Treatment outcome of immune thrombocytopenia

2012 ◽  
Vol 153 (41) ◽  
pp. 1613-1621
Author(s):  
János László Iványi ◽  
Éva Marton ◽  
Márk Plander
Keyword(s):  
Immune Thrombocytopenia ◽  
Disease Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Median Disease Free Survival ◽  
Novel Drugs ◽  
Disease Free ◽  
First Line Treatment

Introduction: Treatment of immune thrombocytopenia is sometimes difficult and needs personal setting. According to evidence-based guidelines, corticosteroids are suggested for first-line treatment. In case of corticosteroid ineffectiveness, second-line therapeutic options (splenectomy, immunosuppressive drugs and, recently, thrombopoietin-mimetics) may result in beneficial therapeutic effect. Aims: The aim of the authors was to examine the clinicopathological data, disease course, treatment results, and the effectiveness of novel drugs in patients with immune thrombocytopenia. Patients and methods: The authors retrospectively analysed the files of 79 immune thrombocytopenic patients (26 males and 53 females) diagnosed and treated at the hematologic in- and outpatient units of the Markusovszky Hospital, County Vas, Hungary between January 1, 2000 and December 31, 2011. Remission rates, disease-free and overall survivals in response to corticosteroids (first-line treatment), after splenectomy (in cases when corticosteroids proved to be ineffective) and following second-line treatment were analysed. Survival curves were constructed using statistical software programs. Results: Of the 79 patients during a median follow-up of 66 months (min. 3, max. 144 months), 28 patients receiving first-line corticosteroids achieved complete remission and remained in a prolonged disease-free condition (35.4%; median disease-free survival 75.5 months; min. 2, max. 140 months). Thirty-eight patients underwent splenectomy after ineffective treatment with corticosteroids or other immunosuppressive (48.0%; median disease-free survival 94.2 months; min. 6, max. 136 months). Surgical complications occurred in 2 cases, while postoperative and late infections were absent. Five patients died but death was not related to immune thrombocytemia. Second-line treatment was applied in 13 patients (16.4%) and among these patients relapse of immune thrombocytopenia after splenectomy was observed in 6 patients. Favourable effects of both conventional (immunosuppressive) and novel treatments (rituximab, thrombopoietin-mimetics) were also detected. Conclusions: More than two-thirds of patients with immune thrombocytopenia responded to corticosteroids or to splenectomy and achieved prolonged disease-free remission. Novel drugs (rituximab, thrombopoietin-mimetics) applied only in few cases produced also favourable results in patients not responding to corticosteroids and splenectomy. Orv. Hetil., 2012, 153, 1613–1621.

scholarly journals Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

2021 ◽  
Vol 14 (2) ◽  
pp. 151
Author(s):  
Anica Högner ◽  
Peter Thuss-Patience
Keyword(s):  
Cell Death ◽  
Gastric Carcinoma ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Disease Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
The Usa ◽  
First Line Treatment

Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.

Rituximab (Mabthera) Improves the Treatment Results of DHAP-VIM-DHAP and ASCT in Relapsed/Progressive Aggressive CD20+ NHL. A Prospective Randomized HOVON Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 328-328 ◽  
Author(s):  
Edo Vellenga ◽  
Annelise Notenboom ◽  
Mars van ‘t Veer ◽  
Josée Zijlstra ◽  
Willem E. Fibbe ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Response Duration ◽  
Rank Test ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Post Transplantation ◽  
Free Survival ◽  
Significant Difference ◽  
First Line Treatment

Abstract A total of 239 patients with relapsed/progressive aggressive CD20+ NHL after/during adriamycin containing regimens, were recruited to the randomized HOVON-44 trial comparing DHAP-VIM-DHAP followed by BEAM and autologous stem cell re-infusion (ASCT)(“DHAP-arm”) with DHAP-VIM-DHAP in conjunction with Rituximab (375 mg/m2) and ASCT (“R-DHAP arm”). Of the included patients, 202 were evaluable and randomized to the DHAP arm (n=101) or R-DHAP arm (n=101). Only patients with CR/PR after two courses of intensive chemotherapy were eligible for ASCT. Patients were well balanced for risk factors. In both arms the majority of patients had not been exposed to Rituximab during first line treatment. As of July 2006, median follow-up of all patients still alive is 24.5 months. After two courses of chemotherapy PR/CR was obtained in 49 % of the patients in the DHAP arm and 77% in the R-DHAP arm (p=<.01;intention to treat analysis). Post-transplantation PR/CR was obtained in 41% and 58% of the patients respectively (p=.40). A significant difference between both arms was observed for failure free survival (FFS), disease free survival (DFS) and overall survival (OS) in favor of the Rituximab arm (p<.05, table 1). The less pronounced difference in OS between both arms is most likely due to the fact that non-responding or relapsing patients in the DHAP arm received salvage treatment with a Rituximab containing regimen. Additionally, a subgroup analysis was performed according to type of response to first-line treatment:1) Response duration more than 3 months (n=138); 2) Progression or response duration less than 3 months (n=64). Within both subgroups, the hazard ratio’s for the endpoints were of equal magnitude (.40–.60), indicating that the beneficial effect of Rituximab existed in both subgroups. In conclusion these results demonstrate that the addition of Rituximab to second line of chemotherapy followed by ASCT results in a significant improved FFS, DFS, and OS in patients with relapsed/progressive aggressive CD20+ NHL. Table 1 FFS DFS OS *: 2 years estimate DHAP-arm* 21% 46% 48% R-DHAP arm* 52% 82% 62% Hazard ratio .40 .32 .61 p-value log rank test <0.001 0.003 0.03

South Brazilian Chronic Myeloid Leukemia (CML) Profile Patients: How We Treat and Our Results

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4286-4286
Author(s):  
Laura Fogliatto ◽  
Marcelo Capra ◽  
Mariza Schaan ◽  
Mario Sergio Fernandes ◽  
Waldir Pereira ◽  
...  
Keyword(s):  
Public Health ◽  
Chronic Phase ◽  
Imatinib Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Blastic Phase ◽  
South Of Brazil ◽  
First Line Treatment

Abstract CML is a well characterized disease with a known chromosomal abnormality. The inhibition of BCR-ABL protein tyrose kinase activity represented an advance in the treatment of this disease. Imatinib is effective in chronic, accelerated and blastic phase disease, and is the CML first line treatment around the world. In Brazil, this drug is provided by the State since 2003. The drug is available for second line treatment in chronic phase and for accelerated and blastic phase as the first line therapy. In chronic phase, the patients are treated first with interferon. If this treatment is too toxic or not effective, the choice therapy is imatinib 400 mg and the dose can be escalated up 600 mg. In accelerated and blastic phases the treatment is imatinib 600 mg. Mutational studies are not routinely performed and the failing patients are encourage to participate in bone marrow transplantation programs or clinical research centers. The present data are obtained from public health hospital database and included 400 CML Ph+ patients from Rio Grande do Sul, south of Brazil. 232 patients are male and 158 female and around 70% were Caucasian. The median age at diagnosis was 46, 79 y (median 49, 28). The mean laboratory values at diagnosis were: hematocrit 33 (median 34, 8), hemoglobin 11, 08 (median 11, 40), white blood cells 158.594 (median 110.000) and platelets 466.000 (median 380.000). From the 400 patients, 300 pts were diagnosed in chronic phase, 52 pts in accelerated phase and 20 pts in blastic phase. In 28 patients the disease phase was unknown. In the majority of patients Imatinib was started because interferon treatment was not tolerated (121 patients) or ineffective (123 patients). Of these patients 285 were in chronic, 59 pts in accelerated and 17 pts in blastic phases. The cytogenetic response evaluated at 12 months of treatment was available in 231 patients: 164 complete responses, 20 major responses, 15 minor responses and 32 patients demonstrated none or minimal response to therapy. In 169 patients the response is unknown. The progression free survival for the chronic phase patients in 80 months of observation is 90% and the event free survival for the entire group is 60% in the same period. The progression from chronic to accelerated or blastic phase was more common in the first year of imatinib treatment and decreased progressively until the fifth year of therapy. This data demonstrate the epidemiologic profile and the treatment results of CML patients in south of Brazil. Imatinib is available in public health system as a second line treatment and the survival rate is quite good. Since last July this drug has been available as first line treatment, even in chronic phase. A longer follow up and a uniform database registry are needed to study the impact of imatinib treatment in this population.

Impact of first-line cisplatin versus non-cisplatin based chemotherapy on progression-free survival in patients with advanced urothelial carcinoma previously treated with perioperative cisplatin based chemotherapy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 335-335
Author(s):  
Jennifer A Locke ◽  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Andrea Necchi ◽  
Patrizia Giannatempo ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Ecog Ps ◽  
Line Chemotherapy ◽  
First Line Treatment

335 Background: Perioperative cisplatin based chemotherapy (PCBC) is a standard of care in the management of muscle invasive urothelial carcinoma (UC). Cisplatin based (C) therapy also represents the historical first line treatment of metastatic disease. There is however no data to guide the optimal choice of first line chemotherapy regimen – C re-treatment vs other second-line or non cisplatin regimens (NC) –in UC patients who relapse after receiving PCBC. This multicenter retrospective study compares C vs NC first line treatment on progression-free survival (PFS) for patients (pts) with advanced UC after PCBC and cystectomy. Methods: Data were collected for patients who received various first-line chemotherapies for advanced UC following previous PCBC therapy. Cox proportional hazards models were used to investigate the prognostic ability of type of peri-operative / first-line chemotherapy, visceral metastasis, ECOG status, time from prior chemotherapy (TFPC), anemia, leukocytosis and albumin on PFS. Results: Data were available for 145 pts from 12 centers. The mean age was 62 years, 113 (77.9%) were men and ECOG-PS was 0 or >0 in 74 (51.0%) and 61 (42.0%) patients. Ninety-one (62.8%) pts received C first line, the median number of cycles was 4 (range 1-17) and the median TFPC was 6.2 months (range 1-154). Median overall survival was 86 weeks (95% CI 70-106) and median PFS was 24 (95% CI 18-27) weeks. Time from perioperative chemotherapy (TFPC) (>52 weeks vs ≤52 weeks; HR 0.63 p=0.027) and ECOG-PS at first line (1+ vs 0; HR 1.73 p=0.010), were prognostic of PFS. No significant effect was noted for C vs NC first line (p=0.70); however, among patients with TFPC >52 weeks, patients with NC had worse PFS (median 4.6 months, 95% CI 1.8-12.2) than those who received C (median 8.1, 95% CI 3.2-16.3). Conclusions: There is no evidence to suggest overall superiority of C vs NC based first line chemotherapy or a second-line regimen in patients with advanced UC who received prior PCBC. However, those with TFPC >52 weeks should probably receive C first line chemotherapy given better PFS with C.

Non Hodgkin Lymphoma: Experience of a Referral Hospital.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4774-4774
Author(s):  
Humberto Castellanos-Sinco ◽  
Silvia Rivas-Vera ◽  
Victoria E. Ferrer Argote ◽  
Carlos Martínez-Murillo ◽  
Christian Omar Ramos Peñafiel
Keyword(s):  
Conflicts Of Interest ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Chop Regimen ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Global Trend ◽  
First Line Treatment

Abstract Abstract 4774 Introduction Non-Hodgkin lymphomas corresponds a heterogeneous group of neoplasms deriving of lymphocytes, in development countries represents a great cause of morbility and mortality. The General Hospital of Mexico is a referral centre localized in Mexico City, whose first cause of primary hematology attention in NHL. Material and methods Is an observational, descriptive and retrospective study, based on medical records of patients treated between 1992-2009. Objectives Determine the response, overall survival (OS) and event free survival (EFS) (progression, death or last visit) associated with treatment by CHOP as first line treatment without rituximab and four cycles of DEP as a second line treatment (dexamethasone 40 mg/m2 IV daily, days 1-4, VP-16 300 mg/m2 IV daily, days 1-2 and cysplatin 100 mg/m2 IV day 1), in cycles of 21 days each one. Results In a period of 17 years, 303 of 632 patients were eligible. The average age was 52 years, with male:female relation 1:1.1. Thirty four percent of the sample were older 60 years. The most frequent NHL was diffuse large B cell lymphoma (DLBCL) (N=146 treated), 60% were IPI low plus intermediate low; the most frequent indolent NHL were follicular lymphoma (N=20 treated), 71% were FLIPI low plus intermediate. The resting 94 cases were treated with CHOP, too. Conclusion The global trend is the addition of rituximab to all of CHOP-based regimens. In our country, because the economics limitations, the use of rituximab is low. The CHOP regimen remains the first line treatment; and the second line treatments are based on the experience of the institutional protocols. DEP is the institutional protocol for second line treatment and their response, OS and EFS are comparable to more expensive protocols (ESHAP, DHAP). Concluding that DEP is a low toxic and cheaper second line regimen and this could be an alternative for development countries. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Analysis of Relapse Biopsies in Classical Hodgkin Lymphoma Reveals Correlations with Outcome after Autologous Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 136-136
Author(s):  
Fong Chun Chan ◽  
Anja Mottok ◽  
Alina S. Gerrie ◽  
Maryse M. Power ◽  
Kerry J. Savage ◽  
...  
Keyword(s):  
Gene Expression ◽  
Line Treatment ◽  
Second Line ◽  
Classical Hodgkin Lymphoma ◽  
First Line ◽  
Free Survival ◽  
Gene Predictor ◽  
Pre Treatment ◽  
First Line Treatment ◽  
First Diagnosis

Abstract Introduction : Classical Hodgkin lymphoma (cHL) is the most common lymphoma affecting individuals under the age of 30. Despite improvements in standard treatment, 25-30% of patients still relapse after first-line treatment with ABVD. Relapsed patients are then typically treated by high dose chemotherapy and autologous stem cell transplantation (HDC/aSCT). However, this salvage therapy only cures approximately 50% of relapsed patients, and the mechanisms of second-line treatment failure are unclear. Moreover, currently no reliable biological markers are available to predict the outcome of HDC/aSCT at the time of relapse. The specific aim of this study is to compare diagnostic and relapse biopsies along with integrating clinical outcome data to uncover biology associated with resistance to first-line therapy, and identify prognostic markers for HDC/aSCT. Materials & Methods: NanoString Technologies digital gene expression profiling was used to ascertain the gene expression of 785 genes in formalin-fixed paraffin embedded tissue of 245 biopsies sampled from 174 cHL patients. This cohort included 90 patients with single biopsies performed at first diagnosis, 13 patients with single biopsies taken at relapse, and 71 patients with paired biopsies taken at both first diagnosis and at relapse. All 174 patients relapsed following uniform first line treatment with ABVD. Of these, 151 patients went on to receive salvage treatment that included HDC/aSCT. The 785 genes reflect biological signatures representative of cell types typically found in the microenvironment of cHL, and those previously reported to be associated with outcome in cHL. A tissue microarray was constructed containing all biopsies for immunohistochemistry (IHC) using CD68 antibodies (clone KP1). Spearman correlation tests were used for comparative gene expression analyses and IHC correlations. Differential expression analyses were performed using a non-parametric Wilcoxon test. Gaussian mixture models were used to cluster patients into poorly and well-correlated biopsy pairs. Outcome correlations were performed using the log-rank test and Cox regression analysis. Results : 24% of patients had a histological subtype transition between diagnostic and relapse biopsies with the most common transition (46%) from mixed cellularity (at diagnosis) to nodular sclerosis (at relapse). Comparative gene expression analysis revealed that 17 of the 71 patients (24%) had poorly correlated biopsy pairs (R2 < 0.75). Specifically, genes associated with macrophage differentiation (e.g. CD68, MARCO; FDR < 0.1) were found to be more highly expressed in the relapse biopsies compared to the matching samples at first diagnosis. CD68 IHC staining was well correlated with mRNA expression (p < 0.001) and confirmed that CD68+ cells were significantly more frequent in the relapse biopsies (p = 0.023). Patients with poorly correlated biopsy pairs had an inferior post-HDC/aSCT failure-free survival (5-y FFS: poorly correlated 39% vs. well correlated 68%; log-rank p = 0.005). Additionally, we applied our previously published 23-gene predictor (Scott, JCO, 2013), that was originally developed for pre-treatment biopsies, to the relapse biopsies. Using the published thresholds, 19% of patients were designated high-risk and had significantly inferior outcomes post-HDC/aSCT (5 year post-HDC/aSCT overall survival 40% vs. 82%, log-rank p = 0.001; 5 year post-HDC/aSCT failure-free survival 39% vs. 72%, log-rank p = 0.004). Conclusions : Our comparative analysis of cHL pre-treatment and relapse biopsies reveals differences at both the histopathological and molecular levels. We have identified novel factors, such as a poor correlation between paired biopsies and the 23-gene predictor, that are predictive of an inferior post-HDC/aSCT outcome. These findings suggest that re-biopsying patients at relapse will yield important biological insight and superior predictive power for second-line treatment failure. Disclosures Gerrie: F Hoffmann-La Roche: Other. Savage:F Hoffmann-La Roche: Other.

Activity of Idelalisib in High-Risk Follicular Lymphoma with Early Relapse Following Front Line Immunochemotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2744-2744 ◽  
Author(s):  
Ajay K Gopal ◽  
Brad S Kahl ◽  
Christopher Flowers ◽  
Peter Martin ◽  
Brian K Link ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Line Therapy ◽  
First Line Treatment

Abstract Background: Follicular lymphoma (FL) is the most common indolent NHL with a heterogenous natural history of disease and a median survival of 8 to 12 y, albeit ranging between 1 to 20 y. Casulo et al. (2015) identified a high-risk FL cohort of patients with progression of disease (POD) at ≤24 months following initiation of immunochemotherapy with R-CHOP. Idelalisib (Zydelig) is a first-in-class, highly selective, oral inhibitor of PI3Kd which is indicated for relapsed FL or SLL following receipt of at least two lines of systemic chemotherapy. Retrospective subgroup analysis of the idelalisib registrational trial NCT01282424 (101-09) of a cohort with early POD following immunochemotherapy was performed to assess possible activity of idelalisib in this population. Methods: A subset of 46 patients enrolled in study 101-09 were identified as having been diagnosed with FL and having received first-line immunochemotherapy, of which 37 experienced early POD, defined as starting second-line treatment within 24 months of initial first-line treatment. For the latter group, descriptive statistics of demographic and baseline characteristics and inter-treatment intervals in months as well as Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) following initiation of immunochemotherapy and idelalisib were calculated. Population: Demographic characteristics of these 37 patients included median (range) age at initiation of idelalisib of 64 (33-84) y and 18 (48.6%) females. Histologic grade at diagnosis included 33 (89.2%) with grades 1 or 2 as well as 4 (10.8%) with grade 3A, while 21 (56.8%) patients had a FLIPI score ≥3. The mean (s.d.) number of prior therapies was 3.4±1.4, with a range of 2 to 8, while first-line therapies included 21 (56.8%) patients who received R-CHOP-based regimens, 7 (18.9%) who received BR, and 5 (13.5%) who received R-CVP. Mean (s.d.) inter-treatment intervals included 12.5±6.1 months between first- and second-line for all patients, 9.7±9.3 months between second- and third-line for all patients, 11.9±12.0 months between third- and fourth-line for 24 (64.9%) patients, and 11.8±7.6 months between fourth- and fifth-line for 15 (40.5%) patients. Median (range) time from first-line therapy to idelalisib initiation was 30.3 (8.9-94.7) months; no patient received idelalisib as second-line therapy. Results: Best responses included 5 (13.5%) patients with CR, 16 (43.2%) with PR, 2 (5.4%) with SD, and 1 (2.7%) with PD; median duration of response for those with CR or PR was 11.8 months (95% CI: 3.8 months, not evaluable). There were 7 (18.9%) deaths and 21 (56.8%) PFS events in this group. Estimated probabilities of survival (s.e.) and progression-free status at 2 y following initiation of idelalisib were 79%±7% and 29%±10%, respectively. Median PFS was 11.1 months (95% CI: 5.5, 19.3 months). Estimated probability of survival (s.e.) at 5 years following initiation of first-line treatment was 79%±8%. Median overall survival from both initiation of first-line immunochemotherapy as well as with idelalisib was not reached during the course of this study. Conclusions: Idelalisib may have significant clinical activity in high-risk and doubly-refractive FL following early relapse status post first-line immunochemotherapy. Given the small size of the studied subset population which may not be representative, further characterization in additional patients is warranted to ensure the generalizability of this finding, including consideration of further investigational protocols featuring targeted therapies employed both as single agents and in combination. Figure 1. Overall Survival From Initiation of First-line Treatment Figure 1. Overall Survival From Initiation of First-line Treatment Figure 2. Overall Survival From Initiation of Idelalisib Figure 2. Overall Survival From Initiation of Idelalisib Figure 3. Progression-Free Survival From Initiation of Idelalisib Figure 3. Progression-Free Survival From Initiation of Idelalisib Disclosures Gopal: Gilead, Spectrum, Pfizer, Janssen, Seattle Genetics: Consultancy; Spectrum, Pfizer, BioMarin, Cephalon/Teva, Emergent/Abbott. Gilead, Janssen., Merck, Milennium, Piramal, Seattle Genetics, Giogen Idec, BMS: Research Funding; Millennium, Seattle Genetics, Sanofi-Aventis: Honoraria. Kahl:Roche/Genentech: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy; Cell Therapeutics: Consultancy; Celgene: Consultancy; Infinity: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy. Flowers:Infinity Pharmaceuticals: Research Funding; Genentech: Research Funding; Spectrum: Research Funding; Millennium/Takeda: Research Funding; Seattle Genetics: Consultancy; Spectrum: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding; AbbVie: Research Funding; Gilead Sciences: Research Funding; Pharmacyclics: Research Funding; Onyx Pharmaceuticals: Research Funding; Celegene: Other: Unpaid consultant, Research Funding; OptumRx: Consultancy; Gilead Sciences: Research Funding; Janssen: Research Funding; Acerta: Research Funding; Millennium/Takeda: Research Funding; Acerta: Research Funding; Infinity Pharmaceuticals: Research Funding; Janssen: Research Funding; Onyx Pharmaceuticals: Research Funding. Martin:Janssen: Consultancy, Honoraria; Acerta: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Bayer: Consultancy. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Ye:Gilead: Employment. Koh:Gilead: Employment. Abella:Gilead: Employment. Barr:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Abbvie: Consultancy; Gilead: Consultancy. Salles:Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy; Celgene Corporation; Roche and Gilead Sciences: Research Funding; Celgene Corporation; Roche: Speakers Bureau.

scholarly journals Immediate hypersensitivity reaction followed by successful oral desensitization to ursodiol

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Erika Yue Lee ◽  
Christine Song
Keyword(s):  
Hypersensitivity Reaction ◽  
Primary Biliary Cholangitis ◽  
Line Treatment ◽  
Second Line ◽  
Immediate Hypersensitivity ◽  
First Line ◽  
Case Presentation ◽  
Desensitization Protocol ◽  
First Line Treatment ◽  
Oral Desensitization

Abstract Background Immediate hypersensitivity reaction to ursodiol is rare and there is no previously published protocol on ursodiol desensitization. Case presentation A 59-year-old woman with primary biliary cholangitis (PBC) developed an immediate hypersensitivity reaction to ursodiol—the first-line treatment for PBC. When she switched to a second-line treatment, her PBC continued to progress. As such, she completed a novel 12-step desensitization protocol to oral ursodiol. She experienced recurrent pruritus after each dose following desensitization, which subsided after a month of being on daily ursodiol. Conclusion Immediate hypersensitivity reaction to ursodiol is uncommon. Our case demonstrated that this novel desensitization protocol to ursodiol could be safely implemented when alternative options are not available or have proven inferior in efficacy.

scholarly journals Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

2021 ◽  
Author(s):  
B. González Astorga ◽  
F. Salvà Ballabrera ◽  
E. Aranda Aguilar ◽  
E. Élez Fernández ◽  
P. García-Alfonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Option ◽  
Scientific Evidence ◽  
Treatment Options ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Effective Therapeutic Option ◽  
Line Setting ◽  
First Line Treatment

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

scholarly journals Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Braf Mutations ◽  
Mutational Status ◽  
First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

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