Efficacy and Safety of Eltrombopag with or without Immunosuppressant in Patients with Relapsed/Refractory Acquired Aplastic Anemia: A Real-World Experience

Abstract Background: Eltrombopag (EPAG) with or without immunosuppressant (IST) has been applied in acquired aplastic anemia (AA), yet data of EPAG+IST in relapsed/refractory AA was limited, and no study has compared efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients. Aims: To evaluate and compare the efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients in a real-world setting. Methods: Data from patients diagnosed as acquired AA in our center were retrospectively collected. All the enrolled patients were refractory/relapsed to the standard IST for at least 6 months before EPAG. All patients had been treated with EPAG, which was started at 25 mg/day and increased every 2 weeks to a maximum of 150 mg/day until a best response was achieved. Meanwhile, some patients were treated with cyclosporin A (CsA) or tacrolimus (FK506) at the same time. EPAG had to be prescribed for at least 6 months before evaluation. Complete response (CR), overall response (OR) and relapse rate, as well as adverse events and factors which could affect efficacy were analyzed. Results: Totally 99 patients (83 non-severe AA (NSAA) and 16 SAA) were included in the study. The median age at EPAG initiation was 46 (13-88) years old, the median time of EPAG treatment was 11 (6-41) months and the median time of follow-up was 18 (6-41) months. 72 patients were treated with EPAG+IST, including 41 (56.9%) treated with EPAG+FK506 and 31 (43.1%) treated with EPAG+CsA. 27 patients were treated with EPAG alone. No significant difference was found between EPAG+IST group and EPAG group in patient baseline characteristics like age, male proportion, NSAA proportion, presence of PNH clone, proportion of previous ATG+CsA / CsA treatment, previous IST duration and dosage. With compatible follow-up time, EPAG exposure duration and dosage, there was no significant difference in OR/CR rate at 3 rd/6 th/12 th month between patients who was treated with EPAG+FK506 and EPAG+CsA. Under similar compatible baseline conditions, the OR rate was 33.3% vs 22.2% (P=0.284) at 3 rd month, 61.1% vs 37.0% (P=0.032) at 6 th month, and 67.2% vs 42.1% (P=0.051) at 12 th month for patients treated with EPAG+IST and EPAG alone, respectively, but no significant difference was found in time to response (3 (1-12) vs 3 (1-7) months, P=0.679) or CR rate at 3 rd/6 th/12 th month (6.9%/12.5%/20.7% vs 3.7%/7.4%/5.3%, P>0.05) between the two groups. Relapse occurred at 6 th to 12 th month of EPAG treatment, and the relapse rate at 12 th month was 9.8% and 27.3% (P=0.154) for patients treated with EPAG+IST and EPAG alone, respectively. For patients treated with EPAG+IST, responders had a significantly higher baseline reticulocyte count (60.25 (11.5-230.5)×10 9/L vs 16.7 (6.6-56.6)×10 9/L, P=0.040) compared with non-responders. No predictive factors for the overall response were found for patients treated with EPAG alone. Adverse events which led to dosage regulation were gastrointestinal disorders (2.8% vs 3.7%, P=1.000), elevated creatinine (2.8% vs 0, P=0.599), elevated ALT (1.4% vs 0, P=1.000) and arthralgia (0 vs 3.7%, P=0.280) for patients with EPAG+IST and EPAG, respectively. No deaths were found in either group, while the clone evolution rate was 2.8% and 3.7% (P=1.000) in EPAG+IST and EPAG monotherapy group, respectively. Conclusion: EPAG+IST had higher OR rate than EPAG monotherapy with similar side effects for patients with relapsed/refractory acquired AA. Those with higher baseline reticulocyte count were more likely to respond to EPAG+IST. Key words: relapsed/refractory, aplastic anemia, eltrombopag, immunosuppressant, efficacy Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: In the presented study, eltrombopag was prescribed in relapsed/refractory aplastic anemia patients.

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Efficacy and Safety of the TCM Qi-Supplementing Therapy in Patients with Myasthenia Gravis: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/6512572 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Xi-qian Yang ◽

Ling Liu ◽

Wen-yu Yang ◽

Huan-huan Dong ◽

Yi-ran Yang ◽

...

Keyword(s):

Adverse Events ◽

Myasthenia Gravis ◽

Relapse Rate ◽

Response Rate ◽

Meta Analysis ◽

Effective Rate ◽

Efficacy And Safety ◽

Total Response ◽

Total Response Rate

Background. The Traditional Chinese Medicine (TCM) Qi-supplementing therapy has been used widely for treating myasthenia gravis (MG) in China. The purpose of this meta-analysis was to evaluate the efficacy and safety of Qi-supplementing therapy as an adjunctive therapy in MG patients. Methods. Seven electronic databases were searched through June 2016. Randomized controlled trials (RCTs) evaluating the add-on effect of Qi-supplementing therapy in MG patients were included. The outcome measures were the total effective rate, relapse rate, and adverse events. Results. Twenty-three RCTs involving 1,691 MG patients were included. The included studies were of low-to-moderate quality. Meta-analysis showed that Qi-supplementing therapy combined with Western medicine (WM) significantly improved the total response rate and reduced the relapse risk during 6–24 months of follow-up. Subgroup analysis showed that Qi-supplementing therapy only affected the total response rate within the first 6 months of treatment. Moreover, the rate of adverse events was lower with the addition of Qi-supplementing therapy to WM than with WM only. Conclusions. Short-term Qi-supplementing therapy combined with WM appears to be superior to WM for improving the total response rate and reducing the relapse rate. However, more high-quality RCTs are warranted owing to methodological flaws of previous trials.

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P377 Inadequate response with advanced therapies in real-world patients with Ulcerative Colitis – Results of a German claims database study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.501 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S392-S392

Author(s):

B Bokemeyer ◽

N Picker ◽

T Wilke ◽

L Rosin ◽

H Patel

Keyword(s):

Ulcerative Colitis ◽

Median Time ◽

Real World ◽

Index Date ◽

Sickness Fund ◽

Inadequate Response ◽

Advanced Therapy ◽

Advanced Therapies ◽

Significant Difference

Abstract Background Therapeutic management of Ulcerative Colitis (UC) is challenging, and clinicians are often obliged to attempt a variety of therapies in sequence until an adequate clinical response is achieved. However, real-world data regarding response rates in UC treatment are rare, particularly for later lines of therapy. Thus, this study aimed to investigate the incidence of inadequate response to advanced therapies in patients with UC. Methods This retrospective study was based on claims data from a regional German sickness fund covering the period from 01/2014-06/2019. Patients were included if they had at least two outpatient diagnoses in two different quarters or one inpatient diagnosis of UC (ICD-10: K51) and started a newly introduced advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) in 01/2015-06/2019. Patients were followed from treatment initiation (index date) until the end of the study period or loss to follow-up (median = 23.4 months). Proxies of inadequate response included: discontinuation (a supply gap of >60 days), switch, escalation (as dose increase exceeding 1.5 times the recommended maintenance dose), augmentation with 5-ASA, corticosteroid (CS) dependency (two CS prescriptions were observed starting more than 14 weeks after the index date), UC-related hospitalization, or UC-related surgery. CS dependency and treatment escalation were only assessed in the maintenance phase. Inadequate response in the analyzed sample was evaluated by means of Kaplan-Meier survival analysis. Results Among 574 UC patients (median age: 39 years; female: 53.5%), in whom an advanced therapy was initiated, 458 (79.8%) received an anti-TNF therapy, 113 (19.7%) vedolizumab and 3 (0.5%) tofacitinib. According to the available baseline period, 72 (12.4%) patients were identified as biologic-experienced. Most patients received CS (86.4%) and/or 5-aminosalicylic acids (81.7%) in the 12-month pre-index period. The median time to inadequate response to the initiated advanced therapy was 4.8 months (IQR: 2.6-11.9; Figure 1) with an inadequate response over 12 months in 75% (Figure 2). There was no significant difference in median time to inadequate response between biologic-naïve and biologic-experienced patients (4.9 vs. 4.7 months; p-value = 0.285). During the observable follow-up period, 172 (61%) patients switched from their index agent to another advanced therapy. Conclusion From the real-world settings in Germany, we found an inadequate response in UC-patients starting an advanced therapy in 75% of patients over 12 months. There is a need for more effective therapies among these patients.

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Real-World Effectiveness and Safety of Eltrombopag in Patients with Aplastic Anemia: A Chinese Nationwide Survey

Blood ◽

10.1182/blood-2019-126441 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5020-5020

Author(s):

Wenrui Yang ◽

Bing Han ◽

Hong Chang ◽

Bingyi Wu ◽

Fankai Meng ◽

...

Keyword(s):

Aplastic Anemia ◽

Real World ◽

Overall Response Rate ◽

Response Rate ◽

Line Treatment ◽

First Line ◽

Overall Response ◽

Treatment Naïve ◽

First Line Treatment

Immunosuppressive therapy (IST) based on antithymoglobin (ATG) and cyclosporin (CsA) is the first-line treatment for severe aplastic anemia (SAA) patients who are unfit for transplantation,and the overall response rate (ORR) is about 70%.The utility of eltrombopag (EPAG),a TPO receptor agonist, achieved robust hematologic response in refractory and treatment-naïve SAA patients in clinical trials and some other studies. However, only a few data came from Asia countries where higher incidence of AA has been reported. A retrospective study on the use of EPAG in AA was conducted in mainland China. Aplastic anemia (transfusion dependent non-severe, severe, and very severe) patients who started eltrombopag before Feb 2019 and continued for at least 3 months either as first-line treatment or as rescue treatment, were enrolled. The maximum daily dosage of EPAG used continuously for at least 2 weeks is defined as the stable dosage. Response criteria were referred to that used in previous reports (Townsley DM, NEJM 2017; BCSH, BJH 2016). Fifty-six patients from eleven centers were enrolled in this study, including 26 males and 30 females at the median age of 39 (7-80) years. All patients were transfusion-dependent by the time of EPAG administration, and there were 14 VSAA, 24 SAA and 18 transfusion dependent non-severe aplastic anemia (TD-NSAA). Nineteen treatment-naïve patients received EPAG and IST (ATG+CsA, n=10; CsA/CsA+androgen, n=9) as first-line treatment. Thirty-seven patients were refractory to IST. Eltrombopag was administered at a median dose of 75 (25-150) mg per day for 7 (3-31) month. The median follow-up time was 9 (3-40) months. The overall response rate in patients receiving EPAG as first-line therapy was 78.9% (15/19), and most patients achieved complete response (CR) (10/15). Among the 10 patients receiving ATG+CsA, 6 patients achieved hematologic response (HR) at 3 months post-treatment, including 3 CR. Six patients were diagnosed as VSAA and three achieved HR. For the 9 patients treated with CsA/CsA+androgen, 8 achieved HR (88.9%) and 4 were CR (44.4%) at 3 months. By last follow-up, the cumulative HR rate was 70% in ATG+CsA group and 89% in CsA/CsA+ androgen group. Among the 14 responders, 11 patients receiving EPAG at a stable dosage ≤75mg/d and achieved HR at 3 months. The overall response rate in IST-refractory patients was 46% (17/37), with trilineage response in 27% patients at 3 months. For the 18 ATG+CsA refractory SAA patients,trilineage HR occurred in 4 patients (22.2%, 4/18), bi-lineage HR in one patient and single lineage HR in one patient. Thus, the total HR was 33.3% (6/18) at 3 months and increased to 44% (8/18) by last follow-up. Among the 19 CsA/CsA+ androgen refractory patients, 6 (31.5%, 6/19) achieved trilineage HR, one achieved bi-lineage HR and 4 achieved single lineage response. Total HR rate was 57.9% (11/19) at 3 months after EPAG initiation and 68% (13/19) by last follow-up, including 9 patients with trilineage HR. Among 17 responders, 13 received a stable EPAG dose of≤75mg/d. Most patients tolerated EPAG well. Adverse events occurred in 29 patients (52%) and most were mild to moderate, including gastrointestinal symptom (n=15, e.g. abdominal pain, nausea), impaired liver function (n=5), skin changes (n=7, e.g. skin pruritus and rash) and musculoskeletal pain (n=6), and venous thrombus (n=2). Eltrombopag dosage was reduced in 2 patients due to severe digestive symptoms at 100 mg/d and discontinued in one patient who suffered from upper limb venous thrombus. In conclusion, EPAG is effective and safe in treating Chinese AA patients at a daily dose of 75mg and less. The real-world result of EPAG in Chinese patients is similar to those reported in Western countries. Disclosures No relevant conflicts of interest to declare.

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PERsistent Sitagliptin treatment & Outcomes (PERS&O 2.0) study, long-term results: a real-world observation on DPP4-inhibitor effectiveness

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001507 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001507

Author(s):

Antonio Carlo Bossi ◽

Valentina De Mori ◽

Carlotta Galeone ◽

Davide Pietro Bertola ◽

Margherita Gaiti ◽

...

Keyword(s):

Adverse Events ◽

Real World ◽

Repeated Measures ◽

Long Term Results ◽

Italian Population ◽

Drug Survival ◽

Kaplan Meier ◽

Significant Difference

IntroductionSitagliptin is a dipeptidyl peptidase 4 inhibitor for the treatment of type 2 diabetes (T2D). Limited real-world data on its effectiveness and safety are available from an Italian population.Research design and methodsWe evaluated long-term clinical data from the single-arm PERsistent Sitagliptin Treatment & Outcomes (PERS&O) study, which collected information on 440 patients with TD2 (275 men, 165 women; mean age 64.1 years; disease median duration: 12 years) treated with sitagliptin ‘add-on’. For each patient, we estimated the 10-year cardiovascular (CV) risk using the UK Prospective Diabetes Study (UKPDS) Risk Engine (RE). Drug survival was evaluated using Kaplan-Meier survival curves; repeated measures mixed effects models were used to evaluate the evolution of glycated hemoglobin (HbA1c) and CV risk during sitagliptin treatment.ResultsAt baseline, most patients were overweight or obese (median body mass index (BMI) (kg/m2) 30.2); median HbA1c was 8.4%; median fasting plasma glucose: 172 mg/dL; median UKPDS RE score: 24.8%, being higher in men (median 30.2%) than in women (median 17.0%) as expected. Median follow-up from starting sitagliptin treatment was 5.6 years. From Kaplan-Meier curves, the estimated median drug survival was 32.8 months when considering discontinuation for any cause and 58.4 months when considering discontinuation for loss of efficacy. A significant improvement in HbA1c was evident during treatment with sitagliptin (p<0.01): the reduction was rapid (median HbA1c after 4–6 months: 7.5%) and continued at longer follow-up. When comparing patients treated with sitagliptin versus those stopping sitagliptin and switching to another antihyperglycemic drug, we detected a significant difference in the evolution of HbA1c in favor of patients who continued sitagliptin treatment. The UKPDS RE score at 10 years and the BMI significantly improved during treatment with sitagliptin (p<0.001). Adverse events were relatively uncommon.ConclusionPatients with T2D treated with sitagliptin achieved an improvement in metabolic control and a reduction in CV risk and did not experience relevant adverse events.

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Efficacy and Safety of Ponatinib in CML and Ph+ ALL Patients in Real-World Clinical Practice: Data from a Belgian Registry

Blood ◽

10.1182/blood-2018-99-114070 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1744-1744 ◽

Cited By ~ 1

Author(s):

Timothy Devos ◽

Koen Theunissen ◽

Fleur Samantha Benghiat ◽

Alain Gadisseur ◽

Stef Meers ◽

...

Keyword(s):

Clinical Practice ◽

Median Time ◽

Real World ◽

Research Funding ◽

Safety Data ◽

Efficacy And Safety ◽

Best Response ◽

History Of ◽

T315i Mutation

Abstract Background Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for adult patients with resistant or intolerant chronic phase (CP), accelerated phase, or blast phase chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), or those with the T315I mutation. In Belgium, ponatinib has been commercially available since March 2016. The goal of this registry was to collect efficacy and safety data in CML and Ph+ ALL patients and to evaluate ponatinib in routine clinical practice in Belgium. Methods This ongoing, prospective, multi-center registry includes patients ≥18 years of age with CML or Ph+ ALL, who have initiated ponatinib treatment. Demographic, efficacy and safety data were collected for patients enrolled from March 2016 (day 0) onwards. Results up to study month 24 are presented. Data were analyzed by descriptive statistics. Ethics Committee approval was obtained and all patients provided informed consent. Results At time of data analysis, 34 patients (21 CP-CML and 13 Ph+ ALL) were enrolled. The median age of CP-CML and Ph+ ALL patients was 57 and 55 years, respectively. Patients were heavily pretreated: 90% of CML and 92% of Ph+ ALL patients had received ≥2 prior TKIs. Several patients had one or more risk factors for TKI cardiovascular toxicity: hypertension (10), history of cardiovascular disease (11), smoker (10), hypercholesterolemia (5), and diabetes (4). Median follow-up was 539 days for CML and 135 days for Ph+ ALL patients. The reasons for starting ponatinib therapy were related to refractoriness to previous TKIs (36%), progression (18%), presence of the T315I mutation (18%) or intolerance (29%). Eighty percent (8/10) of the patients who started ponatinib due to intolerance to previous TKIs had received ≥3 prior TKIs. At entry, 17 of the 34 patients (50%) had a confirmed BCR-ABL mutation. Of these 17, 10 (59%; 5 CML and 5 Ph+ ALL) had the T315I mutation. Starting doses of ponatinib in CML patients were 45 mg (76%), 30 mg (10%) and 15 mg (14%) once daily. Starting doses in Ph+ ALL patients were 45 mg (85%), 30 mg (8%) and 15 mg (8%). At latest follow up, the median treatment duration for the 21 CML patients was 531 days (range 15 - 2483) and for the 13 Ph+ ALL patients it was 123 days (range 13 - 1945). Best response was a major molecular response (MMR), which was obtained in 71% of CML patients and 38% of Ph+ ALL patients. The median time-to-best response was 175 days in CML and 35 days in Ph+ ALL patients. In the 10 patients (7 CML and 3 Ph+ ALL) who started ponatinib because of intolerance to several previous TKIs, 80% achieved MMR. The median time to achieve best response in these patients was 192 days for CML and 31 days for Ph+ ALL patients. Treatment-related adverse events (AEs) were reported in 20 patients (59%); the most common were rash (26%), dry skin (9%) and constipation (9%). Three patients reported ≥1 treatment-related serious AE (SAE): thrombocytopenia (n=1), cholecystitis (n=1) and hepatocellular injury (n=1). Three serious cardiovascular events were observed in 1 patient, who had a history of congenital cardiomyopathy and aortic prosthesis. They were scored as not related to ponatinib. Dose reductions or interruptions occurred in 33 cases (20 in CML and 13 in Ph+ ALL patients), with the following reasons most frequently mentioned: AEs (76%), to prevent AEs (18%) and other (6%). Dose increases occurred in 12 cases (10 in CML and 2 in Ph+ ALL patients), for the following reasons: good tolerance of treatment (58%), no or low response (33%) or other (8%). At time of analysis, 19 patients (9 CML and 10 Ph+ ALL) had discontinued treatment, of which 32% due to AEs, 5% due to an SAE, 21% due to planned allogeneic transplant, 16% due to disease progression and 26% due to other reasons. [Note: Percentages may not total 100 due to rounding] Conclusion Real-world evidence from this Belgian registry shows that ponatinib has a favorable efficacy and safety profile in, and supports its use in CML and Ph+ ALL patients who are resistant or intolerant to previous therapies or those with the T315I mutation. Deep molecular responses were obtained in the majority of patients. No new safety signals emerged with ponatinib treatment than those previously reported. Funding: Incyte Biosciences Benelux BV Disclosures Devos: Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Theunissen:Incyte: Honoraria. Van Eygen:Janssen: Consultancy, Research Funding; Roche: Research Funding; Amgen: Research Funding. Kuipers:Incyte Biosciences Benelux BV: Employment.

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Up-Front Treatment of Diffuse Large-B Cell Lymphoma (DLBCL) in Elderly Patients with Rituximab in Combination with CHOP-Like Chemotherapy: A Multicenter Study on the Current Clinical Management.

Blood ◽

10.1182/blood.v106.11.4778.4778 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4778-4778 ◽

Cited By ~ 1

Author(s):

Miguel A. Canales ◽

Javier de la Serna ◽

Pilar Sabin ◽

Joaquin Diaz-Mediavilla ◽

Mariano Provencio ◽

...

Keyword(s):

Overall Survival ◽

Clinical Practice ◽

Adverse Events ◽

Elderly Patients ◽

Overall Response Rate ◽

Response Rate ◽

B Cell Lymphoma ◽

Overall Response ◽

Significant Difference

Abstract Based on results of GELA study, rituximab in combination with CHOP chemotherapy, given for eight cycles, may be considered the new standard of care for patients older than 60 years diagnosed with DLBCL. However, the afraid of early toxicity and underlying co-morbid illness in elderly patients implies often adjustments in this scheme. The aim of this study was to analyze the routine clinical practice in the up-front treatment of elderly patients (>65 years) with DLBCL. We have enrolled onto this study 80 patients (48 females) with median age 74 years (range, 65 to 85 years) who have been treated with CHOP-like regimens in combination with rituximab as first-line therapy. The 75% of patients had ECOG 0-1, 81% had Ann-Arbor stage III-IV, 41% had B-symptoms, 59% had aIPI 2-3, 39% had bulky disease (> 7 cm) and 55% had elevated beta-2 microglobulin. The most of patients received as up-front therapy R-CHOP (89%); R-CNOP and R-CEOP (doxorubicin is substituted for mitoxantrone and epirubicin, respectively) were the alternative regimens administered. The 57.5% of patients received 6 courses of treatment; the 25% received less than 6 cycles and only the 6% of patients (5 out of 80 patients) received 8 courses of treatment. In 31 out of 80 patients the doses of chemotherapy was reduced; in 20 patients the doses of chemotherapy were reduced in all courses and 2 patients received reduced doses of chemotherapy in 5 out of 6 cycles. In the 40% of patients G-CSF have been administered. The overall response rate was 86% (72% CR/CRu, 14% PR). In the 22 patients who received the lower doses of chemotherapy the overall response rate was 82% (50% CR/CRu) versus 88% in the remaining patients (81% CR/CRu) (p<0.05). Adverse events were observed in the 47.5% of patients and neutropenia was the most frequent complication. In those patients who received reduced doses of chemotherapy less adverse events were observed (13.6% versus 60.3%, p<0.001). With a median follow-up of 15 months, the event-free survival in the assessable population has not been reached (60% at 2 years) and there was no significant difference in those patients who have received the reduced doses of chemotherapy (median 18.5 months versus not reached). The median overall survival has not been reached. At 2 years overall survival is 73% in the entire population and 51% in patients receiving the reduced doses of chemotherapy compared to 80% in the remaining patients but the difference was not statistically significant. In conclusion, in our current clinical practice, 6 courses of chemotherapy (CHOP-like) in combination with rituximab is the commonest regimen used for the treatment of elderly patients. The administration of reduced doses of chemotherapy is associated with both a significant decrease in adverse events and complete response rates and may be translated into a shorter event-free and overall survival. A longer follow-up may be necessary to reveal this difference. Logically, randomized trials are mandatory to address differences between 6 and 8 courses of immunochemotherapy in this population.

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Real-world experience of talimogene laherparepvec in patients receiving immunotherapy in metastatic melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e22003 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e22003-e22003

Author(s):

Tapas Ranjan Behera ◽

Jung Min Song ◽

Jennifer S. Ko ◽

Michael J. McNamara ◽

Pauline Funchain ◽

...

Keyword(s):

Clinical Trials ◽

Metastatic Melanoma ◽

Treatment Response ◽

Median Time ◽

Real World ◽

Overall Response Rate ◽

Response Rate ◽

Talimogene Laherparepvec ◽

Overall Response

e22003 Background: Talimogene laherparepvec (TVEC) is an oncolytic herpes virus approved by the FDA for intralesional therapy in unresectable metastatic melanoma. However, little is known regarding the effectiveness of TVEC+checkpoint inhibition (CPI) outside of clinical trials. We present outcomes of the largest single institution experience with TVEC in the context of different immune checkpoint inhibitors. Methods: All patients with stage III-IV unresectable melanoma having received TVEC were evaluated. Patient demographics, clinicopathological characteristics, TVEC treatment response and outcomes were assessed. Final analysis included those who received TVEC adjacent to CPI with a minimum 6-month follow-up, excluding patients on clinical trials. Response was estimated by sequential measurement of injectable on-target lesions. Results: A total of 62 patients received TVEC from 2016 to 2019, of which 43 remained excluding Merkel cell carcinoma, patients on trials, and TVEC monotherapy. Of 30 patients with available treatment response data and at least 6-months follow-up, median age was 68.5 years (30-99 years), 40% were female, 16 (53.3%) stage IV. Median follow-up was 17.5 months (6-43 months). At 6 months, 20 (67.7%) patients were alive; at 1 year, 17 (56.7%) patients were alive. Eighteen patients received pembrolizumab, 7 nivolumab and 5 ipilimumab/nivolumab. Median number of TVEC doses received was 8 (3-31 doses). Median time on TVEC therapy was 4 months (1-26 months). Overall response rate for on-target lesions was 24 (80%), with complete local response (CR) in 15 (50%), partial response (PR) in 9 (30%), and progressive disease (PD) in 6 (20%). Median time to response was 6 weeks (2-17 weeks); 5 in CR, 6.5 in PR and 5.5 in PD groups. Adverse events were mostly mild and limited to constitutional symptoms. Conclusions: To our knowledge this is the largest real-world experience assessing TVEC in patients receiving CPI. Local overall response rate appears higher in comparison to historic numbers for TVEC monotherapy. The findings demonstrate that TVEC is an effective and safe treatment for metastatic melanoma and has robust outcomes in real-life clinical settings.

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Retrospective Study of the Efficacy and Safety of Treatment with Subcutaneous Injection of Bortezomib in De Novo Patients with MM

Blood ◽

10.1182/blood.v126.23.5074.5074 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5074-5074

Author(s):

Chengcheng Fu ◽

Ling Ma ◽

Shuang Yan ◽

Hui Liu ◽

Yun Xu ◽

...

Keyword(s):

Adverse Events ◽

Subcutaneous Injection ◽

De Novo ◽

Conflicts Of Interest ◽

Risk Group ◽

Induction Treatment ◽

Efficacy And Safety ◽

The Poor ◽

Significant Difference

Abstract [Objective] The induction therapy of multiple myeloma (MM) has dramatically changed due to the availability of new drugs such as bortezomib.To explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo MM patients, a total of 56 patients treated with PAD form June 2008 to January 2015 were retrospective analyzed. [Methods] 29 patients in PAD group received intravenous injection of bortezomib 1.3mg/m2, d1,4,8,11, Adr iv 40mg/m2, d1, Dex iv 20mg, d1,2,4,5,8,9,11,12; another 28 in improved PAD group received subcutaneous injection of bortezomib1.3mg/m2, d1,4,8,11, Adr iv 40mg/m2, d1, Dex iv 20mg, d1,2,4,5,8,9,11,12. The efficacy and safety of two groups were analyzed. [Results] The response rate >= VGPR after 4 cycles of PAD or improved PAD were 51.7% and 51.9% respectively.With a median follow up of 24 months,the median TTP , PFS and OS of the PAD group was 47 months, 42 months, 63 months respectively, but the time of the improved PAD group wasn't shown up yet.In the improved PAD group,2y- TTP ,PFS and OS was 94.4%, 94.4%, 100%. With a follow-up to 60 months,the OS of standard-risk group[without FISH 1q21+, or t(4;14), or p53-]was 61.9%,but the survival was only 31.9% in FISH high-risk group. OS, PFS of the patients with 1q21 amplification was 18.7-56.4 months and 9.7-53.5 months, showed statistical difference (P=0.029), (P=0.037), compared to FISH negative patients,which was 51.5-71.3 months and 39.4-68.4 months. The study found that the hemoglobin < 100 g/L or 1q21+ were the poor prognosis factors for patients' OS, while subcutaneous injection of bortezomib could improve OS(P=0.042), mainly because compared to PAD group,Grade 3 or worse adverse events were significantly reduced in improved PAD group. the most common were peripheral neuropathy (P=0.049), infection(0.004). When α=0.1, leukopenia(P=0.086), diarrhea(P=0.093) also showed statistically significant difference. [Conclusions] The improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had greatly improved the OS.1q21 amplification was the poor prognostic factors in PAD induction treatment of MM. Disclosures No relevant conflicts of interest to declare.

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Three-year real-world outcomes of intravitreal anti-VEGF therapies in patients affected by myopic choroidal neovascularization

European Journal of Ophthalmology ◽

10.1177/1120672120963455 ◽

2020 ◽

pp. 112067212096345

Author(s):

Paolo Corazza ◽

Jamil Kabbani ◽

Taha Soomro ◽

Mostafa Mohamed Ragheb Alam ◽

Francesco Maria D’Alterio ◽

...

Keyword(s):

Adverse Events ◽

Choroidal Neovascularization ◽

Real World ◽

Adverse Event Rate ◽

Real World Data ◽

Serious Adverse Events ◽

Myopic Choroidal Neovascularization ◽

Anti Vegf ◽

Significant Difference

Purpose: To describe real world data in patients affected by myopic choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factors (VEGFs) and to compare our results with previous studies and clinical trials. Methods: This retrospective monocentric cohort study analyzed 96 eyes of 96 myopic-CNV patients treated with an anti-VEGF pro-re-nata regimen over a 3-year-long follow up period. Aflibercept and Ranibizumab were considered as first-line agents whereas Bevacizumab was reserved on a compassionate basis in patients outside the criteria for treatment. All patients underwent a best-corrected visual acuity (BCVA) recording at each follow up visit. Results: Our data showed that all three molecules produced significant improvements in BCVA at year 1, with no significant differences between the three drugs. Moreover, during the second year of treatment, Ranibizumab and Bevacizumab showed a significant improvement in the visual function. However, at year 3 of treatment, the data available indicated the BCVA improvement was not significant with Ranibizumab and Bevacizumab. In addition, no significant difference in the average number of injections between the three groups was detected over the follow up period. No serious adverse events were recorded, but five minor adverse events documented. Conclusion: Our study correlates with previous studies showing significant BCVA gains with the use of these molecules. Similarly, all three molecules seem to provide a similar duration of effects as previous studies have shown, with a low ocular adverse event rate.

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Efficacy and Safety of Non-Steroidal Anti-Androgens in Patients with Metastatic Prostate Cancer: Meta-Analysis of Randomized Controlled Trials

Reviews on Recent Clinical Trials ◽

10.2174/1574887114666191105152404 ◽

2020 ◽

Vol 15 (1) ◽

pp. 34-47 ◽

Cited By ~ 1

Author(s):

Muhammed Rashid ◽

Madhan Ramesh ◽

K. Shamshavali ◽

Amit Dang ◽

Himanshu Patel ◽

...

Keyword(s):

Prostate Cancer ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Quality Assessment ◽

Cochrane Library ◽

Control Group ◽

Controlled Trials ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Significant Difference

Background: Prostate cancer (PCa) is the sixth primary cause of cancer death. However, conflicts are present about the efficacy and safety of Non-steroidal anti-androgens (NSAA) for its treatment. The aim of this study was to assess the efficacy and safety of NSAAs versus any comparator for the treatment of advanced or metastatic PCa (mPCa). Methodology: MEDLINE and the Cochrane Library were searched. References of included studies and clinicaltrials.gov were also searched for relevant studies. Only English language studies after 1990 were considered for review. Randomized controlled trials (RCTs) examining the efficacy and safety of NSAAs as compared with any other comparator including surgery or chemotherapy in mPCa patients were included. The outcomes include efficacy, safety and the tolerability of the treatment. The Cochrane Risk of Bias Assessment Tool was used for quality assessment. Two authors were independently involved in the selection, extraction and quality assessment of included studies and disagreements were resolved by discussion or by consulting a third reviewer. Results: Fifty-eight out of 1307 non-duplicate RCTs with 29154 patients were considered for the review. NSAA showed significantly better progression-free survival [PFS] (Hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.78; P=0.0001), time to distant metastasis or death [TTD] (HR, 0.80; 95% CI 0.73-0.91; p<0.0001), objective response (Odds ratio [OR], 1.64; 95% CI 1.06-2.54; P=0.03) and clinical benefits (OR, 1.33; 95% CI 1.08-1.63; P=0.006) as compared to the control group. There was no significant difference observed between the groups in terms of overall survival (HR, 0.95; 95%CI, 0.87-1.03; P=0.18) and time to progression (HR, 0.93; 95% CI 0.77-1.11; P=0.43). Treatment-related adverse events were more with the NSAA group, but the discontinuation due to lack of efficacy reason was 43% significantly lesser than the control group in patients with mPCa. Rest of the outcomes were appeared to be non-significant. Conclusion: Treatment with NSAA was appeared to be better efficacious with respect to PFS, TTD, and response rate with considerable adverse events when compared to the control group in patients with metastatic PCa.

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