Phase II Study of Thymglobulin, Cyclosporin, and G-CSF for the Initial Treatment of Aplastic Anemia and Low Risk Myelodysplastic Syndrome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4830-4830
Author(s):  
Farhad Ravandi-Kashani ◽  
Zeev Estrov ◽  
Alessandra Ferrajoli ◽  
Gautam Borthakur ◽  
Miloslav Beran ◽  
...  
Keyword(s):  
Side Effects ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Oral Prednisone ◽  
Disease Process ◽  
Low Risk ◽  
First Line Therapy ◽  
Unsuccessful Treatment ◽  
Life Threatening ◽  
Grade 3

Abstract Standard therapy of aplastic anemia (AA) involves the use of equine anti-thymocyte globulin (ATG) in combination with cyclosporine. Hematological responses occur in 40% to 50% of patients treated with ATG alone. The addition of cyclosporine to ATG has improved response and survival; response rates have been up to 65%, and the 5-year survival rate in the responding patients has been over 80%. Several lines of observation have also implicated an autoimmune mechanism in at least a subset of patients with myelodysplastic syndrome (MDS) whose disease process may overlap AA. The rationale for treating refractory or relapsing patients with ATG from a different animal has been the lower risk of potentially life-threatening allergic reactions. In a recent study, most patients who received rabbit ATG (Thymoglobulin) after unsuccessful treatment with ATG became transfusion independent (Di bonna E, Br J Haematol, 1999). Another study has reported high responses to Thymoglobulin in patients with relapsed AA (Scheinberg P, Br J Haematol, 2006). We are conducting a clinical trial of Thymoglobulin in combination with cyclosporin and GCSF in the first line therapy of patients with AA or low-risk MDS. Patients receive Thymoglobulin 3.5 or 2.5 (if they were 55 years or older) mg/kg/day IV for 4 days, methyl prednisone 1 mg/kg/day IV for 4 days followed by a tapering dose of oral prednisone, cyclosporine 5 mg/kg orally, and G-CSF 5 μg/kg daily for up to 3 months at the discretion of the treating physician. All patients receive prophylactic broad-spectrum antibiotics. We have enrolled 13 patients in the study including 7 patients with AA and 6 patients with MDS. The median age for AA patients was 61 years (range 45 – 73 years), and for MDS patients 60 years (range, 41 – 71 years). The median absolute neutrophil count (ANC) for AA patients was 0.74 × 109/L (range, 0.1 – 1.0 × 109/L) and for MDS patients 2.0 × 109/L (range, 1.1 – 8.1 × 109/L). The median Hgb for AA patients was 6.9 g/dL (range, 3.9 – 7.9 g/dL) and for MDS patients 8.1 g/dL (range 6.4 – 10.7 g/dL). The median platelet count for AA patients was 8 × 109/L (range, 0 – 153 × 109/L) and for MDS patients 10 × 109/L (range, 6 – 16 × 109/L). Flow cytometry for a PNH clone was negative in all patients. Seven patients (4 AA, 3 MDS) were positive for HLA-DR15. So far, 6 patients with AA have responded including 3 CRs, 2 PRs and 1 HI. One patient with MDS had a PR. Toxicity has been acceptable with no grade 3 or 4 side effects. Other side effects (grade 1 and 2) included infusion-related reactions, hypomagnesemia, elevation of serum creatinine, and hyperbilirubinemia. We conclude that Thymoglobulin can be administered safely in combination with cyclosporin and GCSF to treat patients with untreated AA and MDS.

Updated Results of Combination Cytokine Immunotherapy In the Treatment of Aplastic Anemia and Myelodysplastic Syndrome (MDS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2920-2920 ◽  
Author(s):  
Tapan Kadia ◽  
Farhad Ravandi ◽  
Guillermo Garcia-Manero ◽  
Elias Jabbour ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Supportive Care ◽  
Aplastic Anemia ◽  
Oral Prednisone ◽  
Disease Free Survival ◽  
International Prognostic Scoring System ◽  
Serious Infections ◽  
Common Grade ◽  
Infusion Reactions ◽  
Grade 3

Abstract Abstract 2920 Immunosuppressive therapy using antithymocyte globulin (ATG) and cyclosporine has been successfully used in the treatment of cytopenias in patients (pts) with severe aplastic anemia (AA). Laboratory and clinical data suggest that dysregulated immune mechanisms may also contribute to the pathogenesis of ineffective hematopoiesis in some subsets of early MDS and result in cytopenias. Rabbit ATG (rATG) is active and well tolerated in pts have recurrent/persistent disease after treatment with equine ATG. Here we present our updated results with a combination of rATG, cyclosporine, prednisone, and G-CSF in pts with aplastic anemia or myelodysplastic syndrome. This is a single-arm phase II study evaluating the efficacy and safety of the following combination in pts with aplastic anemia and low or intermediate-1 risk MDS (by the international prognostic scoring system) : rATG 3.5 mg/kg/day (or 2.5 mg/kg/day for age ≥ 55 yrs) intravenously (IV) for 5 days, methylprednisone 1mg/kg/day IV daily for 5 days (given prior to each dose of ATG), followed by oral prednisone tapered off over 1 month, G-CSF (filgrastim daily or pegfilgrastim every 2 weeks) subcutaneously for up to 3 months, and cyclosporine (5 mg/kg) daily for up to 6 months. Dose reductions or interruptions for toxicities were allowed at the discretion of the treating physician. Responses were assessed at 3 months after initiating therapy. Of the 51 pts enrolled, 46 have received treatment including 23 (50%) pts with AA and 23 (50%) pts with MDS. The median age overall was 60 yrs (range, 19–82), 54 (19-82) in the AA and 63 (48-79) in the MDS cohorts respectively. Of the 43 pts evaluable for response (21 AA, 22 MDS), there were 13 (62%) responders (4 CR, 8 PR, 1 HI) in AA cohort and 6 (27%) responders (2 CR, 4 HI) in the MDS cohort. Median age of responders was 59 (19-79). The median time to response (TTR) was 3.2 months. Of the 46 pts who received treatment, 20 pts (43%) were HLA-DR15 positive, 22 (48%) were negative, and 4 (9%) were not checked. In the MDS cohort, 9 (39%) pts were HLA-DR15 positive and none responded. In the AA cohort, 11 (48%) were HLA-DR15 positive, out of which 6 (55%) responded. Among the 19 responding pts described above, 6 (32%) were HLA-DR15 positive and all had AA. The median disease free survival for responders (CR & PR) is 26 months. The median overall survival of responders has not been reached, compared to 20 months for nonresponders (p<0.001). Overall the treatment was tolerable. The most common grade 3/4 toxicities were thrombocytopenia (43%), neutropenia (41%), transaminase elevation (13%), hyperbilirubinemia (7%), infection/fever (7%), and hyperglycemia (4%). Grade 3/4 dyspnea, abdominal pain, and hypertension occurred in 1 patient each. Twenty pts (43%) had infusion related reactions including fever, chills, and dyspnea that was manageable with supportive care. The combination of rATG, cyclosporine, steroids, and G-CSF is a well tolerated, effective regimen in the treatment of aplastic anemia and also has activity in a subset of pts with MDS. The rate of serious infections was relatively low, but infusion reactions were common and should be managed with premedication and supportive care. HLA-DR15 positivity correlated with response in patients with AA, but not in MDS. Responses were slow to occur, but durable, and associated with improved survival. Disclosures: Kadia: Genzyme: Research Funding. Ravandi:Genzyme: Honoraria.

Phase II Study of Thymoglobulin, Cyclosporine and G-CSF for Initial Treatment of Aplastic Anemia and Low Risk Myelodysplastic Syndrome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5080-5080
Author(s):  
Ravi n Jain Garg ◽  
Guillermo Garcia-Manero ◽  
Stefan Faderl ◽  
Jorge Cortes ◽  
Charles Asa Koller ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Low Risk ◽  
Significant Activity ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

Abstract Aplastic anemia (AA) is treated with equine anti-thymocyte globulin (hATG) and cyclosporine with response rates up to 65%. Rabbit anti-thymocyte globulin (rATG, Thymoglobulin®) has been used successfully in relapsed and refractory patients with AA, reducing the risk associated with readministration of equine preparations. Immunosuppressive therapy is also effective in some subsets of patients with Myelodysplastic syndrome (MDS). To evaluate if the combination of rATG, cyclosporine and G-CSF is safe and effective as first-line treatment of AA and low-risk MDS. In this single-arm, phase II study, we investigated the efficacy (primary endpoint) and safety (secondary endpoint) of combined rATG, cyclosporine and G-CSF as first-line therapy for patients with AA and Hypoplastic MDS. After 8 patients were enrolled, the study was modified to also include patients with low/intermediate-1 per the International Prognostic Scoring System. Thymoglobulin 3.5 mg/kg (or 2.5 mg/kg/day for patients ≥55 years) was given for 4 days in the first 10 patients and for 5 days in the remaining patients. Methylprednisolone (1 mg/kg/day) was given for 5 days followed by a tapering dose of oral prednisone. G-CSF (5 μg/kg) was given subcutaneously daily for up to 3 months starting after thymoglobulin. Cyclosporine (5 mg/kg) was given daily and continued for 6 months or longer at the discretion of the treating physician. All patients received prophylactic broad-spectrum antimicrobials. Responses were assessed about 3 months after initiating therapy. Thirty-six patients have been enrolled on study with 3 patients choosing alternate therapies and 1 patient dying before initiation of therapy. Among the thirty-two patients treated, 4 have been on study for less than 2 months; therefore 14 patients with AA and 14 with MDS were evaluable for a response. The median age was 62 years (20–83) for patients with AA and 63 (42–80) for patients with MDS. Thirteen of the fourteen (93%) patients with AA responded (5 CR, 7 PR, 1 HI-N), while four of 14 (29%) patients with MDS responded (1 CR, 3 PR). For patients with AA, the median time to response (TTR) was 93 days (79–623). For patients with MDS, the median TTR was 111 days (77–139). The median response duration for both groups has not been reached. Side effects were listed for 30 of 36 patients on treatment. The main grade 3/4 toxicities included thrombocytopenia in 20 patients (67%), anemia in 8 (27%), leukopenia in 17 (57%), and neutropenic fever in 4 (13%). Other grade 3/4 toxicities included renal failure, hypertension, pneumonia, urinary tract infection, fever, leukocytosis, increased liver function tests, hyperglycemia, and syncope (in 1 patient each). The combination of rabbit thymoglobulin (rATG), cyclosporine and G-CSF is safe and effective in first-line treatment of AA and has significant activity in low-risk MDS.

Cetuximab use without chronic antihistamine premedication

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13521-13521 ◽  
Author(s):  
J. Timoney ◽  
K. Y. Chung ◽  
V. Park ◽  
R. Trocola ◽  
C. Peake ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Center ◽  
First Year ◽  
Institutional Practice ◽  
Chemotherapy Administration ◽  
Time Period ◽  
Life Threatening ◽  
Anaphylactoid Reactions ◽  
Grade 3 ◽  
Severe Grade

13521 Background: Cetuximab is a human-murine chimeric monoclonal antibody against EGFR with approximately a 3% reported incidence of severe (≥ grade 3) anaphylactoid reactions. The overwhelming majority of such reactions have been reported with the initial dose of cetuximab. Diphenhydramine (Benedryl)or a related antihistamine is often given as a premedication for cetuximab, however this may cause fatigue or other side effects. Most early clinical trials of cetuximab permitted investigator discretion in use of premedication beyond the initial cetuximab dose. Methods: We obtained an IRB waiver of authorization to review the records of patients treated with cetuximab at Memorial Sloan Kettering Cancer Center for the first year of commercial availability of cetuximb (Feb, 2004 through Feb, 2005). Computerized pharmacy records were reviewed to identify all patients who were treated with cetuximab (outside of a clinical trial) and use of premedication was then evaluated. Records of institutional adverse event reports regarding chemotherapy administration were reviewed, and, any moderate or severe/life-threatening reactions were evaluated for presence or absence of concurrent premedication. Results: As per our institutional guidelines, all patients received 50 mg of diphenhydramine prior to the initial loading dose of cetuximab, and 25 mg of diphenhydramine prior to the second dose. While there was inconsistency in terms of cessation of diphenhydramine, overall a total of 115 patients received one or more doses of cetuximab without premedication. A total of 746 doses of cetuxmab without diphenhydramine premedication were given over this time period. No severe/life-threatening reactions to cetuximab occurred during these doses given without premedication. Conclusions: Omission of diphenhydramine premedication after the initial two doses of cetuximab is our current institutional practice, and appears not to alter the safety profile of cetuximab. Considering the side effects of diphenhydramine, routine long tern use of antihistamine premedication with cetuximab administration does not appear to be warranted. [Table: see text]

scholarly journals Feasibility of Nighttime Radiotherapy for Physically Independent Patients

2019 ◽  
pp. 1-3
Author(s):  
Yukihiro Hama ◽  
Yukihiro Hama
Keyword(s):  
Radiation Therapy ◽  
Retrospective Study ◽  
Side Effects ◽  
Helical Tomotherapy ◽  
Working Hours ◽  
Night Time ◽  
Life Threatening ◽  
Hospital Visits ◽  
Grade 3 ◽  
Severe Grade

Objective: Daily hospital visits for radiation therapy during working hours, five days a week, are sometimes burdensome to cancer patients who are working or studying. The purpose of this study was to evaluate the feasibility and safety of night-time radiation therapy for physically independent patients. Methods: This retrospective study consisted of 100 consecutive patients with various types of malignancies treated by helical tomotherapy at night (6:00 PM or later). The safety and feasibility of nighttime radiation therapy were evaluated. Results: Among the 100 patients, 20 (20%) developed mild (Grade 1) or moderate (Grade 2) radiationinduced side effects during the treatment. No patient developed severe (Grade 3) or life-threatening (Grade 4) adverse events during, immediately after, or three months after radiation therapy. There were no physical or mental disadvantages caused by night-time radiation therapy. Conclusion: Night-time radiation therapy is feasible and acceptable for physically independent patients.

Phase II study of thymoglobulin, cyclosporine and G-CSF for initial treatment of aplastic anemia and low risk myelodysplastic syndrome

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 7093-7093
Author(s):  
R. J. Garg ◽  
N. Shah ◽  
G. Garcia-Manero ◽  
S. Stefan Faderl ◽  
J. E. Cortes ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Phase Ii ◽  
Initial Treatment ◽  
Phase Ii Study ◽  
Low Risk

scholarly journals Dose of Deferasirox Correlates with Effects but Is Different in Low-Risk Myelodysplastic Syndrome and Aplastic Anemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3075-3075
Author(s):  
Ruoxi Zhang ◽  
Zhao Wang ◽  
Bing Han
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Exposure Time ◽  
Conflicts Of Interest ◽  
Hematological Parameters ◽  
Elevated Serum ◽  
Low Risk ◽  
Dose Effect ◽  
Minimum Dose

Abstract Backgrou n d : Patients with low-risk myelodysplastic syndrome (MDS) and aplastic anemia (AA) often need transfusions, which may accelerate the iron overload. The aim of this study was to evaluate the efficacy, safety and dose-effect relation of deferasirox (DFX) for patients with low-risk MDS and AA who were refractory to regular treatment in the real-world setting. M ethods: This was a retrospective study. Patients with low-risk MDS or AA who failed to standard treatments and were transfusion-dependent were enrolled. DFX was given as the only treatment apart from transfusion. Patients were recorded for their medical history, laboratory tests, nuclear magnetic resonance (MRI), echocardiography and calculated for their overall survival (OS). Dose-effect relations of DFX were evaluated after the first 6 months. Total annual exposure of DFX was calculated after 12 months, expressed as accumulated exposure time at dose of 20mg/kg/d. R esults: Of the 112 patients finally enrolled, 61 (54.5%) were low-risk MDS and 51 (45.5%) were AA. The median age was 56 (10, 89) years and 52.7% patients were males. The minimum dose of DFX for significant SF decrease was 20 mg/kg/d at 6 months; and the minimum accumulation of DFX had to reach 9 months at 20 mg/kg/d to maintain the efficacy at the time of 12 months for patients with low-risk MDS (p＜0.050). Different from MDS, the minimum dose for significant SF decrease was 10 mg/kg/d at 6 months; and the minimum accumulation had to reach 3 months at 20 mg/kg/d to maintain the efficacy at the time of 12 months for patients with AA (p＜0.050). Meanwhile, with same dose of exposure, significant improvements in hematological parameters were also observed in AA, but no dose-effect relations were found in MDS. 62.3% MDS and 51.0% AA patients stopped transfusion in the next 6 months. Erythroid responders had lower SF than non-responders after 12 months of DFX, both for MDS and AA (p＜0.05). Lower alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with baseline after 12 months of DFX were observed and longer exposure time correlated with lower ALT (p＜0.050). No significant changes in cardiac function, however. Similar side effects were found in MDS and AA, with gastrointestinal disorders and elevated serum creatinine the most common. Higher dose and longer exposure time of DFX correlated with longer overall survival, both for patients with MDS and AA (p＜0.050). Conclusion: Although dose of DFX varies greatly in different individuals, a significant decrease in SF and an improvement of hematologic parameters, organ functions, or even overall survival can be achieved if the accumulate dose reaches a certain level. In that case, patients with low-risk MDS need higher dose than those with AA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy and Safety of Eltrombopag Combined with Cyclosporine As First-Line Therapy in Adults with Severe Acquired Aplastic Anemia: Results of the Interventional Phase 2 Single-Arm Soar Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2174-2174
Author(s):  
Carlos Vallejo ◽  
Jun Ho Jang ◽  
Carlo Finelli ◽  
Efreen Montaño Figueroa ◽  
Lalita Norasetthada ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Research Funding ◽  
Efficacy And Safety ◽  
First Line ◽  
Advisory Committees ◽  
Transfusion Independence ◽  
First Line Therapy ◽  
Insufficient Response ◽  
Grade 3

Abstract Background: Severe aplastic anemia (SAA) is a rare bone marrow failure disorder associated with significant morbidity and mortality. SAA is characterized by severe pancytopenia and a hypocellular (&lt;25%) bone marrow. The standard of care treatment is hemopoietic stem cell transplant or immunosuppressive therapy (IST) for patients (pts) who are ineligible for transplant. IST usually comprises an antithymocyte globulin (ATG) derived from horse or rabbit, and cyclosporine A (CsA). Although IST can be an effective treatment, individual intolerance, insufficient response, relapse, and clonal evolution remain significant limitations. The lack of global availability of the more effective horse ATG also leaves many pts with limited treatment options and poorer outcomes. In addition, pts with SAA often require transfusions which can be burdensome and negatively impact their quality of life. Eltrombopag (ETB) is indicated for use in pts with SAA who have had an insufficient response to IST (FDA PI, 2014) or are refractory to IST (EMA SmPC, 2015). More recently in the USA, ETB may also be used in combination with IST as first-line (1L) treatment (FDA PI, 2018). Aims: To assess the efficacy and safety of ETB + CsA (without ATG) as 1L therapy in adult pts with SAA. Methods: SOAR (NCT02998645) is a Phase 2, single-arm, multicenter, open-label study. Treatment-naive pts with SAA received ETB + CsA for 6 months; responders continued CsA therapy for an additional 24 months (later reduced to 18 months). The primary efficacy endpoint was overall response rate (ORR) by 6 months. ORR was defined as the proportion of pts with complete response ([CR] = absolute neutrophil count [ANC] ≥1000/μL AND platelet count ≥100,000/μL AND hemoglobin ≥10 g/dL) plus the proportion of pts with partial response ([PR] = any 2 of the following counts: ANC ≥500/μL; platelet count ≥20,000/μL; automated reticulocyte count ≥60,000/μL, but not sufficient for a CR). CR and PR were confirmed by 2 assessments ≥7 days apart; transfusion restrictions were also applied. For the primary endpoint to be considered 'clinically meaningful' at least 17/54 pts treated were required to have a response. Other endpoints included ORR by 3 months, ORR at 6 months (ie, confirmed response at the 6-month visit), and transfusion independence, which was defined as transfusion not being required in a period of ≥28 days for platelet transfusions and ≥56 days for red blood cell (RBC) transfusions. Results: Pts (N=54) had a median (interquartile range [IQR]) age of 55.0 (40.0-67.0) years and 63.0% were male. The majority of pts were White (40.7%) or Asian (40.7%). The median (IQR) duration of exposure to ETB and CsA was 5.7 (2.5-5.8) months and 5.7 (2.4-8.1) months, respectively, and the median (IQR) daily ETB dose was 150.0 (100.0-150.0) mg/day. In the full analysis set, the primary endpoint was met, with 25/54 pts having a CR or PR by 6 months (ORR 46.3%; 95% confidence interval [CI], 32.6-60.4%). Of the 25 responders, 2 (3.7%) achieved a CR by 6 months. ORR by 3 months was 40.7% (95% CI, 27.6-55.0%; n=22/54), and ORR at 6 months was 37.0% (95% CI, 24.3-51.3%; n=20/54). 70.4% of all pts qualified for ≥1 period of RBC and/or platelet transfusion independence by 6 months, including all 25 (100%) responders and 13/29 (44.8%) non-responders (Fig. 1). 40.7% of all pts (responders: 68.0%; non-responders: 17.2%) qualified for ≥1 period of RBC transfusion independence (corresponding percentages for platelet transfusion independence were the same as for the combined RBC and/or platelet endpoint). Adverse events (AEs) occurred in 52/54 (96.3%) pts; 45 (83.3%) pts experienced treatment-related AEs (TAEs), 23 (42.6%) of whom had a grade ≥3 TAE. The most common all-grade AEs were increased blood bilirubin (40.7%), nausea (29.6%), increased alanine aminotransferase (22.2%), and diarrhea (22.2%). Seven (13.0%) pts discontinued treatment due to grade ≥3 AEs. There were 8 on-treatment deaths (aplastic anemia [n=3]; COVID-19, hemorrhage, multi-organ dysfunction syndrome, pyrexia, and thrombosis [all n=1]); no deaths were considered treatment-related. Conclusion: Data from the SOAR study indicate that ETB + CsA may be beneficial for pts with SAA ineligible for transplant who cannot access or tolerate ATG. All responders and almost half of non-responders qualified for ≥1 period of transfusion independence by 6 months, suggestive of a decreased transfusion burden. No new safety signals were identified. Figure 1 Figure 1. Disclosures Vallejo: Novartis: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Finelli: Takeda: Consultancy; Celgene BMS: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Calado: Agios: Membership on an entity's Board of Directors or advisory committees; AA&MDS International Foundation: Research Funding; Alexion Brasil: Consultancy; Instituto Butantan: Consultancy; Novartis Brasil: Honoraria; Team Telomere, Inc.: Membership on an entity's Board of Directors or advisory committees. Peffault De Latour: Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Apellis Pharmaceuticals Inc: Consultancy, Honoraria; Swedish Orphan Biovitrum AB: Consultancy, Honoraria. Kriemler-Krahn: Novartis: Current Employment. Haenig: Novartis: Current Employment. Maier: Novartis: Current Employment. Scheinberg: Alexion pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; BioCryst Pharmaceuticals: Consultancy; Roche: Consultancy; Abbvie: Consultancy. OffLabel Disclosure: In the United States, eltrombopag is a thrombopoietin receptor agonist indicated in combination with standard immunosuppressive therapy (ATG + CsA) for the first-line treatment of adult and pediatric patients aged 2 years and older with severe aplastic anemia (SAA). It is also indicated for the treatment of patients with SAA who have had an insufficient response to immunosuppressive therapy. The SOAR trial aims to assess the efficacy and safety of eltrombopag + CsA (without ATG) as first-line therapy in adult patients with SAA.

A Critical Overview of Systematic Reviews of Chemotherapy for Advanced and Locally Advanced Pancreatic Cancer using both AMSTAR2 and ROBIS as Quality Assessment Tools

2020 ◽  
Vol 15 ◽  
Author(s):  
Amit Dang ◽  
Surendar Chidirala ◽  
Prashanth Veeranki ◽  
BN Vallish
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Systematic Reviews ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Risk Of Bias ◽  
Low Risk ◽  
Locally Advanced Pancreatic Cancer ◽  
Grade 3 ◽  
Critical Overview

Background: We performed a critical overview of published systematic reviews (SRs) of chemotherapy for advanced and locally advanced pancreatic cancer, and evaluated their quality using AMSTAR2 and ROBIS tools. Materials and Methods: PubMed and Cochrane Central Library were searched for SRs on 13th June 2020. SRs with metaanalysis which included only randomized controlled trials and that had assessed chemotherapy as one of the treatment arms were included. The outcome measures, which were looked into, were progression-free survival (PFS), overall survival (OS), and adverse events (AEs) of grade 3 or above. Two reviewers independently assessed all the SRs with both ROBIS and AMSTAR2. Results: Out of the 1,879 identified records, 26 SRs were included for the overview. Most SRs had concluded that gemcitabine-based combination regimes, prolonged OS and PFS, but increased the incidence of grade 3-4 toxicities, when compared to gemcitabine monotherapy, but survival benefits were not consistent when gemcitabine was combined with molecular targeted agents. As per ROBIS, 24/26 SRs had high risk of bias, with only 1/26 SR having low risk of bias. As per AMSTAR2, 25/26 SRs had critically low, and 1/26 SR had low, confidence in the results. The study which scored ‘low’ risk of bias in ROBIS scored ‘low confidence in results’ in AMSTAR2. The inter-rater reliability for scoring the overall confidence in the SRs with AMSTAR2 and the overall domain in ROBIS was substantial; ROBIS: kappa=0.785, SEM=0.207, p<0.001; AMSTAR2: kappa=0.649, SEM=0.323, p<0.001. Conclusion: Gemcitabine-based combination regimens can prolong OS and PFS but also worsen AEs when compared to gemcitabine monotherapy. The included SRs have an overall low methodological quality and high risk of bias as per AMSTAR2 and ROBIS respectively.

Cutaneous Adverse Events of Immune Checkpoint Inhibitors: A Summarized Overview

2019 ◽  
Vol 14 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Kerasia-Maria Plachouri ◽  
Eleftheria Vryzaki ◽  
Sophia Georgiou
Keyword(s):  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Maculopapular Rash ◽  
Symptomatic Treatment ◽  
Stevens Johnson Syndrome ◽  
Life Threatening ◽  
Skin Side Effects

Background:The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.Objective:To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.Method:English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.Results:The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.Conclusion:Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.

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