scholarly journals Descriptive Analysis of Azacitidine Use in Four Adult University Teaching Hospitals in Quebec, Canada

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5244-5244
Author(s):  
Ghislain Bérard ◽  
Nathalie Marcotte ◽  
Marie-Claude Michel ◽  
Paul Farand ◽  
Louise Deschenes ◽  
...  
Keyword(s):  
Adverse Events ◽  
Median Time ◽  
Stable Disease ◽  
Real Life ◽  
Management Program ◽  
University Teaching ◽  
Teaching Hospitals ◽  
International Prognostic Scoring System ◽  
Therapeutic Drug ◽  
University Hospitals

Abstract Background: Azacitidine (5-AZA; Vidaza®), a pyrimidine nucleoside analog, is used in the treatment of myelodysplastic syndrome (MDS) and other hematological malignancies. Pharmacy directors gave the Therapeutic Drug Management Program (TDMP - www.pgtm.qc.ca) the mandate to evaluate 5-AZA use in four University Hospitals in Quebec, Canada. Objectives: Describe and review 5-AZA use for all indications in our hospitals. Methods: A review of pharmacy databases was performed to identify patients who received 5-AZA between January 1st 2010 and May 31st 2013. Files and medical records of every patient who received 5-AZA during the study period were reviewed to assess diagnostic (including International Prognostic Scoring System (IPSS) scores), treatment, response and non-hematological adverse events. Results: A total of 77 patients received 5-AZA during the study period, 56 (72.7 %) for the treatment of MDS, 15 (19.5 %) for acute myeloid leukemia (AML) and 6 (7.8 %) for chronic myelomonocytic leukemia (CMML). At the end of the study period, 31 patients were alive (14 were still on treatment), 35 patients had died and 11 were lost to follow up. Excluding the 14 patients still on treatment, 32 patients (50.8 %) received at least 6 cycles of 5-AZA. In the MDS population (76.7 % with an intermediate-2 or higher IPSS score), patients received a mean of 8.0 cycles (median = 6) and the overall benefit rate (OBR) (complete remission, partial remission, hematological improvement or stable disease) was 48.2 %. The median overall survival (OS) was 17.8 months and the median time to progression (TTP) was 9.7 months. MDS transformation to AML occurred in 16 patients after a mean of 9.9 months. Median time to transformation or death in the MDS population was 14.4 months. In the AML population, patients received a mean of 6.6 cycles (median = 5) and the OBR was 26.7 %. The median OS was 12.2 months and the median TTP was 6.5 months. In the CMML population, patients received a mean of 10 cycles (median = 5.5) and the OBR was 50% (3 of the 6 patients achieved stable disease). Across all patient populations, a 5-AZA dose of 75 mg/m2 for 7 days every 28 days was used in 77.8% of patients. Non-hematological adverse events were seen in 67 patients (87 %) but were mostly mild and most did not lead to delays or dose reductions (treatment intensity of 96 %). Conclusions: Our results show that 5-AZA had a more limited benefit in our real-life population when compared to published clinical trials (OBR of 44.2 % in MDS, AML and CMML populations combined compared to 60% and 61% and a mean exposition of 8.1 months compared to 10.3 to 11.4 months in the pivotal clinical studies (AZA-001 and CALGB 9221 respectively)). Considering that 5-AZA is often the only treatment we can offer these patients and considering its high cost, it would be of highest importance to wisely choose patients to whom we offer this treatment and to periodically re-evaluate its use (at least after the 6th cycle) to confirm the patient is benefiting from treatment. Disclosures Olney: Cellgene: Honoraria; Pfizer: Consultancy; BMS: Consultancy; Novartis: Consultancy.

Real-life use of nivolumab and pembrolizumab in four adult university teaching hospitals in Québec, Canada.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14125-e14125 ◽  
Author(s):  
Nathalie Letarte ◽  
Layal El Raichani ◽  
Chantal Guevremont ◽  
Nathalie Marcotte ◽  
Ghislain Berard ◽  
...  
Keyword(s):  
General Population ◽  
Adverse Events ◽  
Real Life ◽  
Median Number ◽  
University Teaching ◽  
Teaching Hospitals ◽  
Grade 3 ◽  
Nsclc Patients ◽  
University Teaching Hospitals

e14125 Background: Nivolumab and pembrolizumab, two anti-PD1 agents, were approved and funded in Québec since 2016 for non small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and melanoma. The objectives were to describe and assess the “real-life” use, efficacy and security of nivolumab and pembrolizumab in NSCLC, RCC and melanoma in the general population. Methods: Medical records of every patient who received nivolumab or pembrolizumab between January 1st 2011 and October 31st 2017 were reviewed retrospectively. Data analysis cut-off was Dec 31st 2017. Results: In total, 532 patients received at least one dose of anti-PD1 during the study period. Median number of doses received varied for each indication (medians varied from 4 to 9.5). Adverse events were pooled together by drug. 47.7 % of patients receiving pembrolizumab suffered from any grade immune-related adverse event (IRAE), most of them of grade 1 or 2. 12.2 % of patients reported grade 3-4 IRAE. Most of the patients reported only one type of IRAE. For nivolumab, 44.6% of patients presented with any IRAE, including 8.3% of grade 3-4. Dermatologic IRAE were more frequent in the melanoma patients whereas gastrointestinal and pulmonary IRAE were more frequent in NSCLC patients. Treatment discontinuation due to adverse events varied from 6 to18% depending on indication. Conclusions: Nivolumab and pembrolizumab seemed less effective and caused more IRAE in “real-life” population than in the pivotal clinical trials. Caution and regular follow-up are warranted when using these drugs in general population. Longer follow-up is needed.[Table: see text]

A pilot clinical trial of p53/p16-independent epigenetic therapy for pancreatic ductal adenocarcinoma (PDA).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 699-699
Author(s):  
Davendra Sohal ◽  
Smitha S. Krishnamurthi ◽  
Rita Tohme ◽  
Dale Randall Shepard ◽  
Alok A. Khorana ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Median Time ◽  
Dna Methyltransferase ◽  
Cleveland Clinic ◽  
Ductal Adenocarcinoma ◽  
Epigenetic Therapy ◽  
University Hospitals ◽  
Open Label ◽  
Ecog Ps

699 Background: PDA treatment is limited to cytotoxic drugs. A key factor limiting their efficacy is TP53 mutations, omnipresent in PDA, which counter apoptosis-mediated cell kill. We evaluated a novel epigenetic approach using decitabine (Dec) to inhibit DNA methyltransferase 1 (DNMT1) and effect cancer cell cycle exits by epithelial-differentiation, combined with tetrahydrouridine (THU) to inhibit cytidine deaminase (CDA) and thereby permit oral bioavailability and solid-tissue distribution of Dec. Methods: Open-label single-arm, IRB-approved clinical trial at Cleveland Clinic and University Hospitals for patients with metastatic PDA that had progressed on prior chemotherapy, ECOG PS of 0-2. Treatment was oral, weight-based, with Dec 10-20 mg, and THU 500-1000 mg daily, 5 days/week. Primary endpoint was DNMT1 protein levels at 16-week vs baseline biopsies. Results: From Apr to Aug 2017, we enrolled 13 patients. Median age was 65 (range 44-74) years; 7 (54%) males; 11 (85%) Caucasians. Median time from diagnosis was 13 (3.9-53.5) months, with a median of 2 (1-3) prior lines of therapy. Baseline ECOG PS was 0/1 in 12 (92%) patients. All patients started study drugs; median time on treatment was 35 (4-63) days, and on study 72 (25-105) days. The most frequent adverse events attributable to the study drugs were anemia (n=5), and anorexia, dehydration, nausea, fatigue, febrile neutropenia and decreased lymphocyte count, in 3 patients each; no deaths. Eight (62%) patients underwent evaluation scans at 8 weeks, showing stable disease in 1 patient and progression in 7. Common reasons for coming off of study drugs were progression (n=6), physician discretion (n=3), and adverse events (n=2). Overall, 6 patients died; median survival was 3.1 months, and patients did not reach the 16-week biopsy. Shifts in blood counts, a sensitive indicator of Dec systemic activity, were unexpectedly mild, and plasma CDA enzyme activity was increased versus other cancer and normal controls. Conclusions: This first-of-its-kind study demonstrated feasibility and safety of the novel oral epigenetic therapy. Systemically elevated CDA in these patients requires higher doses of THU; a trial accordingly refined is planned. Clinical trial information: NCT02847000.

scholarly journals Interest of Dosing of Ibrutinib in B-Cell Lymphoid Malignancies: Data from a Real-Life, Phase 4 Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3960-3960
Author(s):  
Anne Calleja ◽  
Sandra De Barros ◽  
Camille Vinson ◽  
Caroline Protin ◽  
Lucie Oberic ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Plasma Concentrations ◽  
Real Life ◽  
Therapeutic Drug ◽  
Therapeutic Effects ◽  
Lymphoid Malignancies ◽  
Oncology Nurse ◽  
Drug Concentrations

Abstract Introduction: Therapeutic drug monitoring (TDM) entails the measurement of drug concentrations and the individualization of drug dosages or schedules to maximize therapeutic effects and minimize toxicity. Ibrutinib (IBR), the first-in-class inhibitor of BTK (Bruton tyrosine kinase) is approved for the therapy of relapsed/refractory chronic lymphocytic leukemia (R/R CLL), mantle cell lymphoma (MCL) and Waldenström's disease (WM), at the dose of 420-560mg/d. Drug-drug interactions (DDI), older age, liver diseases have been reported to impact PK parameters of ibrutinib, but dosing is not yet part of clinical practice, despite TDM of imatinib and other kinase inhibitors is routinely used in chronic myeloid leukemia. In this study, we sought to determine whether TDM of ibrutinib should be proposed for patients, in a preliminary cohort of 73 patients included in the PK-e3i trial (NCT02824159). Methods: Serial plasma PK samples were collected at steady-state after one month of therapy in 73 patients: before intake (residual concentration), and then at time 0.5-1-2-4-6h. Key PK parameters for ibrutinib and its metabolite DHD-ibrutinib were calculated: Cmax, Cmin, tmax,AUC24h. Analysis of DDI was made by an oncology pharmacist in 49/73 patients. Treatment-related adverse events were monitored by phonecalls given by an oncology nurse (AMA procedure) and during consultations with hematologist (at least twice a month the first 6 months, then monthly until 12 months, then every 3 months), and severity graded according CTCAE version 4 scale. Efficacy of therapy in CLL patients was assessed with an "effect marker" to demonstrate biological efficacy, the redistribution hyperlymphocytosis seen in 70% of patients the first month of therapy. Results: we reported very similar PK results for ibrutinib as compared to pivotal phase 1 trials in CLL and other B-cell lymphoid malignancies (Advani RH, J Clin Oncol 2013, Byrd JC, New Engl J Med 2013). Mean peak plasma concentrations were observed 1-2h after dosing, Cmax and AUC results showing an important inter-patient heterogeneity. Median Cmax was 150ng/ml (8.2-596ng/ml), and median AUC24h was 412.4 ng h/mL ((32.2-2906 ng h/mL). According to published phase I trials, complete or near complete BTK occupancy was observed in patients with AUCs exceeding 160 ng h/mL, suggesting ibrutinib dose might have been supramaximal in 67 of our patients. Adverse events the first 3 months were seen in 96% (grade 1), 63% (grade 2), 25% (grade 3) and 6.5% (grade 4), respectively. We plotted AUC results for the total cohort of 73 patients (Figure 1), and for 49 patients with adverse events monitoring available at 3 months (9/49 needed drug dose reduction due to toxicity) (Figure 2), both emphasizing the absence of correlations between AUC levels and toxicities. We next splited up toxicities into 10 sub-groups (bleeding, cardiac, liver, muscle, joint, skin, infection, gastro-intestinal, hematologic, neurologic disorders). Again, we could not identify a specific organ toxicity associated with a significant increase of Cmax or AUC24h, nor we could identify a specific DDI signature explaining side effects in our patents (data not shown: 13/49 had CYP3A4 inhibitors, 25/49 had pgp inhibitors). In 45 CLL patients with PK parameters and lymphocyte counts available after one month of therapy, we made the intriguing observation that lower Cmax correlated with the lack of observable, transient hyperlymphocytosis (a class-effect of ibrutinib, correlating with PFS in the Resonate trial) (Figure 3). Altogether, our data did not find any positive correlation between high ibrutinib exposure and efficacy or safety profile. Conclusions: our preliminary results suggested that higher Cmax and AUC24h did not correlate neither to efficacy nor to classical toxicities reported with ibrutinib intake. On one hand, we think that dosing intra-cellular concentrations could be more reliable than in plasma. On the other hand, we could consider TDM of ibrutinib in the context of a clinical trial reducing the doses of drug over time, to limit clinical and financial toxicity of this highly efficient drug. Disclosures No relevant conflicts of interest to declare.

scholarly journals Descriptive Analysis of Bortezomib Use in Multiple Myeloma in Four Adult University Teaching Hospitals in Quebec, Canada

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5573-5573
Author(s):  
Nathalie Marcotte ◽  
Marie-Claude Michel ◽  
Louise Deschenes ◽  
Nathalie Letarte ◽  
Daniel Froment ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Disease Progression ◽  
26S Proteasome ◽  
University Teaching ◽  
Therapeutic Drug ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
Lymphoplasmacytic Lymphoma ◽  
Off Label

Abstract Background: Bortezomib, a reversible inhibitor of the 26S proteasome widely used in the treatment of multiple myeloma, is now being used in various other indications. Pharmacy directors gave the Therapeutic Drug Management Program (TDMP - www.pgtm.qc.ca) the mandate to evaluate bortezomib use in four University Hospitals in Quebec, Canada. Objectives: Describe bortezomib use for all indications in our hospitals and review its utilisation in the treatment of multiple myeloma. Methods: A review of pharmacy databases was performed to identify patients who received bortezomib between June1st 2012 and May 31st 2013. The pharmaceutical and medical records of every patient who received bortezomib were reviewed to assess the treatment, pathology and adverse events. Results: Two hundred and thirty two bortezomib regimens were administered to 227 different patients during the study period. Median age was 68. The most frequent indication (55%) was first-line treatment of multiple myeloma (n=128) followed by treatment of relapsed/refractory disease (31%) (n=73). Various other indications, including amyloidosis (n=17), lymphoplasmacytic lymphoma (n=12) and mantle cell lymphoma (n=2), represented 13% of the population. At the time of data analysis, 35% of patients were still treated with bortezomib, 25% had finished their planned treatment and 34% had discontinued treatment because of adverse events or disease progression. Fifteen patients (6%) died during the study period. Among the 45 patients eligible for autologous stem cell transplant (ASCT), the main regimen used was the association of bortezomib and dexamethasone (VelDex) (n=27), primarily using subcutaneous bortezomib (n=24) at 1.3 mg/m2 (n=30). Median treatment duration was four cycles. Twenty-eight patients have undergone ASCT and only two progressed. The association of bortezomib, melphalan and prednisone (VMP) (54.2%) followed by VelDex (29%) and the association of cyclophosphamide, bortezomib and dexamethasone (CyborD) (16.8%) were the regimens used in the population (n=83) not eligible to ASCT. Response rate using international uniform response criteria for multiple myeloma was 47.9% excluding patients still receiving treatment at the time of data collection. Seventy three patients received bortezomib for relapsed/refractory myeloma. Of these patients, thirty two (43.8%) discontinued therapy, nineteen due to disease progression, eight for the occurrence of side effects and five for other reasons. The initial dose was variable, from 1.0 to 1.6 mg/m2, and close to half of this patient population received CYBorD (49.4%), followed by VelDex (30.2%) and VMP protocols (15%). The number of cycles for patients who completed treatment (4 to 9) as well as the median exposure time (57 to 223 days) was also highly variable. Respectively 8.5% and 10.9% of the population treated with bortezomib for multiple myeloma were hospitalized (n=17) or had to discontinue treatment (n=22) because of adverse events (mostly hematologic toxicity, peripheral neuropathy or gastro-intestinal toxicity). Conclusions: Bortezomib is widely used in the treatment of multiple myeloma. Treatment algorithms should be developed and implemented to optimize the use of bortezomib, particularly in the relapsed/refractory setting. Standard regimens should also be implemented in each center. The utilisation of pre-printed orders for the prescription of chemotherapy regimens promotes uniform prescription. A review of the literature should be performed and recommendations should be made for the use of bortezomib in off-label indications like amyloidosis and lymphoplasmacytic lymphoma. Disclosures Off Label Use: bortezomib use in amyloidosis and lymphoplasmacitic lymphoma. Lemieux-Blanchard:celgene: Membership on an entity's Board of Directors or advisory committees; Amgen and Janssen: Other: preceptorship. Bérard:Janssen: Honoraria. Sebag:Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria.

Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer.

1998 ◽  
Vol 16 (11) ◽  
pp. 3649-3655 ◽  
Author(s):  
D R Miller ◽  
G T Anderson ◽  
J J Stark ◽  
J L Granick ◽  
D Richardson
Keyword(s):  
Quality Of Life ◽  
Cancer Therapy ◽  
Adverse Events ◽  
Tumor Progression ◽  
Median Time ◽  
Stable Disease ◽  
Safety And Efficacy ◽  
Shark Cartilage ◽  
Time To Tumor Progression

PURPOSE Patients with cancer and chronic inflammatory disorders have used shark cartilage (SC) preparations for many years. Preclinical studies that support their beneficial effects are scanty, and reports of clinical trials have been anecdotal. The proposed mechanisms of antitumor action include direct or indirect inhibition of angiogenesis. Because of the emerging use of SC as an alternative to conventional cancer therapy, this trial was launched to evaluate the safety and efficacy of SC. PATIENTS AND METHODS Sixty adult patients with advanced previously treated cancer (breast, 16 patients; colorectal, 16 patients; lung, 14 patients; prostate, eight patients; non-Hodgkin lymphoma, three patients; brain, one patient; and unknown primary tumor, two patients) were enrolled. Eligibility criteria included confirmation of diagnosis, resistance to conventional therapy, objective measurable disease, life expectancy of 12 weeks or greater, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, no recent or concomitant anticancer therapy, no prior SC, and informed consent. Patients underwent evaluation of the extent of disease, quality-of-life score (Functional Assessment of Cancer Therapy-General [FACT-G] scale), and hematologic, biochemical, and selected immune function studies at baseline and after 6 and 12 weeks of SC therapy. The dose of SC was 1 g/kg daily orally in three divided doses. Standard criteria were used to evaluate adverse events and response. RESULTS Ten of 60 patients were lost to follow-up(LTFU) or refused further treatment (RFT) before the 6-week evaluation and were not assessable for toxicity and response. Three patients with stable disease at 6 weeks were LTFU or RFT thereafter. Of the 47 fully assessable patients, five were taken off study because of gastrointestinal toxicity or intolerance to SC. Progressive disease (PD) at 6 or 12 weeks occurred in 22 and five patients, respectively. Five patients died of PD while undergoing SC therapy. No complete (CRs) or partial responses (PRs) were noted. Median time to tumor progression in the entire study population was 7+/-9.7 weeks (mean, 11.4 weeks; range, 3.7 to 45.7 weeks). Ten (20%) of 50 assessable patients, or 16.7% of the 60 intent-to-treat patients, had stable disease (SD) for 12 weeks or more. The median time to tumor progression was 27 weeks, the mean was 28.8+/-9.9 weeks, and the range was 18.6 to 45.7 weeks. In this subset, FACT-G scores improved in four patients, were unchanged in four patients, and declined in two patients. Twenty-one adverse events (grade 1, eight events; grade 2, seven events; and grade 3, six events) were recorded, 14 of which were gastroenterologic (nausea, vomiting, constipation). CONCLUSION Under the specific conditions of this study, SC as a single agent was inactive in patients with advanced-stage cancer and had no salutary effect on quality of life. The 16.7% rate of SD was similar to results in patients with advanced cancer treated with supportive care alone.

Descriptive Analysis and Review of Utilization of Rituximab In the Maintenance Treatment of Non-Hodgkin's Lymphoma In Five University Teaching Hospitals In Quebec, Canada.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1511-1511
Author(s):  
Nathalie Letarte ◽  
France Varin ◽  
Daniel Froment ◽  
Elaine Pelletier ◽  
Benoit Bailey ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Disease Progression ◽  
Maintenance Treatment ◽  
B Cell Lymphoma ◽  
University Teaching ◽  
Teaching Hospitals ◽  
Therapeutic Drug ◽  
Lymphoid Leukemia ◽  
Off Label

Abstract Abstract 1511 Background: Rituximab, a monoclonal antibody targeting CD20 receptors widely used in the treatment of non-hodgkin lymphoma, is now being used in various indications, on and off-label. For five University Hospitals in Quebec, Canada, rituximab represents more than 10% of the total drug expenses. Pharmacy managers gave the Therapeutic Drug Management Program (TDMP – www.pgtm.qc.ca) the mandate to evaluate rituximab use in those centers. Objectives: The objectives of the study were to describe rituximab use for all indications in our hospitals and to review the utilization of rituximab in maintenance therapy for follicular lymphoma according to predefined criteria. Methods: A review of pharmacy databases was performed to identify patients who received rituximab between April 1st 2008 and March 31st 2009. Every patient file containing rituximab was reviewed. Patients’ medical records were also reviewed for pathology and side effects. No sampling was performed. Results: At least one dose of rituximab was administered to 797 adult patients during the study period. Median age was 62. The most frequent indications were follicular lymphoma (36%) and diffuse large B-cell lymphoma (26%) followed by chronic lymphoid leukemia (CLL) (8%). Various off label indications, including idiopathic thrombocytopenic purpura, hemolytic anemia and Waldenstrom macroglobulinemia, represented 30% of our population. At the time of data analysis, 42% of patients were still treated with rituximab, 45% had finished their planned treatment and 6% had discontinued treatment because of adverse events or disease progression. Thirty-eight patients (4.8%) died during the study period. Rituximab was also used in 41 pediatric patients for various indications, mostly for nephrotic syndrome (27%). The evaluation of patients outcome for off-label indications could not be performed due to the complexity, variety and chronic courses of diseases treated. For the 232 patients receiving rituximab as maintenance therapy, only 76% of patients had follicular lymphoma. Of these, 53% received rituximab maintenance after first-line treatment with R-CVP and 19% after R-CHOP. Only one patient receiving maintenance treatment stopped therapy because of disease progression. No death was reported. Conformity to utilization criteria was excellent for dose and frequency (100% and 99%) but lower for duration and indication (87 % and 70%). Of note, 13% exceeded the planned two years treatment length and fourteen patients received maintenance therapy following induction chemotherapy for CLL. Conclusions: Rituximab was used in various on and off label indications and utilization criteria should be developed and followed in each centers. Pharmacy and therapeutics committees should also request an annual summary of efficacy and security for the off-label indications. Almost a third of patients treated with maintenance rituximab did not receive it for follicular lymphoma. A review of the literature should be performed and recommendations be made for other indications for maintenance treatment. Disclosures: Off Label Use: review of utilisation or rituximab: non hematologic indications.

scholarly journals Outcomes of Patients with Myelodysplastic Syndromes (MDS) Who Achieve Stable Disease after Treatment with Hypomethylating Agents (HMA)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3273-3273 ◽  
Author(s):  
Aziz Nazha ◽  
Mikkael A. Sekeres ◽  
Guillermo Garcia-Manero ◽  
John Barnard ◽  
Najla H Al Ali ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Median Time ◽  
Stable Disease ◽  
Conflicts Of Interest ◽  
Initial Assessment ◽  
International Prognostic Scoring System ◽  
Fisher Exact Test ◽  
Best Response ◽  
Similar Survival

Abstract Background The primary treatment goal in higher-risk MDS patients (pts) is to prolong survival by altering the natural history of the disease and delaying progression to acute myeloid leukemia (AML). Treatment with HMA such as azacitidine (AZA) improves overall survival (OS) in pts who achieve a response of stable disease (SD) or better (complete remission [CR], partial remission [PR], or hematologic improvement [HI]) (Gore et al, Haematologica, 2013). However, it is not well established if pts who achieve SD by 6 months (mo) of therapy should be offered different therapies to optimize their response or continue with the same HMA regimen. Methods Clinical data were obtained from the MDS Clinical Research Consortium database. Pts treated with either AZA or decitabine (DAC) were included and categorized per the Revised International Prognostic Scoring System. Responses were evaluated per International Working Group (IWG 2006) criteria. SD was defined as no evidence of progression and without achievement of HI. Early response was defined as achievement of CR, PR, HI, or SD between 3-6 months (mo) of therapy. Best response was assessed after 6 mo of treatment. OS was calculated from the start of therapy to date of death or last follow up. Differences were evaluated using the Fisher-exact test and Mann-Whitney U tests for categorical and continuous variables, respectively. Results Of 291 pts with higher-risk MDS and available response data, 248 (85%) received treatment with AZA and 43 (15%) with DAC. Median age was 70 years (range, 35-99), median absolute neutrophil count (ANC) was 1.05 X109/L (range, .58-68), hemoglobin 9.3 g/dL (range, 3.7-14.3), platelets 73 X109/L (range, 4-659), and bone marrow blasts 10% (range, 0-19). Per IPSS-R, 20% of pts were intermediate risk, 37% high, and 43% very high. A total of 142 pts (49%) progressed to AML. Median time from diagnosis to start of HMA was 28 days. Early responses (3-6 mo) were: CR 10%, PR 5%, HI 10%, and SD 49%. Among the 144 pts who achieved SD at 3-6 mo, 29 (20%) achieved a better response (CR, PR, or HI) later during their treatment, with a median time to better response of 3.7 mo (range,1.2-14.5); 113 (89%) remained with stable disease, and 2 (1%) progressed to AML. With a median follow up of 16.5 mo (range, 2.5-120.2), the median OS by best response at any time point during therapy: CR 19.7 mo, PR 12.6 mo, HI 15.4 mo, and SD 13.8 mo. Pts who achieved CR had superior OS compared to SD (p=.03) but similar survival compared to pts who achieved PR (p=.45) or HI (p=.24). Of 29 pts with SD who achieved a better response > 6 mo, 16 (55%) achieved a CR and 13 (45%) achieved a PR or HI. Pts with SD who subsequently achieved CR had superior OS compared to pts who remained in SD (28.1 vs 14.4 mo, respectively, p=.04), while pts who subsequently achieved PR or HI had a similar survival compared to pts who remained in SD (12.1 vs 14.4 mo, respectively, p=.81). Conclusion Among MDS pts treated with HMAs, 20% who have SD at initial assessment go on to have a better response later in their treatment course, However, only 11% of SD pts achieved a CR thereafter, which predicted better OS. Thus, pts who achieve SD by 6 mo should be offered a clinical trial with novel agents to improve their chances of achieving CR. If a clinical trial is not available, pts should remain on HMA therapy until disease progression. Disclosures No relevant conflicts of interest to declare.

L'esperienza clinica con Levometadone nel trattamento del disturbo da uso di oppiacei

MISSION ◽  
2019 ◽  
pp. 54-57
Author(s):  
Marco Riglietta ◽  
Paolo Donadoni ◽  
Grazia Carbone ◽  
Caterina Pisoni ◽  
Franca Colombi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Real Life ◽  
Opioid Use Disorder ◽  
Racemic Mixture ◽  
Opioid Use ◽  
The Real ◽  
New Formulation

In Italy, at the end of the 1970s, methadone hydrochloride was introduced for the treatment of opioid use disorder, in the form of a racemic mixture consisting of levomethadone and dextromethadone.In 2015 Levometadone was introduced, a new formulation marketed in Italy for the treatment of opioid use disorder in 2015.The article aims to bring the experience of an Italian Addiction Centre back to the use of this new formulation in the "real life" analyzing the efficacy, the trend of adverse events and pharmacological iterations in a context in which the treated population often uses besides the opiates, cocaine and alcohol, are burdened by a relevant physical and psychic comorbidity and frequently have a prescribed polypharmacy.

657 Interleukin-6 receptor blockade for management of immune checkpoint inhibitor related adverse events in patients with melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A694-A694
Author(s):  
Chantal Saberian ◽  
Faisal Fa’ak ◽  
Jean Tayar ◽  
Maryam Buni ◽  
Sang Kim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Median Time ◽  
Interleukin 6 ◽  
Immune Checkpoint ◽  
Activity Index ◽  
Critical Role ◽  
Cancer Center ◽  
Interleukin 6 Receptor ◽  
Md Anderson

BackgroundManagement of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood there is enough evidence that IL-6 induced Th-17 that may play critical role in the pathogenesis. Herein, we describe our clinical experience using interleukin-6 receptor (IL-6R) blockade in management of irAEs in melanoma patients.MethodsWe searched MD Anderson databases to identify cancer patients who had received ICIs between January 2004 and March 2020. Of 11,391 ICI-treated patients, 21 patients with melanoma who received IL-6R blockade after ICI infusion were identified and their medical records were reviewed.ResultsMedian age was 61 years (41–82), 52% were females, 90% received anti-programmed cell death-1 antibodies. Fourteen patients (67%) had de novo onset irAEs (11 had arthritis, and 1 each with polymyalgia rheumatica, oral mucositis, and CNS vasculitis), and 7 patients (33%) had flare of their pre-existing autoimmune diseases (5 had had rheumatoid arthritis, and 1 each with myasthenia gravis and Crohn’s disease). Median time from ICI initiation to irAEs was 91 days (range, 1–496) and to initiation of IL-6R blockade was 6.6 months (range, 0.6–24.3). Median number of IL-6R blockade was 12 (range, 1–35), and 16 patients (76%) were concomitantly receiving corticosteroids of median dose of 10 mg (range, 5–20 mg). Of the 21 patients, irAEs improved in 14 (67%) (95% CI: 46%-87%). Of 13 evaluable patients with arthritis, 11 (85%) achieved remission or minimal disease activity as defined by the clinical disease activity index. Median time from initiation of IL-6R blockade till improvement of irAEs was 2.9 months (range, 1.5–36.9). Nineteen patients tolerated well IL-6R blockade, while two patients stopped treatment due to abdominal pain and sinus tachycardia. The median CRP levels at irAEs was 84 mg/L (0.6–187) and decreased to 1.9 mg/L (0.56–12) at 10 weeks after initiation of IL-6R blockade (P=0.02). Of the 17 evaluable patients, the overall tumor response rate by RECIST-1.1 criteria was similar before and after IL-6R blockade initiation (41% vs. 53%).ConclusionsOur data demonstrated that IL-6R blockade could be an effective therapy for irAEs management without dampening the efficacy of ICIs. Prospective clinical trials with longitudinal blood, tumor, and inflamed tissue biopsies are planned to accurately validate these findings and better study the immunobiology of irAEs.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition’s Ethics Board, approval number PA19-0089

scholarly journals POS0675 THE COMPARATIVE 3-YEAR RETENTION RATE OF TARGETED-SYNTHETIC AND BIOLOGIC DRUGS FOR RHEUMATOID ARTHRITIS: REAL-LIFE DATA FROM THE ITALIAN GISEA REGISTRY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 582.1-582
Author(s):  
E. G. Favalli ◽  
F. Iannone ◽  
E. Gremese ◽  
R. Gorla ◽  
R. Foti ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Retention Rate ◽  
Large Population ◽  
Real Life ◽  
Mechanisms Of Action ◽  
Biologic Drugs ◽  
Real Life Setting ◽  
Study Population ◽  
Targeted Drug

Background:Long-term observational data on the real-life use of JAK inhibitors (JAKis) for rheumatoid arthritis (RA) and their comparison with biological drugs are still very limited. Large population-based registries have been increasingly used to investigate the performance of targeted drugs in a real-life setting.Objectives:The aim of this study is to evaluate and compare the 3-year retention rate of JAKis, TNF inhibitors (TNFis) and biologic drugs with other mechanisms of action (OMAs) in the large cohort of RA patients included in the Italian national GISEA registry.Methods:Data of all RA patients treated with targeted synthetic or biologic drugs were prospectively collected in the Italian multicentric GISEA registry. The analysis was limited to patients who started a first- or second-line targeted drug in the period after the first JAKi was marketed in Italy (1st December 2017). The 3-year retention rate was calculated by the Kaplan-Meier method and compared between different drug classes by a log-rank test. A descriptive analysis of reasons for discontinuation was performed.Results:The study population included 1027 RA patients (79.8% females, mean age [±SD] 56.9 [±13.5] years, mean disease duration 9.8 [±9] years, mean baseline SDAI 17.5 [±11.9], ACPA positive 67.4%, RF positive 62.7%) who received JAKis (baricitinib or tofacitinib, n=297), TNFis (n=365), or OMAs (n=365) as first or second targeted drug. Main baseline characteristics of study population were overall well balanced between treatment groups. Retention rate was numerically but not statistically higher (p=0.18) in patients treated with JAKis compared with TNFis or OMAs (80.6, 78.9 and 76.4% at 1 year and 73, 56.8 and 63.8% at 3 years, respectively) (Figure 1). Drug survival was significantly higher in patients receiving concomitant methotrexate (MTX) compared with monotherapy only in TNFis (66.8 vs 47.1%, p=0.04) but not in JAKis (76.1 vs 70.1%, p=0.54) and OMAs (66.1 vs 61.9%, p=0.41) group. Therapy was discontinued in a total of 211 patients because of ineffectiveness (n=107), adverse events (n=88), or compliance/other reasons (n=16). The most frequent reason for treatment withdrawal was ineffectiveness in both JAKis (n=30 out of 56) and TNFis (n=45 out of 74) groups, whereas OMAs were discontinued more frequently because of adverse events (n=41 out of 81).Conclusion:Our data confirmed in a real-life setting a favorable 3-year retention rate of all available targeted mechanisms of action for RA therapy. As expected, concomitant MTX significantly impacted persistence on therapy of TNFis only. Discontinuations of JAKis for adverse events were infrequent overall, confirming the safety profile observed in randomized clinical trials.Figure 1.Three-year retention rate by treatment groupDisclosure of Interests:None declared

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