: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-154035

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3526-3526

Abstract: Introduction: The standard of care for patients with stage IE indolent B-cell lymphoma (BCL) of the ocular adnexa is external beam radiotherapy (RT) to 24-30 Gy. Even with these moderate doses, ocular morbidity is common. Indolent BCL is radiosensitive, with reports of complete response (CR) to 4 Gy. We sought to evaluate the efficacy of a response adapted strategy for the treatment of orbital indolent BCL with upfront ultra-low dose (ULD) orbital RT (4 Gy) and an additional 20 Gy for incomplete responders. Methods: We conducted a phase II single arm study in patients with stage I-IV indolent BCL involving the orbit. Patients were treated with ULD RT to 4 Gy in 2 fractions to the affected orbit(s). Response was assessed clinically and/or radiographically 3 months after ULD RT. Patients with a CR were observed. Patients without CR were evaluated in 3-4 month intervals and offered an additional 20 Gy if they had two consecutive visits with no tumor reduction. The primary endpoint was local control (LC) within the RT field defined from the last day of RT. Secondary endpoints included CR rate, freedom from distant relapse (for stage I patients) and overall survival. We hypothesized that this response adapted strategy would yield equivalent LC to that of standard therapy (24 Gy up front). CR was defined as clinical and/or radiographic resolution of orbital disease. In patients with pre-therapy PET-CT avid disease, CR was defined as a 5PS of 1-3 with or without a residual mass. Partial response (PR) was defined as a decrease in clinical or radiographic disease burden by ≥50% by sum of the disease parameters. Minimal response (MR) was defined as & lt; 50% in orbital disease burden. Stable disease (SD) and progressive disease (PD) were defined as no change or increasing disease, respectively. Results: Between July 2015 and January 2021, 51 patients were enrolled. The median age was 63 years (range 29-88); 62% were female (n=31). Diagnoses included MALT lymphoma (65%, n=33), follicular lymphoma (FL) (24%, n=12), and unclassified low-grade BCL (12%, n=6). Thirty-two patients (63%) had disease confined to one or both orbits at enrollment (stage I); 37 (73%) had newly diagnosed, untreated lymphoma. All patients received 4 Gy in 2 fractions to the affected orbit(s) (bilateral, n=8). Treatment was well tolerated without grade 3 or higher toxicity. One patient did not return for follow up. For 50 evaluable patients, at a median follow up of 21.9 months (95% CI 16.2 - 27.6), 44 patients achieved a CR to ULD therapy (88%) at a median time of 3.4 months (IQR 3, 3.9). Nine patients (20%) had residual disease at the first follow up visit but subsequently had resolution of orbital lymphoma in future follow up. No patient who experienced CR to ULD RT had an in-field orbital relapse (freedom from local relapse rate = 100%, Figure 1a). At the time of follow up #3, 7 patients had not experienced CR and had evidence of disease (Figure 2). Among these 7 patients, 1 achieved CR with continued observation (without intervening therapy) and 2 are being observed with stable disease. Ultimately 4 patients were recommended additional RT to 20 Gy; two patients received the recommended RT, one refused additional RT, one was treated with rituximab for systemic disease progression. After an additional 20 Gy, one patient has stable disease at 21 months and the other patient has pending follow-up. Of the 50 evaluable patients, 31 had stage I disease (MALT = 25, FL=4, low grade BCL =2) that was either untreated (n=25) or had relapsed or progressed in the orbit (n=6) after rituximab (n=2), surgical excision (n=2) or contralateral RT (n=2). Twenty-eight stage I patients (90%) had a CR to ULD RT; of these, the 2-year freedom from local recurrence rate was 100% (Figure 1b) and the freedom from distant relapse rate was 87% (Figure 1b). Distant relapses in the mediastinum, lung, contralateral orbit and mesentery were salvaged successfully with bendamustine/rituximab, rituximab, contralateral 4 Gy orbital RT and rituximab, respectively. None of the 3 patients that did not completely respond to ULD RT experienced distant relapse. Conclusions: In the first prospective study evaluating this novel approach of response adapted ULD orbital RT, orbital outcomes were compelling with minimal toxicity. Additional follow up is required to evaluate long term LC. Response adapted ULD orbital RT is an effective and promising strategy for the definitive management of indolent BCL of the ocular adnexa. Figure 1 Figure 1. Disclosures Pinnix: Merck Inc: Research Funding. Nastoupil: Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; MorphoSys: Honoraria; Gilead/Kite: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Epizyme: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; IGM Biosciences: Research Funding; TG Therapeutics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Denovo Pharma: Other: DSMC; ADC Therapeutics: Honoraria; Bayer: Honoraria; Caribou Biosciences: Research Funding. Strati: Astrazeneca-Acerta: Research Funding; Roche-Genentech: Consultancy. Ahmed: Seagen: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Xencor: Research Funding. Steiner: Rafael Pharmaceuticals: Research Funding; BMS: Research Funding; Seattle Genetics: Research Funding. Jain: kite: Consultancy; Lilly: Consultancy. Westin: Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Umoja: Consultancy; Iksuda Therapeutics: Consultancy; Curis: Research Funding; Morphosys: Research Funding; 47 Inc: Research Funding. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees. Wang: BioInvent: Research Funding; Celgene: Research Funding; Molecular Templates: Research Funding; Lilly: Research Funding; VelosBio: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Oncternal: Consultancy, Research Funding; Loxo Oncology: Consultancy, Research Funding; Juno: Consultancy, Research Funding; InnoCare: Consultancy, Research Funding; Genentech: Consultancy; DTRM Biopharma (Cayman) Limited: Consultancy; CStone: Consultancy; Bayer Healthcare: Consultancy; BGICS: Honoraria; The First Afflicted Hospital of Zhejiang University: Honoraria; Scripps: Honoraria; Physicians Education Resources (PER): Honoraria; OMI: Honoraria; Newbridge Pharmaceuticals: Honoraria; Mumbai Hematology Group: Honoraria; Moffit Cancer Center: Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Hebei Cancer Prevention Federation: Honoraria; Epizyme: Consultancy, Honoraria; Dava Oncology: Honoraria; Clinical Care Options: Honoraria; Chinese Medical Association: Honoraria; CAHON: Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Anticancer Association: Honoraria; Acerta Pharma: Consultancy, Honoraria, Research Funding. Samaniego: Arog: Research Funding; Imbrium: Membership on an entity's Board of Directors or advisory committees. Fowler: BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company; Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Flowers: Karyopharm: Consultancy; SeaGen: Consultancy; Genentech/Roche: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Acerta: Research Funding; Biopharma: Consultancy; Genmab: Consultancy; 4D: Research Funding; Denovo: Consultancy; Spectrum: Consultancy; BeiGene: Consultancy; Celgene: Consultancy, Research Funding; Pharmacyclics/Janssen: Consultancy; Epizyme, Inc.: Consultancy; Bayer: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Adaptimmune: Research Funding; Allogene: Research Funding; Amgen: Research Funding; Cellectis: Research Funding; EMD: Research Funding; Guardant: Research Funding; Iovance: Research Funding; Janssen: Research Funding; Kite: Research Funding; Morphosys: Research Funding; Nektar: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Ziopharm: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Pharmacyclics: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-154172

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7