Myositis and myasteniform syndrome related to pembrolizumab

2021 ◽  
Vol 14 (7) ◽  
pp. e241766
Author(s):  
Pablo Sanchez-Sancho ◽  
Albert Selva-O'Callaghan ◽  
Ernesto Trallero-Araguás ◽  
Javier Ros ◽  
Bruno Montoro
Keyword(s):  
Clinical Trial ◽  
Case Report ◽  
Adverse Events ◽  
Treatment Approach ◽  
Specific Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Muscular Weakness ◽  
Glucocorticoid Treatment ◽  
Immune Mediated

This case report concerns a 63-year-old man affected by metastatic undifferentiated liposarcoma. After receiving pembrolizumab as a second-line treatment in a clinical trial, the patient experienced an immune-mediated myocarditis, myositis and myasteniform syndrome. The last two adverse events showed significant clinical relevance in terms of severity, duration and the required specific treatment.Initial treatment approach consisted in pulses of 1 g of methylprednisolone, followed by 2 mg/kg/day, with clinical improvement. After 12 days, the immune-mediated myasteniform syndrome worsened, with dysphagia, dysphonia, bilateral palpebral ptosis and respiratory difficulty. Due to the refractoriness to glucocorticoid treatment, it was decided to initiate intravenous immunoglobulin at 2 g/kg, followed by 2 mg/kg every 4 weeks once discharged and mycophenolate 500 mg/12 hours, in order to reduce the dose of glucocorticoids.After 2 months, the patient presented an optimal clinical evolution, without muscular weakness and referred to an improvement in dysphagia and speech.

Immunotherapy toxicity in patients over 65 years.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12027-12027
Author(s):  
Miriam Mendez ◽  
Blanca Cantos ◽  
Beatriz Nuñez García ◽  
Juan Cristobal Sanchez ◽  
Fernando Franco ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Older Patients ◽  
Hemophagocytic Syndrome ◽  
Routine Clinical Practice ◽  
Second Line ◽  
Risk Of Death ◽  
Immune Mediated ◽  
Radiological Data ◽  
Digestive Toxicity

12027 Background: Cancer patients increasingly present an advanced age at diagnosis; 50% of the new cases are over 65 years old, being underrepresented in clinical trials. The safety of immunotherapy has not been adequately evaluated in the subgroup of elderly patient. In this population, with more comorbidities, adverse events may be less well tolerated and have more serious consequences. Methods: A retrospective observational study was developed, including all patients treated with immunotherapy at our center between January 2015 to February 2020. Of the total (279 patients), the analysis was performed with the 105 patients ≥65 years of age who had received at least one cycle (in routine clinical practice or within an unblinded clinical trial). All clinical and radiological data of the patients were collected. Results: From the total, the majority had a lung carcinoma or melanoma, treated with nivolumab or pembrolizumab either in first or second line. 63% had died at the time of the analysis. The frequency of toxicities: digestive (15%), pneumonitis (12%) and endocrine (9%). We divided the population into 65-75 years (76 patients) or > 75 years (29 patients), analyzing the frequency of toxicity and deaths secondary to it. Those > 75 years had more digestive toxicity (25% vs 11%), but less pneumonitis (3% vs 15%). There were 7 deaths (6%) related to treatment: 2 patients with ipilimumab-nivolumab (28%), 2 nivolumab (28%), 2 pembrolizumab (28%), and 1 ipilimumab (16%). 5 patients were > 75 years old (median 78 years) presenting a higher mortality rate in relation to toxicity (4% vs 20%, p 0.02) and a worse median survival (29 vs 23 months). The fatal toxicities were: 3 neurological (2 meningoencephalitis and 1 acute diffuse axonal denervation), 2 hepatic, 1 hemophagocytic syndrome and 1 myocarditis. Conclusions: The most frequent toxicity was digestive, but those that led to death were neurological, hepatic, hematological and cardiac. In our series, neurological and cardiac adverse events accounted for 57% of immunotherapy deaths in older patients. Our data warn that patients over 75 years have a higher risk of death from immune-mediated events. In addition, these would be mainly neurological and cardiac, which represents a diagnostic and treatment challenge for oncologists.[Table: see text]

scholarly journals P44-4 A case report of four patients received ramucirumab monotherapy as second-line treatment for advanced gastric cancer

2021 ◽  
Vol 32 ◽  
pp. S353
Author(s):  
Kei Onodera ◽  
Akiko Ichiyanagi ◽  
Akari Ueno ◽  
Motohiro Tani ◽  
Shuji Sato ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Case Report ◽  
Advanced Gastric Cancer ◽  
Line Treatment ◽  
Second Line

scholarly journals Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kensuke Nakamura ◽  
◽  
Aiki Marushima ◽  
Yuji Takahashi ◽  
Akio Kimura ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Adverse Events ◽  
Controlled Trial ◽  
Insurance Coverage ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Consciousness Disturbance ◽  
Multicenter Randomized Controlled Trial ◽  
Severe Adverse Events

Abstract Background Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE. Methods This multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is “continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance.” In both groups, diazepam is initially administered at 1–20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000–3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes. Discussion The present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application. Trial registration Japan Registry of Clinical Trials jRCTs031190160. Registered on December 13, 2019

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

Nivolumab and ipilimumab for second-line therapy in elderly patients with advanced esophageal squamous cell cancer: Safety interim analysis of the RAMONA trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4029-4029
Author(s):  
Nicolai Hartel ◽  
Nadja M Meindl-Beinker ◽  
Martin Maenz ◽  
Wolfgang Hiegl ◽  
Johannes Betge ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Interim Analysis ◽  
Treatment Duration ◽  
Safety Assessment ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

4029 Background: Advanced esophageal squamous cell cancer (ESCC) is frequently diagnosed in elderly patients (pts) with additional comorbidities. Limited treatment options are available. We report the safety interim analysis of a phase II clinical trial evaluating nivolumab and ipilimumab as second-line therapy for advanced ESCC in elderly pts. Methods: RAMONA is a multicenter open-label phase II trial assessing nivolumab/ipilimumab combination therapy in elderly pts (≥65 years). The geriatric status of the pts was assessed using the G8 screening tool and the Deficit Accumulation Frailty Index (DAFI). After a run-in phase of 3 cycles nivolumab (240mg Q2W), cohort assignment was based on a safety assessment. Pts with toxicities grade ≤2 were considered eligible for escalation to nivolumab (240mg Q2W)/ipilimumab (1mg/kg Q6W) combination therapy (cohort B). Other pts remained on nivolumab monotherapy (cohort A). Primary endpoint is overall survival (OS). Key secondary endpoint is time to Quality of Life deterioration defined as a loss of ≥ 10 points in the EORTC QLQ-C30 compared to baseline. Adverse events were assessed according to NCI-CTCAE version 4.03. Results: From February 2018 until February 2020, 69 pts entered the study. 61 pts were eligible for safety interim analysis. Median age of the pts was 71.9 yrs (± 5.4), median KPS score was 80% (50-100%). In 73.8% of the pts, metastases were detected at the time of study inclusion. Most pts received the IO therapy in ≥ 2nd line (91.8%). The mean G8-score at screening was 11.9 points (46 pts ≤ 14 points, 75.4%) (mean DAFI: 0.19). Based on safety assessment, 42 pts were escalated to nivolumab/ipilimumab, while 9 pts remained on nivolumab monotherapy. 10 pts were not allocated at the time of analysis. Median numbers of cumulative doses were 3.0 [1.0 - 3.0] for the run-in phase (nivolumab), 6.0 [1.0 – 48.0] for nivolumab therapy (cohort A/B) and 2.5 [1.0 – 16.0] for ipilimumab (cohort B). Median treatment duration was 144.5 days (56-781 days) in cohort A and 231 days (85-484 days) in cohort B. Frailty indices remained stable after 3 cycles of nivolumab with limited toxicity at the time of the safety assessment. Drug-related treatment emergent adverse events (AEs) were observed in 42 pts (68.9%); 29/42 in cohort A, 8/9 in cohort B, and 5/10 pts not allocated at the time of analysis. Grade ≥3 AEs were detected in 9 pts of 42 in cohort A and 4 of 9 pts in cohort B. Drug-related treatment emergent serious adverse events (SAEs) were detected in 12 pts (19.7%); 8/42 in cohort A, 2/9 pts in cohort B, and 2/10 pts not yet allocated. Conclusions: Combined nivolumab/ipilimumab is a safe and feasible second-line therapy for elderly pts with advanced ESCC. Most pts could be escalated to nivolumab/ipilimumab. Treatment duration was exceptional long for a subset of pts. Clinical trial information: NCT03416244.

Second Line Treatment? Utility of Lithium´s Use in Bipolar Mixed States. a Clinical Case Report.

2015 ◽  
Vol 30 ◽  
pp. 1165
Author(s):  
H. Esteves ◽  
G. Pereira ◽  
Z. Gameiro ◽  
A. Aleixo ◽  
M. Bairrão
Keyword(s):  
Case Report ◽  
Clinical Case ◽  
Line Treatment ◽  
Second Line ◽  
Mixed States ◽  
Treatment Utility

Stent-over-sponge (SOS): a novel technique complementing endosponge therapy for foregut leaks and perforations

Endoscopy ◽  
2017 ◽  
Vol 50 (02) ◽  
pp. 148-153 ◽  
Author(s):  
Piero Valli ◽  
Joachim Mertens ◽  
Arne Kröger ◽  
Christoph Gubler ◽  
Christian Gutschow ◽  
...  
Keyword(s):  
Adverse Events ◽  
Success Rate ◽  
Vacuum Therapy ◽  
Line Treatment ◽  
Second Line ◽  
Metal Stent ◽  
First Line ◽  
Novel Technique ◽  
Upper Gastrointestinal ◽  
First Line Treatment

Abstract Background and study aims Endoluminal vacuum therapy (EVT) has evolved as a promising option for endoscopic treatment of foregut wall injuries in addition to the classic closure techniques using clips or stents. To improve vacuum force and maintain esophageal passage, we combined endosponge treatment with a partially covered self-expandable metal stent (stent-over-sponge; SOS). Patients and methods Twelve patients with infected upper gastrointestinal wall defects were treated with the SOS technique. Results Indications for SOS were anastomotic leakage after surgery (n = 11) and chronic foregut fistula (n = 1). SOS treatment was used as a first-line treatment in seven patients with a success rate of 71.4 % (5/7) and as a second-line treatment after failed previous EVT treatment in five patients (success rate 80 %; 4/5). Overall, SOS treatment was successful in 75 % of patients (9/12). No severe adverse events occurred. Conclusion SOS is an effective method to treat severely infected foregut wall defects in patients where EVT has failed, and also as a first-line treatment. Comparative prospective studies are needed to confirm our preliminary results.

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

Economic evaluation of crizotinib, alectinib, ceritinib, and brigatininb in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) as second-line treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21104-e21104
Author(s):  
Nimer S. Alkhatib ◽  
Briana Choi ◽  
Hala Halawah ◽  
Matthias Calamia ◽  
Dexter Gulick ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Incremental Cost ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Reference Drug ◽  
First Line Therapy ◽  
Line Therapy ◽  
Life Years

e21104 Background: Crizotinib, alectinib, ceritinib, and brigatinib are approved as second line treatment for ALK+ NSCLC. Crizotinib was the first ALK inhibitor for first line therapy approved by Food and Drug Administration (2011) then ceritinib (2014), alectinib (2015), and brigatinib (2017) were approved as second line drugs. Following more data, these agents were approved as the first line therapy (2017 for ceritinib and alectinib; 2020 for brigatinib). These remain as a treatment option in patients who fail the first line therapy. Cost-effectiveness/utility analyses were conducted to assess clinical efficacy with varying costs of the agents. Methods: A three state Markov model were assumed (progression free, progression and death). Progression free survival (PFS) curves were digitized and fitted with exponential function. US payer perspective, a lifetime horizon, and discount rate of 3% were applied. Drug costs were Redbook wholesale acquisition cost. Other costs included were monitoring, adverse events and disease progression from published data (US$ 2020). Adverse events reported >5% in patients were included. Measured outcomes were PFS life years (PFSLY) and quality adjusted life years (PFSQALY). Crizotinib was the reference drug. Incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) and lost were estimated. Base case (BCA) and probabilistic sensitivity analyses (PSA) were conducted. Results: Crizotinib was the reference drug for the following outcomes. For alectinib, with the decremental cost of -$14,653 (-$14,712), the incremental PFSLY of 0.16 (0.16) and PFSQALY of 0.05 (0.05) resulted in an ICER / PFSLYG of -$89,337 (-$88,604) and an ICUR / PFSQALYG of -$269,835 (-$266,510). For brigatinib, with the decremental cost of -$14,975 (-$14,954), the incremental PFSLY of 0.01 (0.01) and PFSQALY of ̃0.01 (0.02) yielded an ICER / PFSLYG of -$1,982,962 (-$1,431,631) and an ICUR / PFSQALYG of -$2,140,534 (-$570,538). For ceritinib, with the incremental cost of $7,590 ($7,514), there were decremental PFSLY of -0.01 (-0.01) and PFSQALY of -0.03 (-0.03). Conclusions: As second line treatment, crizotinib, ceritinib, and brigatinib had comparable PFSLYs and PFSQALYs while alectinib had the most PFSLY and PFSQALY and the lowest cost. Therefore, alectinib is the most cost-effective treatment for treating ALK+ NSCLC as the second line therapy.[Table: see text]

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