scholarly journals 294 Evaluation of radiographic response in the intact renal mass (intact-Rmass) to immune checkpoint inhibitor (ICI) combination regimens in patients with metastatic renal cell carcinoma (mRCC)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A318-A318
Author(s):  
Hamid Emamekhoo ◽  
Danubia Hester ◽  
Saqib Abbasi ◽  
Jens Eickhoff ◽  
Tristan Bice ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Renal Mass ◽  
Single Agent ◽  
Disease Response ◽  
Overall Response ◽  
Radiographic Response ◽  
University Of Wisconsin ◽  
Line Therapy ◽  
History Of ◽  
Combination Regimens

BackgroundAs most of the patients previously enrolled in trials had nephrectomy before starting systemic treatment (syst-Rx), the response of the intact-Rmass to novel ICI and tyrosine kinase inhibitor (TKI) combination regimens is not well described.MethodsA retrospective review of 227 patients with mRCC who were treated with ICI (single agent or combinations) in the 1st- or 2nd-line was conducted. Following the appropriate regulatory process, collaborators from 6 US sites collected clinical, pathological, and outcome data via chart review. Overall response was investigator-assessed for all patients with at least one post-treatment scan or evidence of clinical progression after treatment initiation. Overall radiographic response (ORR) represents any radiographic response in the metastatic disease per investigator’s assessment. To accurately assess response in intact-Rmass, 3-dimensional measurement of the intact-Rmass was performed and Rmass volume was calculated at baseline and at the time of best overall response for 1st- and 2nd-line therapy. Radiographic response in intact-Rmass is defined as >30% decrease in the Rmass volume.ResultsMedian age at diagnosis was 62 years, 69% were male, 82% had clear cell histology. 15% and 12% had sarcomatoid and rhabdoid features, respectively. Overall, 82 patients (36%) had a measurable intact-Rmass while receiving syst-Rx. 63 (28%) patients never had a nephrectomy, and 10 (4%) patients had delayed nephrectomy after a good overall response to syst-Rx. 108 (48%) received ICI in 1st-line (88/108 received ipilimumab/nivolumab combination). 91 (40%), and 18 (8%) patients received TKI, or ICI+TKI in 1st-line. 161 (71%) and 86 (38%) of the patients received 2nd-line and 3rd-line therapy, respectively. 104 (46%) received ICI in 2nd-line (75/104 treated with single-agent ICI). 48 (21%), and 4 (2%) patients received TKI, or ICI+TKI in 2nd-line. Radiographic response in intact-Rmass for evaluable patients is summarized in table 1. The highest response rates in intact-Rmass were seen with ICI+TKI combinations. Higher rates of radiographic response in intact-Rmass were seen in patients treated with ICI in 1st-line compared to 2nd-line, possibly related to higher usage of ICI combinations (ipilimumab/nivolumab) in 1st-line. Overall metastatic disease response to different regimens in the 1st-line or 2nd-line was not different based on the history of nephrectomy prior to syst-Rx (table 2).Abstract 294 Table 1Radiographic response (≥30% decrease in volume) in the intact renal massAbstract 294 Table 2Overall radiographic response (ORR) per investigator assessmentConclusionsHigher radiographic response rates in the intact-Rmass were seen in patients treated with ICI+TKI and ICI in the 1st-line. There was no significant difference in overall metastatic disease response to 1st- or 2nd-line treatment based on the history of nephrectomy prior to syst-Rx.Ethics ApprovalEach of the 6 participating centers had their IRB approved protocol for retrospective study and data collection. Data Use Agreements were obtained for each center to share limited data set data with University of Wisconsin - Madison (IRB protocol UW17148 # 2018–0213). Final analysis was performed at University of Wisconsin.Consent not applicable to retrospective studies.

Is First Line Single Agent Rituximab the Best Treatment for Indolent Non-Hodgkin’s Lymphoma? Update of a Multicentric Study Comparing Rituximab vs CNOP vs Rituximab Plus CNOP.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2431-2431 ◽  
Author(s):  
Silvia Rivas-Vera ◽  
Enrique Baez ◽  
Pedro Sobrevilla-Calvo ◽  
Severiano Baltazar ◽  
Francisco Tripp ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Disease Free Survival ◽  
First Line ◽  
Free Survival ◽  
Overall Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Free

Abstract Purpose: To evaluate efficacy, safety, Disease-Free Survival (DFS) and Overall Survival (OS) in patients with indolent non-Hodgkin’s lymphoma (NHL) treated with chemotherapy vs. immunotherapy vs immunochemotherapy as first-line therapy, an up-date report. Methods: Patients with indolent NHL were randomized to receive: (A) Rituximab x 6/w, (B) CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisone) x 6 or (C) R-CNOP x 6, at standard doses. Results: 195 patients were included, 183 are evaluable for OS and toxicity (A:62, B:55 and C:66), 144 are evaluable for overall response rate (ORR) and DFS (A:53, B:41 and C:50). Clinical characteristics: 89 male (45.6%), mean age 59±14 (±SD), 148 (75.9%) in stage (III/IV), without significant differences between groups. Overall Response Rate (CR+PR) was: A: 84.9%, B:83.4% and C:90% (P=0.545). Neutropenia grade 3/4 was more frequent in the chemotherapy groups: A: 4.8%, B: 23.6% and C:18.2% (P=0.001) as it was the infectious toxicity (grade 2/4): A:4.8%, B:5.5% and C:15.2% (P=0.07). DFS at 24 months was: A 68%, B:65% and C:70%, (P=0.93) and the OS was A:87%, B:84% and C:78%. P=0.89. Conclusions: We did not find any important differences, between groups, regarding the Overall Response Rate, Disease Free Survival and Overall Survival at 24 months. However, single agent rituximab was better tolerated, with less toxicity in comparison with the chemotherapy containing groups. Based on these findings, it maybe reasonable to use immunotherapy only, as first-line therapy for patients with indolent NHL.

Ipilimumab and nivolumab (I+N) as first-line treatment of metastatic renal cell carcinoma (mRCC): A real-world review in North West of England, United Kingdom.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 295-295
Author(s):  
Jennifer Allison ◽  
Richard Griffiths ◽  
Tom Waddell ◽  
Manon Rhys Pillai
Keyword(s):  
Median Time ◽  
Metastatic Disease ◽  
Survival Data ◽  
Single Agent ◽  
Comparable Efficacy ◽  
Line Treatment ◽  
First Line ◽  
Disease Response ◽  
North West

295 Background: Ipilimumab and Nivolumab (I+N) is now an established first line option for patients with advanced RCC of intermediate (I) or poor (P) IMDC risk score. In this retrospective review, we review our experience of this combination in two cancer centres in North West England with a focus on immune related adverse events (irAEs) and their impact on the patient pathway. Methods: Treatment naïve mRCC patients starting I+N between May 2019 and July 2020 were identified. Primary outcomes of interest include overall response rate (ORR), the management of irAEs and early survival observations. Results: A total of 69 patients were identified. Median age was 60yr (19-82yr), 77% had clear cell histology. The IMDC risk was 72% I and 28% P. Median follow-up was 11.0 mo (1-22mo). ORR was 45% (CR 9%, PR 36%, SD 28%, PD 23%, NE 4%) Median time to first response was 2.9mo. (1.8- 15.5mo). 10% of patients experienced pseudoprogression. Median PFS and OS are not yet reached with 86% of patients still alive at the time of data cut-off. The majority (75%) of patients completed all 4 doses of I+N. Of the 10% receiving less than 4 doses due to toxicity, 14% continued on single agent N. Overall, 15% discontinued therapy due to toxicity and 28% experienced at least one treatment delay. Any grade irAEs were seen in 74% of patients (G3 35%) with no treatment related deaths. The commonest irAEs were: rash/pruritis 39%; endocrinopathies 30%(G3 7%); diarrhoea 29% (G3 14%); hepatitis 22% (G3 6%); and nephritis 3% (G3 3%). Of the patients developing irAEs, 71% received steroids with 16% requiring additional immunosuppression including infliximab (6%) and mycophenolate mofetil (8%). A third of all patients required admission for irAE management with a total of 37 inpatient episodes across the cohort with a median length of 7 days (1-24). 7% of patients proceeded to surgery for either primary or metastatic disease, which contributed to ongoing disease response in these patients. At the time of data cut-off, 45% of patients were no longer on treatment due to PD (29%), toxicity (15%) or unrelated death (1%). Of those who stopped due to toxicity, 50% subsequently progressed with a median time to progression of 4mo (3-6 mo) and 50% remain on active surveillance with a median follow-up of 7.5mo (1-10). 62% of patients with PD received second line treatment; most frequently, cabozantinib (83%). Conclusions: Our experience of I+N shows comparable efficacy and toxicity profiles to available reports. irAEs requiring intervention are frequent and may be associated with prolonged hospital admission, and patients should be counselled appropriately. Data within mirrors published reports of ongoing responses in a subset of patients who stop treatment due to toxicity and also suggests a possible role for resection of residual or metastatic disease in disease control. Updated survival data will be presented.

Induction Therapy with Idarubicin and Etoposide Combined with Sequential or Concurrent Azacitidine In Patients with High-Risk Acute Myeloid Leukemia: Pilot-Phase of the AMLSG 12-09 Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2184-2184
Author(s):  
Frank G. Rücker ◽  
Stephan Stilgenbauer ◽  
Martin Bommer ◽  
Daniela Späth ◽  
Silja Mack ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Single Agent ◽  
Severe Toxicity ◽  
Overall Response ◽  
History Of ◽  
Acute Myeloid

Abstract Abstract 2184 Background: Treatment outcome in patients with cytogenetically and/or molecularly defined high-risk acute myeloid leukemia (AML) is dismal with low complete remission (CR) rates after intensive induction therapy and 5-year overall survival of about 25% in patients 60 years and younger and far below 5% in patients above the age of 60 years. In younger patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched related or unrelated donors results in significantly better clinical outcome especially if patients are transplanted early in first CR (Schlenk et al., J. Clin. Oncol. 2010, in press). Azacitidine is a demethylating agent showing promising results as a single agent in AML patients with bone marrow blast counts between 20 and 30%. Therefore, the randomized AMLSG 12-09 trial will evaluate the combination of idarubicin/etoposide chemotherapy combined with azacitidine instead of cytarabine as compared to induction with idarubicin/etoposide/cytarabine (ICE) in an attempt to increase CR rates in these high-risk patients. Aim: To evaluate feasibility of the investigational induction therapy with idarubicin and etoposide in combination with sequentially or concurrently administered subcutaneous (sc) azacitidine. Methods: Patients were treated according to the investigational treatment schedules of the AMLSG 12-09 protocol. Patients received idarubicin 12 mg/sqm on days 1, 3 and 5 and etoposide 100 mg/sqm on days 1, 2 and 3 (patients above the age of 65 years received idarubicin 12 mg/sqm and etoposide 100 mg/sqm only on days 1 and 3, respectively). Azacitidine 100 mg/sqm sc was added on days -5 to -1 in 7 patients (schedule A), days 1 to 5 in 6 patients (schedule B), and days 4 to 8 in 5 patients (schedule C). Results: 18 patients have been treated (13 males and 5 females). Median age was 62.5 years (range, 28–76). The cytogenetic and molecular risk profile of the 18 AML was as follows: Eight AML had MDS-related cytogenetic changes (WHO 2008) including five exhibiting a complex karyotype and two had 3q abnormalities; three AML had balanced t(v;11q23), and six exhibited a normal karyotype together with triple negative genotype (NPM1-wt, FLT3-wt and CEBPA-wt). In one case, there were no metaphases available, however molecularly NPM1-wt, FLT3-wt, CEBPA-wt, no core binding factor AML, no t(15;17) and or t(9;11) were present. Median WBC was 4.6/nl (range, 0–6-75/nl). Overall response to induction therapy was CR n=7, partial remission (PR) n=3, refractory disease (RD) n=7 and one patient died during induction therapy (ED). Moreover, two patients with RD achieved CR after additional cycles of single agent azacitidine treatment. Overall response rates (CR and PR) according to treatment schedule were 43% (3/7), 67% (4/6) and 80% (4/5) for schedules A, B and C, respectively. Most common azacitidine-related toxicity was local reactions at injection site not exceeding CTC-grade 2. As expected, fever in neutropenia was the most common severe toxicity (83%). In addition, one patient with history of epilepsy had seizures during induction therapy and one patient with history of Crohn‘s disease had mucositis CTC-grade 3. Allo-HSCT has been performed in three patients and is planned in five. After a median time of 7.5 months, 16 of 18 patients are alive. Conclusion: Azacitidine administered sc can be given safely either sequentially or concurrently in combination with idarubicine/etoposide induction chemotherapy. Response rate of this high-risk population appears promising and the toxicity profile was favorable. The question which schedule is the most effective will be addressed in the randomized AMLSG trial (NCT01180322) Disclosures: Stilgenbauer: Amgen: Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Sanofi Aventis: Research Funding. Döhner: Pfizer: Research Funding. Schlenk: Celgene, Pfizer, Novartis, Cephalon, Amgen: Research Funding.

James C. Knox (1977) Human impacts on Wisconsin stream channels. Annals of the Association of American Geographers 67: 224–244.

2013 ◽  
Vol 37 (3) ◽  
pp. 422-431 ◽  
Author(s):  
William L. Graf
Keyword(s):  
Mississippi River ◽  
Human Impacts ◽  
Professional Community ◽  
River System ◽  
Stream Channels ◽  
Early 19Th Century ◽  
Driftless Area ◽  
University Of Wisconsin ◽  
History Of ◽  
Floodplain Deposits

James C. Knox’s 1977 paper “Human Impacts on Wisconsin Stream Channels,” published in the Annals of the Association of American Geographers, was a key component of a suite of three papers by him defining the response of rivers to the introduction and management of agriculture and to climate change. In this paper he used the Driftless Area of southwest Wisconsin as a laboratory where he could define fluvial responses by their sedimentary signatures in floodplain deposits. Land-use records dating back to the early 19th century along with shorter climate records provided his understanding of the drivers of change. He found that floods increased as an outcome of land-cover change. Upstream tributaries became wider and shallower as coarse deposits limited their adjustments, while main stem channels became narrower and deeper. His paper reflected the influence of his graduate advisor and especially of prominent faculty colleagues at the University of Wisconsin from fields ranging from soils and climatology to geomorphology and history. The paper was the subject of considerable debate in the professional community, but it remains a much-cited example of Knox’s work in unraveling the Quaternary and Holocene history of rivers of the Driftless Area and by extension the upper Mississippi River system.

Radiological manifestations of metastasis to the ovary

2012 ◽  
Vol 65 (7) ◽  
pp. 585-590 ◽  
Author(s):  
Fredric Willmott ◽  
Kader Abdel Allouni ◽  
Andrea Rockall
Keyword(s):  
Ovarian Cancer ◽  
Metastatic Disease ◽  
Early Stage ◽  
Primary Tumour ◽  
High Rate ◽  
Primary Cancer ◽  
Primary Ovarian Cancer ◽  
Radiological Features ◽  
History Of ◽  
Ovarian Lesion

MRI is an effective tool for detection of ovarian neoplastic lesions. However, there are no highly specific radiological features that differentiate primary from metastatic ovarian masses. Histological diagnosis preoperatively is not always possible as there is a risk of disseminating an otherwise early stage primary ovarian cancer. The preoperative diagnosis of an ovarian lesion is therefore heavily dependent on the radiological features. The radiologist must rely on a combination of knowing the natural history of any known primary cancer, together with the radiological features such as bilaterality, mucinous appearance, pseudomyxoma as well as the clinical progress of the primary tumour in order to evaluate and predict the likelihood of metastatic disease. Even if a non-ovarian primary cancer is known, an ovarian mass cannot always be assumed to be a secondary lesion. Some tumours, such as BRAC-positive breast cancer, are known to have a high rate of concomitant primary ovarian cancer. Conversely, other tumours, such as gastric and appendiceal cancer, are known to have a high rate of ovarian metastatic disease. However, histology remains the only true way to determine an ovarian metastasis from a primary lesion.

Association of combined phase I/II study of a novel bicyclic peptide and MMAE conjugate BT8009 in patients with advanced malignancies with Nectin-4 expression.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS2668-TPS2668
Author(s):  
Meredith McKean ◽  
Gerald Steven Falchook ◽  
Johanna C. Bendell ◽  
Babar Bashir ◽  
Neil Palmisiano ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Single Agent ◽  
Pancreatic Head ◽  
Uncontrolled Hypertension ◽  
Clinical Activity ◽  
Highly Active ◽  
History Of ◽  
Cyp3a4 Inhibitors ◽  
Critical Organ ◽  
Peptide Targeting

TPS2668 Background: BT8009 is a Bicycle Toxin Conjugate (BTC), a novel class of chemically synthesized molecules, comprising a bicyclic peptide targeting Nectin-4 tumor antigen, linked to cytotoxin (monomethyl auristatin E [MMAE]) via a valine-citrulline (val-cit) cleavable linker. Nectins (Nectin-1, -2, -3, and -4) and nectin-like molecules (Necl) are Ca2+ independent immunoglobulin-like cell adhesion molecules. Recent studies have shown the importance of Nectin-4 in several human cancers, including lung, ovarian, breast and bladder cancer; however, the precise roles and clinical relevance of Nectin-4 in tumors remain largely unknown. The Nectin-4 targeted enfortumab vedotin, linked to MMAE via a val-cit linker, is highly active in late-stage bladder cancer and demonstrates notable additional clinical activity as a single agent and in combination with pembrolizumab1. Skin toxicities, bone marrow suppression, peripheral neuropathy and diabetes have been associated with enfortumab, with some of these toxicities already noted with MMAE-bearing antibody therapies. We anticipate a similar toxicity profile for BT8009 in clinical studies. BT8009 exhibited a favorable preclinical profile and was effective in a range of cell-derived xenograph tumor models. Methods: Study BT8009-100 (NCT04561362) will evaluate safety and tolerability of weekly and every other week BT8009 administration, alone and in combination with q4w nivolumab. Determination of both a realistic phase 2 dose and a sequence will also be key to further exploration of safety and efficacy signals, along with an early examination of the role of baseline immunohistochemistry-ascertained levels of tumor Nectin-4. Patients will be recruited with advanced solid tumors associated with Nectin-4 expression after exhausting SOC options (i.e., bladder, breast, pancreatic, head and neck, gastric, esophageal and ovarian). Patients must have available tumor tissue, acceptable hematologic and other critical organ function and be willing to participate. Appropriate ethical and regulatory approvals and advice will be in place and adhered to. Exclusion criteria include uncontrolled brain metastases, uncontrolled hypertension, concomitant CYP3A4 inhibitors and significant history of autoimmune disease for the nivolumab cohorts. PK serial collections will be taken on D1 through D15. Radiologic tumor assessments for response per RECIST will be taken every two months. 1. Enfortumab Vedotin. FDA_data. 761137Orig1s000MultiDiscliplineR.pdf (fda.gov). Clinical trial information: NCT04561362.

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