Discontinuation Due to Toxicity Limits Treatment Duration of BTK Inhibitors in Non-Hodgkin Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4685-4685
Author(s):  
Drew G Gerber ◽  
Yichun Cao ◽  
Jeffrey M. Switchenko ◽  
Kelly Valla ◽  
Jonathon B. Cohen
Keyword(s):  
Adverse Effects ◽  
Disease Progression ◽  
Median Duration ◽  
Gastrointestinal Toxicity ◽  
Categorical Variables ◽  
Duration Of Treatment ◽  
Significant Difference ◽  
Voluntary Choice ◽  
Btk Inhibitors ◽  
Novel Agent

Abstract Background: Although clinical trial data exist describing the adverse effects of Bruton's tyrosine kinase inhibitors (BTKi)s, the patient experience outside clinical trials, including differences among agents is less well-described. We evaluated the selection criteria, efficacy and toxicities related to the use of BTKi at our site. Methods: A retrospective patient chart review was used to collect data from patients treated with one or more BTKi. Demographics, prior therapies, duration of treatment, response to treatment, and incidence and severity of pre-determined toxicities of interest were collected for each patient. Descriptive statistics for each variable were reported. Association between variables of interest and the study cohort were examined using ANOVA for categorical variables and Pearson correlation coefficient for continuous variables. Survival and duration of treatment were estimated using the Kaplan-Meier method according to first novel agent. Survival analysis for each novel agent was conducted using Cox proportional hazards models and log-rank tests. Results: One hundred forty patients were included in this study, including 94 patients with CLL, 24 with MCL, and 22 with other NHL subtypes. One hundred thirteen patients received ibrutinib, while 17 patients received acalabrutinib (n=16) or zanubrutinib (n=1), which were combined in the statistical analysis. Of patients receiving ibrutinib, 69% reported at least one toxicity event during the duration of their treatment. Across all patients who received ibrutinib, 35 individuals did not report a toxicity, 48 individuals reported one toxicity, and 30 individuals reported two or more toxicities. Among the 78 patients who experienced at least one toxicity, 41 (52.5%) discontinued the medication due to these adverse effects, most commonly cytopenias (n=9), diarrhea (n=8), and fatigue (n=9). 57% of patients who reported diarrhea, 36% of patients who reported cytopenias, and 33% of patients who reported fatigue discontinued therapy due to that reported AE. In total, 60/113 patients receiving ibrutinib discontinued therapy, including 40 (66%) due to toxicity and 14 (23.3%) due to disease progression. The remaining patients discontinued therapy due to voluntary choice of new therapy or due to personal decision to stop treatment. Patients remained on ibrutinib therapy for a median duration of 40 months. 53% of patients taking zanabrutinib or acalabrutinib reported at least 1 toxicity, but only 11.7% of patients discontinued therapy for any reason. All patients who discontinued zanubrutinib/acalabrutinib therapy did so due to toxicity, with no patients ceasing therapy due to disease progression. Because only 2 of 17 patients discontinued zanubrutinib/acalabrutinib treatment, a raw median duration of treatment was calculated to be 5 months. 12.4% of patients taking ibrutinib experienced a gastrointestinal toxicity, whereas 5.9% of patients taking acalabrutinib/zanubrutinib experienced a gastrointestinal toxicity (Table 1). Additionally, 8% of individuals taking ibrutinib reported a musculoskeletal toxicity, while no acalabrutinib/zanubrutinib patients reported a musculoskeletal toxicity. There were no statistically significant differences in frequency of toxicities encountered, possibly due to study size. Other toxicities common to all analyzed BTK inhibitors included hematological, cardiovascular, and constitutional adverse effects with no significant difference between agents. Conclusions: We identified that >1/3 of individuals taking BTK inhibitors are stopping therapy prematurely due to toxicity related outcomes rather than due to disease progression. Our findings suggest that proactive identification and management of adverse effects could prolong therapy duration and provide better outcomes for patients. Strategies to personalize therapy selection to limit therapy discontinuation due to toxicity are needed as additional targeted agents are developed. Figure 1 Figure 1. Disclosures Valla: BeiGene: Speakers Bureau. Cohen: Janssen, Adaptive, Aptitude Health, BeiGene, Cellectar, Adicet, Loxo/Lilly, AStra ZenecaKite/Gilead: Consultancy; Genentech, Takeda, BMS/Celgene, BioInvent, LAM, Astra Zeneca, Novartis, Loxo/Lilly: Research Funding.

Efficacy and safety of anti-VEGF therapy in metastatic unresectable hepatocellular carcinoma: A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15632-e15632
Author(s):  
Lakshmi Manogna Chintalacheruvu ◽  
Avanija Buddam ◽  
Arun Kanmanthareddy ◽  
Apar Kishor Ganti
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Effects ◽  
Disease Progression ◽  
Meta Analysis ◽  
Categorical Variables ◽  
Vegf Receptor ◽  
Efficacy And Safety ◽  
Unresectable Hepatocellular Carcinoma ◽  
Significant Difference

e15632 Background:Conventional chemotherapy has limited role in metastatic unresectable hepatocellular carcinoma (HCC). Sorafenib is currently approved for metastatic unresectable HCC. We wanted to assess the efficacy and safety of other tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor (VEGF) receptor such as brivanib, linifanib and regorafenib in metastatic HCC. Methods: We have searched electronic databases Pubmed, Google scholar to identify published trials using brivanib, linifanib and regorafenib in HCC. The outcomes evaluated were overall survival, time to disease progression (TTDP) and adverse effects. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were then computed using the appropriate model for categorical variables. We used STATA 13.0 and Comprehensive Meta Analysis 2.0 software for all analyses. Results: We included seven randomized control studies. A combined analysis of these seven randomised control trials showed improved overall survival (OS) in VEGF-TKI group when compared to placebo HR - 0.79; (95% CI 0.62-1.00). However, there was no significant survival benefit of the newer VEGF receptor inhibitors when compared to sorafenib (HR - 1.05; 95% CI 0.95-1.17). The time to disease progression (TTDP) was significantly better in VEGF-TKI group as compared to placebo (HR - 0.61; 95% CI 0.39-0.97). However, there was no significant difference in TTDP between VEGF-TKI group and Sorafenib (HR - 0.88; 95% CI 0.66-1.16). Adverse effects were noted to be higher in VEGF-TKI group when compared to placebo (HR- 1.07; 95% CI 1.01-1.13). Conclusions: Treatment with TKI targeting VEGF receptor is associated with a significant improvement in OS and TTDP with tolerable side effect profile. Inhibiting the VEGF receptor pathway could lead to improved outcomes in HCC.

scholarly journals Favorable Long-Term Outcomes after Daratumumab Discontinuation in AL Amyloidosis Patients Achieving Deep Responses

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1884-1884 ◽  
Author(s):  
Alfred Chung ◽  
Gregory P. Kaufman ◽  
Surbhi Sidana ◽  
David Iberri ◽  
Erik Eckhert ◽  
...  
Keyword(s):  
Disease Progression ◽  
Board Of Directors ◽  
Median Duration ◽  
Research Funding ◽  
Control Group ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Free Interval ◽  
Significant Difference

Daratumumab (DARA) is a CD38-targeted antibody FDA-approved for the treatment of multiple myeloma (MM) and its efficacy has recently been demonstrated in the treatment of AL amyloidosis. DARA is conventionally given indefinitely until evidence of disease progression or intolerance for the treatment of MM. In AL amyloidosis, the optimal duration of therapy is not known, and patients may be treated indefinitely on maintenance, extrapolating from MM data. However, the plasma cell burden observed in AL amyloidosis is often lower than in MM, and thus certain patients achieving deep responses may have durable responses with time-limited treatment. Outcomes for patients who are observed after DARA discontinuation are not known. We report the outcomes of patients at our institution who received time-limited DARA. A retrospective analysis of AL amyloidosis patients treated at Stanford University from 2016 to 2019 with DARA monotherapy and dexamethasone for at least 2 months was performed, and patients who subsequently had DARA discontinued for reasons other than disease progression or lack of response were selected for the study. Hematologic responses were assessed by consensus guidelines. Duration on and off therapy were explored, along with time-to-next treatment or death (TTNT), defined as the time from DARA initiation to restarting/switching therapy or death. An exploratory analysis comparing TTNT between the study population and a control cohort who achieved hematologic CR and were maintained on DARA was conducted with the Kaplan-Meier method and log-rank testing. 67 patients received at least 2 months of DARA monotherapy and dexamethasone; among these, 15 patients discontinued therapy for reasons other than disease progression and were included. Median age was 66 years old and median lines of prior therapies was 4 (range: 1 - 6). Baseline difference between involved and uninvolved free light chains (dFLC) prior to DARA initiation was 2.6 mg/dL (range: 0 - 16.8 mg/dL). 10 of 15 patients had cardiac involvement with median NT-proBNP of 1982 pg/mL and 9 of 15 patients had renal involvement with median 24-hour proteinuria of 6.2 g and eGFR of 32 mL/min/1.73m2 at DARA initiation. Median duration from starting to stopping DARA was 7.8 months (range: 2 - 21 months). Median duration from achieving best hematologic response to stopping DARA was 3 months (range: 0 - 17 months). Reasons for discontinuation included: patient preference (5), fatigue/body aches (4), infection (2), other active medical comorbidities (3), and lack of perceived further benefit (1). At DARA discontinuation, median dFLC was 0.1 mg/dL (range: 0 - 2.2 mg/dL) and there were 12 hematologic CR, 1 VGPR, 1 PR, and 1 not assessable for response. Outcomes for all 15 patients are shown in Figure 1. The median treatment-free interval was 17.5 months (range: 5 - 34 months); estimated 2-year TTNT-free survival was 83% (95% CI: 61 - 100%). All 14 evaluable patients eventually achieved CR. 3 patients restarted DARA for rising dFLC, and all 3 patients demonstrated response to retreatment (2 achieving CR and 1 near PR with ongoing follow-up). There were 2 deaths. One patient with severe baseline cardiac amyloidosis developed sudden rise in dFLC after treatment-free interval of 21 months; although he rapidly achieved hematologic CR on retreatment, he died of heart failure within 2 months of restarting DARA. The other patient developed therapy-related AML while off therapy and underwent allogenic stem cell transplant but died of leukemia (censored for AL amyloidosis outcomes at transplant). There was no significant difference in the TTNT between the study group and a control group of 16 patients who achieved CR and were on continuous maintenance (Figure 2; p=0.807). AL amyloidosis patients achieving deep responses with DARA can have favorable outcomes after treatment discontinuation, including a long treatment-free interval. Although our sample size is small, the outcomes of these patients appeared comparable to those achieving CR on continuous DARA maintenance, and patients were able to regain responses when retreatment was necessary. These results suggest that DARA may be safely discontinued in patents achieving deep hematologic responses, which has significant implications for quality of life and financial burden of treatment. Future studies evaluating time-limited versus continuous DARA maintenance after achievement of deep responses are warranted. Disclosures Kaufman: Janssen: Other: travel/lodging, Research Funding. Liedtke:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; IQVIA/Jazz: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celator: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Agios: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Daratumumab for treatment of AL amyloidosis

scholarly journals Report: The effects of topical pleurotus tuberregium (PT) aqueous extract on intraocular pressure in monkeys

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256422
Author(s):  
Ghalib A. Akinlabi ◽  
Paul L. Kaufman ◽  
Julie A. Kiland
Keyword(s):  
Adverse Effects ◽  
Aqueous Extract ◽  
Species Differences ◽  
Duration Of Treatment ◽  
Significant Difference ◽  
Ocular Pressure ◽  
The Right ◽  
Feline Model ◽  
Ketamine Hcl ◽  
Pleurotus Tuberregium

Purpose In earlier experiments in Nigeria, aqueous extract of Pleurotus tuber-regium (PT) had been shown to lower intra ocular pressure (IOP) in a feline model. The aim of the current study was to determine whether PT had the same or a similar IOP-lowering effect in ocularly normal non-human primates. Methods Four monkeys were treated twice daily for 4 days with 2 x 20 μl drops of 50 mg/ml PT (pH = 4.3). The monkeys were sedated with 5–10 mg/kg ketamine HCl IM. PT was administered to the right eye and BSS to the left eye. Baseline IOP was measured just prior to beginning treatment, and on day 5 before treatment and then hourly for 3 hours, beginning 1 hour after treatment. SLEs were performed at baseline and on day 5 pre- and 3 hours post-treatment. Results There was no significant difference between IOP in treated vs control eyes in the protocol. There were no adverse effects or toxicity as seen by SLE. Conclusions The inability of the extract to lower IOP in monkeys, in contrast to ocular hypertensive cats in an earlier study, could be due to species differences or duration of treatment. Since no adverse effects were observed in the monkeys, further studies with varying durations and dosages are recommended.

Immunomodulation of pembrolizumab (pembro) treated metastatic melanoma patients (pts) after progression with sequential temozolomide (TMZ): A case series.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 123-123
Author(s):  
Umang Swami ◽  
Varun Monga ◽  
Yousef Zakharia ◽  
Mohammed M. Milhem
Keyword(s):  
T Cells ◽  
Metastatic Melanoma ◽  
Disease Progression ◽  
Median Duration ◽  
Objective Response ◽  
Case Series ◽  
Complete Response ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Duration Of Treatment

123 Background: Regulatory T cells are increased in melanoma pts and are postulated to impair objective response to immune therapies. Pembro blocks programmed death receptor-1, reverses T-cell suppression and induces antitumor activity. Continuous low dose TMZ has immunomodulatory effects resulting in selective CD4+ lymphopenia of which the T-reg population of CD4+/CD25+ T cells could be decreased significantly. TMZ has demonstrated dramatic responses after IL-2 in metastatic melanoma pts. We evaluated responses with sequential TMZ after progression on pembro in pts with metastatic melanoma. Methods: Medical records of pts with metastatic melanoma treated with pembro and TMZ at Holden Comprehensive Cancer Center between 1/1/2011 and 8/31/2016 were reviewed. Recorded data included BRAF mutation status, treatment doses, serological markers, duration of treatment and treatment related responses (immune RECIST and RECIST 1.1). Results: Overall 10 pts (7 males, 3 females) with metastatic melanoma received sequential pembro followed by TMZ after disease progression or unacceptable toxicity. Eight were BRAF negative and 7 were pretreated with ipilimumab. Median age at time of initiating pembro (2 mg/kg every 3 weeks) was 64 years (range 33-75). Pts received a median of 4 doses (2-19). Median duration of treatment was 88 days (41-464) with stable disease in 3, progressive disease (PD) in 6 and 1 not evaluable for response. All pts thereafter received TMZ (75 mg/m2 daily for 6 weeks on 8 week cycle except 1 who received 200 mg/m2 for 5 days every 4 weeks) after a median of 21.5 days (12-34) from last pembro dose. Median duration on treatment with TMZ was 75 days (20-198) resulting in 1 complete response, 1 partial response, 6 PD and 2 not evaluable for response. Pts with response to TMZ had a higher median baseline lymphocyte count at the time of initiation of pembro (4131 vs. 1715 k/uL, p < 0.05) as well as TMZ (2335 vs. 965 k/uL, p = 0.08) as compared to pts without a response. Conclusions: TMZ is an interesting alternative for metastatic melanoma pts with disease progression on pembro. Our results show a 25% response rate. Further studies in this setting are warranted.

scholarly journals The impact of demographic and clinical characteristics on diabetic painful neuropathy

2020 ◽  
Vol 58 (1) ◽  
pp. 13-19
Author(s):  
António Assunção ◽  
Dina Campos ◽  
Rui Marques ◽  
Inês Cunha ◽  
Patrícia Santos ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Disease Progression ◽  
Clinical Characteristics ◽  
Categorical Variables ◽  
P Value ◽  
Diabetic Patients ◽  
Painful Neuropathy ◽  
Convenience Sample ◽  
Significant Difference ◽  
The Impact

AbstractIntroduction. Diabetic neuropathy (DN) is one of the most devastating complications of diabetes mellitus; however, in contrast to other countries, there are no scientific studies in Portugal evaluating the impact of demographic and clinical characteristics of this pathological entity. The aim of this study was to evaluate the impact of gender, metabolic control, age of diabetic patients, as well as time of disease progression, the appearance of complaints related to neuropathic pain.Material and methods. A multicentre study with a non-probabilistic, convenience sample of 359 patients was performed employing the quantitative method, using the Statistical Package for Social Science 24 software. The p-value of p < 0.05 was defined to consider a result statistically significant. The Spearman correlation coefficient (r) was determined to determine the relationship between categorical variables.Results. There was no statistically significant difference in the prevalence of DN between genders (p = 0.633 and r = 0.025). There was a statistically significant relationship between the value of HbA1c and DN, with p = 0.010 and r = 0.136. There is a relationship between age and complaints of neuropathic pain, with p = 0.034 and r = 0.112. The variable, time of disease progression, is also correlated with the appearance of complaints of neuropathic pain with p = 0.020 and r = 0.112.Conclusion. The prevalence of neuropathic pain in subjects with diabetes is not negligible and is associated with modifiable risk factors that can be identified, possibly modified and prevented. The correct approach for these patients, which involves screening and early treatment, is decisive improving functionality and quality of life.

scholarly journals Efficacy of Cobimetinib in Rosai-Dorfman Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1506-1506
Author(s):  
Jithma P. Abeykoon ◽  
Karen Rech ◽  
Aishwarya Ravindran ◽  
Aldo A. Acosta-Medina ◽  
Saurabh Zanwar ◽  
...  
Keyword(s):  
Disease Progression ◽  
Median Duration ◽  
Research Funding ◽  
Mapk Pathway ◽  
Skin Toxicity ◽  
Advisory Board ◽  
Duration Of Treatment ◽  
Rosai Dorfman Disease ◽  
Grade 3

Abstract INTRODUCTION Rosai-Dorfman disease (RDD) is a rare histiocytic disorder associated with histiocytes expressing high level of macrophage colony stimulating factor receptor (c-fms). Mutations in mitogen-activated protein kinase (MAPK) pathway have been reported in RDD, indicating an underlying clonal process in some patients. Aberrant activation of MAPK pathway can occur due to mutations or high c-fms expression. Data on the use of MAPK/extracellular-signal-related kinase (ERK)-inhibitor therapy in RDD are very limited. Cobimetinib is a MEK inhibitor, which is listed in the National Comprehensive Cancer Network Compendium ® for the treatment of RDD. We present our retrospective experience of cobimetinib treatment in a large series of patients with RDD. METHODS Following approval of the institutional reviewed board, patients (pts) with RDD who were consecutively seen at Mayo Clinic and treated with cobimetinib between 2013-2021 were included. Response was assessed as described by Goyal et al (Haematologica 2020;105:2). Cobimetinib was given 20-60 mg once a day by mouth for 21 days in a 28-day cycle. Adverse events (AEs) were graded using the National Cancer Institute Common Toxicity Criteria v5.0. Time-to-event analyses were calculated from the time of treatment initiation, while duration of response was calculated from the time of 1 st response. Tumor genomic profile was analyzed using Tempus-xT ® assay (Chicago, IL), which includes targeted DNA sequencing (648 oncogenes) and whole transcriptome sequencing. RESULTS Of the 54 pts with RDD, ten were treated with cobimetinib and included in this study. The median follow-up was 16 months (m) [95% confidence interval (CI): 13-not reached (NR)] and most (n=8; 80%) were females. The median age at the time of treatment was 63 years (range: 36-74). Cobimetinib was used as first line therapy in four pts. Overall response rate was 70%, with 30% and 40% achieving complete (CR) and partial (PR) responses, respectively. One had stable disease (SD) and two had progressive disease (PD) (Table 1). The median progression-free-survival was 6.4 m (95%CI: 4.9-NR) and at 6 and 12 m, 67% and 50% of pts remained free from disease progression or death, respectively (Figure 1). The median duration of response was 7.6 m (95%CI: 3.1-NR). At the time of last follow-up, nine (90%) pts were alive. One pt died due to myelodysplastic syndrome with excessive blasts. She had multiple chemotherapy treatments before initiation of cobimetinib. Cobimetinib was discontinued in this pt due to grade 3 anemia and skin toxicity after 6 m of therapy and had SD as the best response. Median duration of treatment for the entire cohort was 6 m (range: 2-14). In the seven pts who responded, the median duration of treatment was 7 m (range: 2-14). Cobimetinib was discontinued in seven pts: disease progression (n=3; one disease progression after achieving PR and two PD while on therapy), grade 3 left ventricular systolic dysfunction (n=1), grade 3 diarrhea (n=1), grade 3 anemia (n=1), and grade 2 creatinine elevation (n=1). Five (50%) pts were started at a reduced dose of cobimetinib at the discretion of treating physician [20 mg (n=4) and 40mg, (n=1)]. Two pts were started at 60 mg and dose reduced to 20 mg after one cycle of treatment due to grade 2 skin toxicity in one and grade 2 skin toxicity and diarrhea in the other. Both pts achieved a PR but progressed after four and six cycles, respectively. One pt started at 40 mg and reduced to 20 mg due to grade 2 skin toxicity after two cycles achieving a PR. The response was sustained in this pt for at least 9 months, until the time of last follow-up (Table 1). Tissue molecular testing showed five pts with MAPK pathway alterations and all of them responded to therapy (CR=3 and PR=2). Of the other five pts who either did not have a MAPK pathway alteration (n=4) or had test failure (n=1), responses were observed in two (40%) pts, both PR (Table 1). CONCLUSION Our study suggests that cobimetinib is an effective treatment in RDD, with responses observed in all pts having MAPK pathway alterations. Less than half of pts without a MAPK pathway alteration achieved a response. However, treatment discontinuations due to AEs were common despite dose reductions. Patients who were treated at low doses of cobimetinib also had remarkable clinical response. Further studies are needed in evaluating other MAPK pathway inhibitors with better toxicity profile to improve adherence and outcomes. Figure 1 Figure 1. Disclosures Tobin: National Institutes of Health: Research Funding; Mayo Clinic Center for MS and Autoimmune Neurology: Research Funding; Mallinckrodt Pharmaceuticals: Research Funding. Bennani: Vividion: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Verastem: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Kymera: Other: Advisory Board. Vassallo: Pfizer: Research Funding; Bristol-Myers-Squibb: Research Funding; Sun Pharma.: Research Funding.

scholarly journals COMPARISON OF CHEMOTHERAPY RESPONSE AND ADVERSE EFFECTS OF DOUBLE-PLATINUM PLUS EGFR-TKI VERSUS DOUBLE-PLATINUM ALONE ON NSLCLC PATIENTS WITH DISEASE PROGRESSION AND EGFR-TKI TREATMENT

2017 ◽  
Vol 53 (4) ◽  
pp. 276
Author(s):  
Laksmi Wulandari ◽  
Edward Pandu Wiriansya
Keyword(s):  
Body Weight ◽  
Adverse Effects ◽  
Disease Progression ◽  
P Value ◽  
Chemotherapy Response ◽  
Subjective Response ◽  
Significant Difference ◽  
Tki Treatment ◽  
Platinum Chemotherapy ◽  
Egfr Tki

EGFR-TKI is the first-line therapy for EGFR-mutant patients. Nevertheless, patients will have disease progression (median PFS 10 – 12 months) due to resistance. The treatment options are still limited in developing countries for such cases, thus double-platinum chemotherapy is the next option. Although IMPRESS study reported no difference in terms of PFS and OS between double-platinum alone and double-platinum plus EGFR-TKI, several local studies reported benefit of continuing EGFR-TKI in combination with double-platinum chemotherapy (treatment beyond progression). This study aimed to compare chemotherapy effects of double-platinum plus EGFR-TKI versus double-platinum alone on patients with NSCLC progression after EGFR-TKI treatment. This was an analytical descriptive study using prospective cohort design, involving 30 patients with disease progression following EGFR-TKI treatment that met inclusion criteria in Dr. Soetomo Hospital. Subjects were divided into two groups: arm A (double-platinum plus EGFR-TKI) and arm B (double-platinum alone). Subjects were observed until 4 cycles of double-platinum chemotherapy. Subjective response (body weight and EQ5D questionnaire) was analyzed, chest CT scans were evaluated using RECIST criteria, and adverse effects were monitored. This study was conducted in accordance with GCP principles and has received ethics certificate from Dr. Soetomo Hospital ethics committee (No. 08/Panke.KKE/I/2017). The results showed that subject characteristics between two arms were insignificantly different (p=0.05). The most common EGFR mutation was exon 21 (50% on arm A and 60% on arm B). Chi square was tested on subjective response parameter (EQ5D (p=0.483)). T2 free sample was tested on semi-subjective parameter (body weight (p=1.00)). Comparison test on both groups after cycle 2 and 4 showed p value=0.05. Statistical test on adverse effect between both groups showed p value=0.526. As a conclusion, there was no significant difference between double-platinum and double-platinum plus EGFR-TKI on patients who had disease progression following EGFR-TKI treatment.

scholarly journals 288. Follow-Up Blood Cultures in Gram-Negative Bacteremia: How Do They Impact Outcomes

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S144-S144
Author(s):  
Azza Elamin ◽  
Faisal Khan ◽  
Ali Abunayla ◽  
Rajasekhar Jagarlamudi ◽  
aditee Dash
Keyword(s):  
Clinical Outcomes ◽  
Antibiotic Treatment ◽  
Readmission Rate ◽  
Blood Cultures ◽  
Categorical Variables ◽  
Gram Negative ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

Abstract Background As opposed to Staphylococcus. aureus bacteremia, there are no guidelines to recommend repeating blood cultures in Gram-negative bacilli bacteremia (GNB). Several studies have questioned the utility of follow-up blood cultures (FUBCs) in GNB, but the impact of this practice on clinical outcomes is not fully understood. Our aim was to study the practice of obtaining FUBCs in GNB at our institution and to assess it’s impact on clinical outcomes. Methods We conducted a retrospective, single-center study of adult patients, ≥ 18 years of age admitted with GNB between January 2017 and December 2018. We aimed to compare clinical outcomes in those with and without FUBCs. Data collected included demographics, comorbidities, presumed source of bacteremia and need for intensive care unit (ICU) admission. Presence of fever, hypotension /shock and white blood cell (WBC) count on the day of FUBC was recorded. The primary objective was to compare 30-day mortality between the two groups. Secondary objectives were to compare differences in 30-day readmission rate, hospital length of stay (LOS) and duration of antibiotic treatment. Mean and standard deviation were used for continuous variables, frequency and proportion were used for categorical variables. P-value &lt; 0.05 was defined as statistically significant. Results 482 patients were included, and of these, 321 (67%) had FUBCs. 96% of FUBCs were negative and 2.8% had persistent bacteremia. There was no significant difference in 30-day mortality between those with and without FUBCs (2.9% and 2.7% respectively), or in 30-day readmission rate (21.4% and 23.4% respectively). In patients with FUBCs compared to those without FUBCs, hospital LOS was longer (7 days vs 5 days, P &lt; 0.001), and mean duration of antibiotic treatment was longer (14 days vs 11 days, P &lt; 0.001). A higher number of patients with FUBCs needed ICU care compared to those without FUBCs (41.4% and 25.5% respectively, P &lt; 0.001) Microbiology of index blood culture in those with and without FUBCs Outcomes in those with and without FUBCs FUBCs characteristics Conclusion Obtaining FUBCs in GNB had no impact on 30-day mortality or 30-day readmission rate. It was associated with longer LOS and antibiotic duration. Our findings suggest that FUBCs in GNB are low yield and may not be recommended in all patients. Prospective studies are needed to further examine the utility of this practice in GNB. Disclosures All Authors: No reported disclosures

scholarly journals LGG-18. EVEROLIMUS TREATMENT IN PEDIATRIC PATIENTS AFFECTED BY LOW-GRADE GLIOMAS (pLGG) NON-TSC, BRAF v600-WT

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii369-iii369
Author(s):  
Antonella Cacchione ◽  
Evelina Miele ◽  
Maria Chiara Lodi ◽  
Andrea Carai ◽  
Giovanna Stefania Colafati ◽  
...  
Keyword(s):  
Adverse Event ◽  
Disease Progression ◽  
Mapk Pathway ◽  
Brain Mri ◽  
Mammalian Target Of Rapamycin ◽  
Low Grade ◽  
Duration Of Treatment ◽  
Tumor Biopsy ◽  
Low Grade Gliomas ◽  
Personalized Approach

Abstract BACKGROUND MAPK pathway is the hallmark of pediatric low grade gliomas (pLGGs); hyperactivation of mTOR (mammalian target of rapamycin) might be a suitable biomarker for therapeutic response. We investigated the feasibility of Everolimus, mTOR inhibitor, in patients affected by pLGGs. METHODS Patients 1 to 18 years old, diagnosed with pLGG, with a positive tumor biopsy for mTOR/phospho-mTOR and radiological and / or clinical disease progression, treated at Bambino Gesù Children’s Hospital in Rome were evaluated. Tumor DNA methylation analysis was performed in 10 cases. Exclusion criteria included: Tuberous Sclerosis patients, Sub Ependymal Giant Astrocytoma. Everolimus was administered orally at a dose of 2.5 mg or 5 mg daily based on body weight. Patients were evaluated with brain MRI every 4, 8 and 12 months after treatment start and every six months thereafter. RESULTS 16 patients were enrolled from September 2014 and 2019. The median age was 7.5 years old. All patients had at least one adverse event. Events rated as severe (grade 3/4) were reported in 6 patients. Stomatitis was the most frequent adverse event. One patient discontinued treatment due to grade 4 toxicity (ulcerative stomatitis and fatigue). The median duration of treatment was 21 months (4–57 months). Brain MRI evaluations have showed disease stability in 11 patients, partial response in 2 patients and disease progression in 3 patients. CONCLUSIONS Everolimus has proven to be well tolerated and effective treatment in terms of disease stability in patients with pLGGs. It’s also an excellent example of chemo-free personalized approach.

scholarly journals 651. Comparative Analysis Between Bacterial And Fungal Malignant Otitis Externa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S383-S384
Author(s):  
Fatma Hammami ◽  
Makram Koubaa ◽  
Amal Chakroun ◽  
Fatma Smaoui ◽  
Khaoula Rekik ◽  
...  
Keyword(s):  
Otitis Externa ◽  
Clinical Presentation ◽  
The Elderly ◽  
Causative Organism ◽  
Diabetic Patients ◽  
Duration Of Treatment ◽  
Evolutionary Features ◽  
Significant Difference ◽  
Malignant Otitis Externa ◽  
History Of

Abstract Background Malignant otitis externa is a fatal infection of the external ear and temporal bone. Pseudomonas aeruginosa is the most common causative organism, while fungi are a rare cause of malignant otitis externa. We aimed to compare the clinical, therapeutic and evolutionary features between bacterial and fungal malignant otitis externa. Methods We conducted a retrospective study including all patients hospitalized for malignant otitis externa in the infectious diseases department between 2000 and 2018. Results Overall, we encountered 82 cases of malignant otitis externa, among which there were 54 cases (65.9%) of bacterial malignant otitis externa (BMO) and 28 cases (34.1%) of fungal malignant otitis externa (FMO). The males were predominant among BMO cases (57.4% vs 50%; p=0.5). Patients with FMO were significantly older (70±9 years vs 61±10 years; p&lt; 0.001) and had medical history of diabetes mellitus more frequently (96.4% vs 77.8%; p=0.03). The use of topical corticosteroids was significantly more reported among FMO cases (28.6% vs 5.6%; p=0.006). Otalgia (96.4% vs 81.5%), otorrhea (75% vs 66.7%) and cephalalgia (46.4% vs 42.6%) were the revealing symptoms among FMO and BMO, respectively, with no significant difference. Tenderness to palpation of the mastoid bone (64.3% vs 38.9%; p=0.02) and stenosis of the external auditory canal (92.9% vs 72.2%; p=0.02) were significantly more frequent among FMO cases. Complications were significantly more frequent among FMO cases (42.9% vs 9.3%; p&lt; 0.001). Treatment duration was significantly longer among FMO cases (70[40-90] days vs 45[34-75] days; p=0.03). Conclusion Our study showed that FMO affected more frequently the elderly and diabetic patients, when compared with BMO. Regardless of the causative agent, the clinical presentation was similar. However, the outcome was poor among FMO cases with the occurrence of complications, requiring a longer duration of treatment. Disclosures All Authors: No reported disclosures

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