Markers of Responsiveness to ATG/CsA Therapy in Patients with Severe Aplastic Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1699-1699
Author(s):  
Abdo S. Haddad ◽  
Ania Jankowska ◽  
Theodore Ghazal ◽  
Sandra Smieszek ◽  
Ramon Tiu ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
First Line ◽  
Cd8 Cells ◽  
Overall Response ◽  
Flow Cytometric ◽  
Cell Clones ◽  
Immune Mediated

Abstract While ATG/CsA therapy results in a significant response rate in severe aplastic anemia (sAA), a substantial minority of patient remains refractory. Lack of response to intense immunosuppression (IS) may be a consequence of “non -immune” pathogenesis or be due inadequate intensity/duration of IS or exhaustion of stem cell reserves. Identification of markers of IS responsiveness would allow for a better patient selection and early application of stem cell transplantation (SCT). Various parameters of immune activation have been investigated but suitable makers of responsiveness to IS were not identified. Previously, we have shown a potential utility of flow cytometric analysis of T cell VB repertoire to identify expanded T cell clones that are involved in the autoimmune attack on hematopoietic progenitor and stem cells in immune-mediated bone marrow failure. Among 110 AA cases treated in our institution, 88 had sAA; 12 of them underwent early SCT while 74 were initially treated ATG/CsA. Of those patients, 60 received equine ATG (H-ATG) as a primary (N=56), or salvage modality (N=4) after rabbit ATG (R-ATG) with overall response rate (defined by transfusion independence and not fulfilling severity criteria) of 65% (66% as a first line). R-ATG was used in 23 patients as an initial (N=15) or salvage treatment (N=7) with overall response rate of 60% (61% as a first line, P=.88 as compared to H-ATG). For 24 patients (3 with mAA) we performed serial flow cytometric VB utilization profiling within CD3 CD4 and CD8 cells. All of these patients were minimally transfused and not infected at the time of initial testing. Prior to therapy, VB expansions (≥2 VB families) within CD4 and CD8 cells (defined as >mean+2xSD value for a given VB family in controls) indicative of the presence of potentially pathogenic T cell clones were present in 7/21 and 13/21 patients, respectively, P=.26. Nominally, CD4 and CD8 VB overrepresentations were 7% >mean+2xSD (1.7%-17.3%) and 9.26% (1.8%-24.5%), respectively. Within this specific sub-cohort of patients, the overall response rate measured at 6 months was 14/19 (73%). Response correlated with the presence of VB expansions prior to therapy; responders showed on average more and larger CD8 expansions (2 VB/patient, 0–3; 6.16% av. size, 1.8%-24.5%) and larger expansions vs. lower number of and smaller CD8 expansions (0.6 VB/patient, 0–3; 1.7% av. size, 5.7–11.4%) were seen in refractory patients (only 1/5 refractory patients had VB expansions). Conversely, 10/14 (71%) responses were seen in patients in with ≥2 CD8 VB expansion, only 1 patient responded but had no CD8 VB expansions. In contrast, only 1/5 (20%) ≥2 CD8 VB expansion were seen in refractory patients. Remarkably, hematologic improvement was associated with resolution of at least one significant VB expansion during monthly evaluations. In patients who relapsed reappearance of the original or new VB expansion within CD8 cells was seen. We conclude that CD8 VB expansions involving ≥2 VB families may predict of subsequent response to IS suggesting that VB typing may be a suitable monitoring tool for patients with immune-mediated AA.

Is First Line Single Agent Rituximab the Best Treatment for Indolent Non-Hodgkin’s Lymphoma? Update of a Multicentric Study Comparing Rituximab vs CNOP vs Rituximab Plus CNOP.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2431-2431 ◽  
Author(s):  
Silvia Rivas-Vera ◽  
Enrique Baez ◽  
Pedro Sobrevilla-Calvo ◽  
Severiano Baltazar ◽  
Francisco Tripp ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Disease Free Survival ◽  
First Line ◽  
Free Survival ◽  
Overall Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Free

Abstract Purpose: To evaluate efficacy, safety, Disease-Free Survival (DFS) and Overall Survival (OS) in patients with indolent non-Hodgkin’s lymphoma (NHL) treated with chemotherapy vs. immunotherapy vs immunochemotherapy as first-line therapy, an up-date report. Methods: Patients with indolent NHL were randomized to receive: (A) Rituximab x 6/w, (B) CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisone) x 6 or (C) R-CNOP x 6, at standard doses. Results: 195 patients were included, 183 are evaluable for OS and toxicity (A:62, B:55 and C:66), 144 are evaluable for overall response rate (ORR) and DFS (A:53, B:41 and C:50). Clinical characteristics: 89 male (45.6%), mean age 59±14 (±SD), 148 (75.9%) in stage (III/IV), without significant differences between groups. Overall Response Rate (CR+PR) was: A: 84.9%, B:83.4% and C:90% (P=0.545). Neutropenia grade 3/4 was more frequent in the chemotherapy groups: A: 4.8%, B: 23.6% and C:18.2% (P=0.001) as it was the infectious toxicity (grade 2/4): A:4.8%, B:5.5% and C:15.2% (P=0.07). DFS at 24 months was: A 68%, B:65% and C:70%, (P=0.93) and the OS was A:87%, B:84% and C:78%. P=0.89. Conclusions: We did not find any important differences, between groups, regarding the Overall Response Rate, Disease Free Survival and Overall Survival at 24 months. However, single agent rituximab was better tolerated, with less toxicity in comparison with the chemotherapy containing groups. Based on these findings, it maybe reasonable to use immunotherapy only, as first-line therapy for patients with indolent NHL.

High Overall Response Rate in Calcineurin Inhibitor-Free Treatment with the mTOR Inhibitor Everolimus in Advanced Extensive Chronic GvHD after Allogeneic Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2210-2210 ◽  
Author(s):  
Anne Klink ◽  
Kristina Schilling ◽  
Katrin Rapp ◽  
Klaus Höffken ◽  
Herbert G. Sayer
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Overall Response Rate ◽  
Mtor Inhibitor ◽  
Response Rate ◽  
Complete Response ◽  
Overall Response ◽  
Free Treatment ◽  
Unrelated Donors ◽  
Grade Ii

Abstract Background: The mammalian target of rapamycin (mTOR) inhibitor Everolimus (RAD001, Certican®) is a new immunosuppressive drug and beside of sirolimus used and approved in solid organ transplantation. Recently, it was reported that mTOR-inhibitors in combination with calcineurin inhibitors (CNI) showed clinical responses in chronic graft-versus-host disease (cGvHD). In this single centre retrospective analysis, we report on 29 patients (pts) with severe cGvHD treated with Everolimus without CNI. Patients and Methods: Twenty-nine pts (17 AML, 3 CML, 4 ALL, 3 CLL, 2 NHL) with a median age of 44 years [range: 25–61] underwent allogeneic stem cell transplantation between September 1999 and August 2007. Myeloablative conditioning was used in 21 pts, reduced-intensity conditioning in 8 pts. Except for one patient receiving bone marrow, all pts received peripheral blood stem cells for transplantation. Family donors (2 non-fully HLA matched) were used in 7 pts (24%) and unrelated donors (7 non-fully HLA-matched) in 22 pts (76%). GvHD-prophylaxis consisted of CNI (cyclosporine or tacrolimus) in 4 pts, CNI+Methotrexate (MTX) in 8 pts, CNI+Mycophenolate (MPA) in 8 pts and CNI+MPA+MTX in 9 pts. Antithymocyte globulin (ATG) as in vivo T-cell depletion was used in 9 pts. Cytomegalovirus (CMV)-serostatus was positive in 14 pts, with seronegative donors in 5 pts. Acute GvHD occurred in 27/29 (93.3%), grade II-IV in 25 (86.2%). At the same time, CMV reactivation/infection was observed in 11 pts and thrombotic microangiopathy (TMA) in 3 pts. All pts developed severe cGVHD with extensive disease. Organ involvement included skin with scleroderma in 21 pts, mucous membranes in 22 pts, eyes in 22 pts, lungs in 8 pts, liver in 11 pts, gut in 9 pts and arthralgia in 6 pts. At the time of treatment start with everolimus (0.75 mg Certican ® twice a day orally), CNI medication was stopped. The intended plasma therapeutic levels of everolimus were 3–8 mg/l. In addition all pts received prednisone and in 18 pts (62%) MPA as third immunosuppressive agent was continued. Results: Median treatment duration was 8.4 months [range: 2.5–21.7]. None of the pts developed CMV disease or TMA. Adverse events were: arterial hypertension in 1 patient, atrial fibrillation in 1 patient, pneumonia in 1 patient, sinusitis in 1 patient, herpes labials infection in 1 patient, renal insufficiency grade II in 2 pts and myalgia in 2 pts. 96.6% are still alive, 1 patient (3.4%) died due to relapse of ALL. Two pts (6.9%) achieved a complete response of their cGvHD and 18 pts (62.1%) a partial response resulting in an overall response rate of 69.0% (n=20) according to the recent consensus NIH report (Biol. Blood Marrow Transplant. 2006 May; 12(5): 491–505). No change was observed in 3 pts (10.3%) and progression occurred in 6 pts (20.7%). Complete response in HLA-identical related donors was 20% (1/5) and with HLA-matched unrelated donors was 6.7% (1/15). 100% (n=2) of pts with a HLA-mismatched related donor achieved a partial remission and 85.7% (n=6) of pts with a HLA-mismatched unrelated donor. The gender of recipient or donor did not impair the observed responses with everolimus. Prednisone could be tapered in 62.1% of all pts (18/29). In the triple combination with MPA, MPA could be tapered in 22.2% (4/18) and could be stopped in 38.9% (7/18). Conclusions: A CNI-free treatment of advanced extensive cGvHD with everolimus seems to be feasible and effective with a high overall response rate of nearly 70 %. It should be emphasized that a low toxicity profile without TMA was observed. Our data supports further clinical and immunological investigations with m-TOR inhibitor everolimus in treating GvHD.

Low Absolute Lymphocyte Count Predicts Chemotherapy Response and Survival In Peripheral T-Cell Lymphoma, NOS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3135-3135
Author(s):  
Yu Ri Kim ◽  
yun Deok Kim ◽  
Jin Seok Kim ◽  
June-Won Cheong ◽  
soo Jeong Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Factor ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Independent Prognostic Factor ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Overall Response

Abstract Abstract 3135 Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS) is heterogenous groups of aggressive T-cell lymphoma and treatment outcome is dismal. Lymphopenia is an independent prognostic factor for survival for B-cell lymphoma. The ALC at diagnosis on survival in T-cell lymphoma has not been studied. Thus, we studied the role of ALC at diagnosis on clinical outcome in patients with PTCL, NOS. Between 2001 and 2009, 32 patients with PTCL, NOS reviewed for the study. Median patient age was 57 (range 34–78) years. Median ALC at the time of diagnosis was 1.54 (range 0.41–12.64×109/L). Patients were divided two groups according to ALC count 1.0 ×109/L. Ten patients (31%) had lower ALC at diagnosis. Median follow up duration was 299 days (range 11–2164 days). Overall response rate was 61.5% (16 of 26 patients) and complete response (CR) rate was 42% (11 of 26 patients). Only two patients reached CR in low ALC group.There was no significant difference in overall response rate because of small number of patients. Superior overall survival was observed with an ALC 1.0 × 109/L (N = 22) versus an ALC < 1.0 × 109/L (N=10) (median OS: not reached vs 242 days, OS rates at 5 years, 57% vs 0%, p =0.016, respectively). Multivariate analysis demonstrated ALC to be an independent prognostic indicator for OS (Hazard Ratio 3.5, 95% confidence intervals 1.2–10.2; p<0.019) when compared to the International prognostic index (IPI) and Prognostic Index for PTCLU (PIT). This study suggested that low ALC is an independent prognostic factor for survival in patients with PTCL, NOS. Disclosures: No relevant conflicts of interest to declare.

Update of the NCI multiinstitutional phase II trial of romidepsin, FK228, for patients with cutaneous or peripheral T-cell lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8027-8027 ◽  
Author(s):  
R. Piekarz ◽  
R. Frye ◽  
J. Wright ◽  
W. Figg ◽  
S. Allen ◽  
...  
Keyword(s):  
T Cell ◽  
Histone Deacetylase Inhibitors ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Overall Response ◽  
Prior Therapy

8027 Background: The histone deacetylase inhibitors (HDIs) are a class of differentiating agents undergoing clinical testing. Like other HDIs, romidepsin (FK228) modulates expression of genes involved in cell cycle regulation and markers of differentiation in cancer cell lines, leading to induction of differentiation or apoptosis. Romidepsin has demonstrated clinical activity in patients with T-cell lymphoma. Methods: Patients with CTCL (42) or PTCL (36) were enrolled in the NCI multi-institutional trial and assigned to cohorts based on extent of prior therapy and pathology. Romidepsin is administered on days 1, 8, and 15 of a 28 d cycle with a starting dose of 14mg/m2. Responses for patients with PTCL are measured using Cheson criteria, and CTCL using RECIST criteria. Results: Cohort one, composed of 27 patients who had previously received no more than 2 prior cytotoxic regimens of chemotherapy, has completed enrollment. Responses observed include 3 patients with CR and 7 patients with partial responses, yielding an overall response rate of 37%. Of note, responses were observed independent of stage of disease. Among 18 patients with stage IV disease, 6 patients had a complete or partial response, including 3 patients with Sézary syndrome. When including patients with greater than 2 prior cytotoxic regimens, the overall response rate was 31%. A replicate arm has been opened with the goal of confirming the response rate observed in the first cohort. Response data have not been evaluated from this arm at this time. Responses observed in 36 patients with refractory or relapsed PTCL includes 3 patients with CR and 8 patients with partial responses, comprising an overall response rate of 30%. Responses were observed independent of prior therapy, with some patients having undergone prior stem-cell transplant. Molecular endpoint analysis was performed on peripheral mononuclear cells (PBMNCs) and tumor biopsies from treated patients evaluating histone acetylation and changes in gene expression. Conclusions: Romidepsin as a single agent appears to have significant single agent activity in patients with CTCL and PTCL. Combination therapy with romidepsin may increase efficacy and should be pursued. This protocol remains open to accrual. No significant financial relationships to disclose.

scholarly journals Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study

2015 ◽  
Vol 33 (23) ◽  
pp. 2492-2499 ◽  
Author(s):  
Owen A. O'Connor ◽  
Steven Horwitz ◽  
Tamás Masszi ◽  
Achiel Van Hoof ◽  
Peter Brown ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Working Group ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Standard Of Care ◽  
Pivotal Phase ◽  
Overall Response ◽  
International Working Group

Purpose Peripheral T-cell lymphomas (PTCLs) represent a diverse group of non-Hodgkin lymphomas with a poor prognosis and no accepted standard of care for patients with relapsed or refractory disease. This study evaluated the efficacy and tolerability of belinostat, a novel histone deacetylase inhibitor, as a single agent in relapsed or refractory PTCL. Patients and Methods Patients with confirmed PTCL who experienced progression after ≥ one prior therapy received belinostat 1,000 mg/m2 as daily 30-minute infusions on days 1 to 5 every 21 days. Central assessment of response used International Working Group criteria. Primary end point was overall response rate. Secondary end points included duration of response (DoR) and progression-free and overall survival. Results A total of 129 patients were enrolled, with a median of two prior systemic therapies. Overall response rate in the 120 evaluable patients was 25.8% (31 of 120), including 13 complete (10.8%) and 18 partial responses (15%). Median DoR by International Working Group criteria was 13.6 months, with the longest ongoing patient at ≥ 36 months. Median progression-free and overall survival were 1.6 and 7.9 months, respectively. Twelve of the enrolled patients underwent stem-cell transplantation after belinostat monotherapy. The most common grade 3 to 4 adverse events were anemia (10.8%), thrombocytopenia (7%), dyspnea (6.2%), and neutropenia (6.2%). Conclusion Monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication.

scholarly journals The mTORC1 inhibitor everolimus has antitumor activity in vitro and produces tumor responses in patients with relapsed T-cell lymphoma

Blood ◽  
2015 ◽  
Vol 126 (3) ◽  
pp. 328-335 ◽  
Author(s):  
Thomas E. Witzig ◽  
Craig Reeder ◽  
Jing Jing Han ◽  
Betsy LaPlant ◽  
Mary Stenson ◽  
...  
Keyword(s):  
T Cell ◽  
Antitumor Activity ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Mtor Pathway ◽  
T Cell Lymphoma ◽  
Overall Response ◽  
Key Points

Key Points The mTOR pathway is constitutively activated in the TCL cells and is responsible for TCL proliferation. This is first trial to demonstrate that mTORC1 inhibitors (everolimus) have substantial antitumor activity (44% overall response rate) in patients with relapsed TCL.

scholarly journals Metronomic Chemotherapy Is Effective and Well Tolerated in Relapsed/Refractory Elderly Patients with Aggressive B- and T-Cell Lymphomas

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5080-5080
Author(s):  
Maria Christina Cox ◽  
Elena Cavalieri ◽  
maria Paola Bianchi ◽  
Raffaele Porrini ◽  
Virginia Naso ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Elderly Patients ◽  
Overall Response Rate ◽  
Hospital Admissions ◽  
Response Rate ◽  
Induction Phase ◽  
Overall Response ◽  
T Cell Lymphomas ◽  
Grade 3

Abstract BACKGROUND: Elderly patients with Relapsed/Refractory (R/R) aggressive Large B-cell lymphoma (LBCL) and Peripheral T-cell lymphomas (PTCL), are commonly treated with intravenous conventional chemotherapies, which are often poorly tolerated and of short-lasting efficacy. Therefore only few fit-elderly patients might undergo intensive treatments with curative intent. Metronomic chemoterapy (MTN-CHT) is a new way of administering old drugs at low doses with only short chemotherapy free intervals. MTN-CHT may be combined with new targeted molecules, immunotherapies and radiotherapy. Although very few reports on MTN-CHT in LBCL and PTCL have been published existing data suggest that these lymphomas might respond to this approach. AIM: We aimed at demonstrating the efficacy and safety of MTN-CHT in a retrospective series of elderly patients with LBCL and PTCL, unfit for conventional treatments. PATIENTS AND TREATMENTS: From October 2008 up to May 2015 we treated elderly patients with R/R LBCL, Follicular Lymphoma(FL) and PTCL with MTN-CHT based regimen. Eligible patients should have given written informed consent, have a Performance Status=0-3, a life expection >2 months, be able to take oral therapy and have a care-giver. We used three different MTN schedules: 1] Provecip; 2] Vinblastine+Endoxan+Etoposide+Prednisone (VEED) and in the last two years an all-oral schedule 3] Navelbine+Endoxan+Etoposide+Prednisone (DE-VEC). All three schedules of MTN-CHT consisted of an induction phase of six months followed by a maintenance phase administered until progression or excessive toxicity. Rituximab was added to the induction phase for those patients characterized by CD20 expression. Thrombosis prophylaxis was carried out with aspirin or LMWH. RESULTS Patients features: LBCL=21; PTCL=7, FL=3; Age=77y (median, range 62-90), Previous CHT=2 (median, range 0-5) refractory to last CHT= 43%. MTN-CHT: 8 pts were treated with schedule 1], 8 pts with schedule 2] and 15 pts with schedule 3]. Outcome: in aggressive B and T-cell lymphomas (n=28pts) with all schedules Overall Response Rate = 62%, Complete Remission rate = 36%; Progression Free Survival = 8 months, Median Duration of Response (DOR)= 10 months. Overall Response Rate and Complete Remission in the subset treated with the all-oral DE-VEC schedule were 66% and 50% respectively. Serious adverse events: Extra hematologic toxicity grade 3-4: pulmonary embolism in 1pts; hematological toxicity of grade 3-4 and/or neutropenic infections in 6 patients 5 of whom had >2 previous conventional chemotherapies. The use of DE-VEC all-oral schedule reduced the number and the durations of day-hospital admissions. CONCLUSION Although our series is limited, these results suggest that MTN-CHT in elderly patients with R/R LBCL, PTCL and FL might achieve favorable results in terms of activity, toxicity and costs due to hospital admissions. With MTN-CHT most of the patients did not need G-CSF. Notably, patients who had had >2 lines of chemotherapies may be at very high risk of prolonged cytopenia and infections during MTN-CHT. Since the all-oral DE-VEC schedule was particularly manageable and active we believe that this combination deserve further investigation in aggressive lymphomas. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽  
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.

Cetuximab plus docetaxel-cisplatin (DC) as first-line treatment for locally advanced or metastatic gastric cancer: Preliminary results of a phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15592-e15592
Author(s):  
J. Fahlke ◽  
K. Ridwelski ◽  
A. Florschuetz ◽  
E. Kettner ◽  
M. Leithaeuser ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Published Data ◽  
First Line ◽  
Overall Response ◽  
Grade 3

e15592 Background: Based on promising published data, this multicenter, phase II study was initiated to investigate a combined treatment using DC and cetuximab in the first-line setting for patients with gastric cancer. Methods: Patients aged 18–75 years with stage III (T4, nonresectable) or stage IV gastric cancer, ECOG performance status (PS) ≤2, and life expectancy ≥3 months were recruited to receive cetuximab (400 mg/m2 on day 1 then 250 mg/m2 q1w) and DC (D 75 mg/m2 and C 75 mg/m2; both as 1-h infusions on day 1 and then q3w). Treatment was stopped in the event of disease progression, intolerable toxicity, or consent withdrawal. Tumor staging was performed after cycle 3 and then every 12 weeks. The primary endpoint was overall response rate and secondary endpoints included time to progression, overall survival and toxicity. Planned accrual was 79 patients. A per-protocol interim response analysis was planned for the initial 20 evaluable patients. Results: Preliminary data are available for 30 patients; median age 64 [range: 40–73] years; median ECOG PS 1 [range: 0–2]; adenocarcinoma 87%. Median cycles administered were 3 [range: 1–14] and the median follow-up was 1.63 months. The overall response rate was 27.3% (complete response, n=1; partial response, n=5). Stable disease was observed in 10 patients, and disease progression in 6 patients. The most relevant NCI-CTC grade 3–4 hematologic events per patient were leukopenia and neutropenia (73%), anemia (13%), and febrile neutropenia (10%). Major grade 3–4 nonhematologic toxicities were nausea (30%), vomiting (20%), diarrhea (13%), acne (13%), and fatigue (13%). Conclusions: DC and cetuximab were well tolerated and resulted in promising response rates and a predictable toxicity profile. The study is ongoing. No significant financial relationships to disclose.

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