Systemic Mastocytosis. A GIMEMA Multicenter Survey.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4874-4874
Author(s):  
Livio Pagano ◽  
Caterina Giovanna Valentini ◽  
Pellegrino Musto ◽  
Morena Caira ◽  
Michela Rondoni ◽  
...  
Keyword(s):  
Mast Cell ◽  
Point Mutation ◽  
Systemic Mastocytosis ◽  
Response To Treatment ◽  
First Line ◽  
Kit Mutation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Multicenter Survey ◽  
Third Line

Abstract To evaluate clinical and biological features, treatments and outcome of patients(pts) with Systemic Mastocytosis(SM). A retrospective study (1995–2006) about pts with SM admitted in 14 Italian hematology divisions in tertiary cares or university hospitals. 30 cases of SM were collected(median age 62 y.o.; M/F 14/16) and classified according to the WHO criteria: Mast Cell Leukemia in 14 pts, Aggressive SM in 12 and Indolent in 3; the remaining one had SM with associated clonal non-mast cell-lineage hematologic disease. Skin was the principal extramedullary organ involved (19 pts) followed by spleen(15), liver(13), and cardiovascular system(12). Molecular biology studies were performed in 22 pts: 15 showed the c-kit point mutation D816V; in another patient a different c-kit mutation was found while in 3 pts additional gene defects and karyotype abnormalities were recognized. Treatments were heterogeneous, and the same patient could have received different therapies after failure of the previous one. Imatinib(400 mg/day) was used in 17 pts (11 as first line therapy, 5 and 1 as second and third line respectively); interferon-alpha(3×3 MU s.c. weekly) was employed in 7 patients(4 as first line therapy, 2 as second and 1 as third line); 2-CDA(0.14 mg/kg) was administered in 3 pts(1 as first, 1 as second and 1 as third line therapy); 2 patients underwent HSCT as second and third line respectively. Data about response to treatment are reported in the table. The overall response rate to imatinib was of 30%, registering 1 complete remission(CR) and 4 partial remissions. All but one responsive patients did not present c-kit point mutation. Three pts(10%) died for progression of SM; a fourth patient in CR died for accidental causes. The actuarial Kaplan-Meier curve at 10 years showed an overall-survival of 87%. Conclusions: SM is a rare disease, characterized by severe and life-threatening mediator-related symptoms but with a low mortality rate. D816V c-kit mutation is frequent and associated with resistance against imatinib: only 1 patient showed a CR. Of note 2-CDA has shown interesting clinical response: all 3 treated pts showed a clinical improvement. Because of the rarity of SM, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies; it is possible that new tyrosine kinase inhibitors could allow to achieve clinical and molecular remission of disease, crossing resistence to imatinib due to c-kit mutation, in order to improve above all quoad valitudinem prognosis of these pts. Response to treatments. DRUGS CR PR Stable Unrespons. N.E. TOTAL Imatinib 1 4 5 3 4 17 INF-alpha 0 1 1 5 0 7 2-CDA 0 3 0 0 0 3 Conventional CTX 0 1 2 4 1 8 Allo-HSCT 2 0 0 0 0 2 Wait & Watch 0 0 6 2 0 8

Cytoreductive Therapy in Systemic Mastocytosis: Outcome Analysis and Response Prediction in 134 Consecutive Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1759-1759
Author(s):  
Ken-Hong Lim ◽  
Animesh D. Pardanani ◽  
Joseph H Butterfield ◽  
Chin Yang Li ◽  
Ayalew Tefferi
Keyword(s):  
Mast Cell ◽  
Imatinib Mesylate ◽  
Median Duration ◽  
Systemic Mastocytosis ◽  
Myeloid Cells ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Duration Of Response ◽  
Immature Myeloid Cells

Abstract Background: Current therapy in adult systemic mastocytosis (SM) includes observation alone, topical therapy for cutaneous disease, symptomatic non-cytoreductive therapy and cytoreductive therapy. The latter involves several drugs whose individual merit in the treatment of SM has not been well characterized. Patients and Methods: Diagnosis of SM was according to the 2001 WHO criteria (World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues, p 1–351. Lyon, France: IARC Press; 2001). Response to cytoreductive therapy was assessed by consensus criteria (Eur J Clin Invest.2007;37:435). The study population was selected from a series of 342 adult SM patients referred to our institution and seen between 1964 and 2008. KITD816V mutation analysis was performed by DNA sequencing. Results: A total of 134 study patients received treatment that included at least one cytoreductive drug as either first-line (n=105) or second-line (n=29) therapy. Interferon-alpha with or without prednisone (n=58), hydroxyurea (n=43), imatinib mesylate (n=42) and 2-chlorodeoxyadenosine (n=26) were the most frequently used cytoreductive agents accounting for 120 of the 134 study cases; the remaining 14 patients received other cytoreductive drugs, none of which were effective. i. Interferon-alfa (IFN-a) with or without prednisone IFN-a with or without prednisone (24 and 34 patients, respectively) was given to 12 patients with indolent SM (ISM), 14 aggressive SM (ASM), and 32 SM with associated clonal hematological non-mast cell lineage disease (SM-AHNMD). For all 58 patients receiving therapy, complete (CR), major (MR), and partial (PR) response/regression were achieved in 3, 7, and 14 patients, respectively, for an overall response rate (ORR) of 41%. ORR in ISM, ASM, and SM-AHNMD was 50%, 43%, and 38%, respectively. Median duration of response was 12 months (range, 1–117 months). Anemia and elevated ESR were significantly associated with inferior ORR; 29% vs. 56% (p=0.04) and 14% vs. 57% (p=0.01), respectively. BM detection of KITD816V did not appear to affect response rates (p=0.4). ii. Hydroxyurea (HU) HU was given to 2 ASM, 40 SM-AHNMD and 1 mast cell leukemia (MCL) patients. The drug was used as first-line therapy in 30 patients. MR and PR were achieved in 1 and 8 SM-AHNMD patients, respectively (ORR=21%). Median duration of response was 37 months (range, 5–84 months). iii. Imatinib mesylate (IM) in patients with SM and associated eosinophilia IM was given to 22 SM patients who had associated eosinophilia (SM-eos): 2 had ISM, 2 ASM, and 18 SM-AHNMD. The drug was used as first-line therapy in 9 patients. Ten of the 22 patients with SM-eos were known to harbor the FIP1L1-PDGFRA fusion mutation and all responded to IM (ORR=100%). None of 5 FIP1L1-PDGFRA-negative SM-eos patients had a response to IM. In the remaining 7 patients with unknown mutation status, 4 patients had a response to IM (1 CR, 1 MR, and 2 PR). iv. IM in patients with SM not associated with eosinophilia IM was administered to 20 SM patients without associated eosinophilia (7 ISM, 2 ASM, 10 SM-AHNMD, and 1 MCL). Response was documented in 4 (20%) patients (1 CR, 1 MR, and 2 PR) including 1 with ISM, 2 with ASM and 1 with SM-AHNMD. Median duration of response was 19.5 months (range, 9–69 months). Two patients developed interstitial pneumonitis. v. 2-Chlorodeoxyadenosine (2-CdA) 2-CdA was given to 10 ISM, 3 ASM, and 13 SM-AHNMD patients; the drug was used as first-line therapy in 8 patients. CR, MR and PR were achieved in 1, 7, and 4 patients, respectively (ORR=46%). ORR in ISM, ASM, and SM-AHNMD was 50%, 33%, and 46%, respectively. Median duration of response was 11 months (range, 3–74 months). Presence of leukocytosis (WBC > 10 x 109/L), monocytosis (absolute monocyte count > 0.9 x 109/L) or circulating immature myeloid cells was significantly associated with inferior response; 13% vs. 61% (p=0.02); 11% vs. 69% (p=0.006) and 0% vs. 71%, (p=0.001), respectively. Response was not affected by BM detection of KITD816V (p=1.0). Conclusions: Both IFN-a and 2-CdA are reasonable treatment options, with comparable efficacy, for symptomatic SM including the subcategories of ISM, ASM and SM-AHNMD. IFN-a response was significantly better in the absence of anemia or elevated ESR. 2-CdA response was similarly better in the absence of leukocytosis, monocytosis or circulating immature myeloid cells. The therapeutic value of IM was limited to FIP1L1-PDGFRA-positive disease.

scholarly journals Treatment of Patients with Aggressive Systemic Mastocytosis, Mast Cell Leukemia and Mast Cell Sarcoma: A Single Center Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1769-1769 ◽  
Author(s):  
Karoline V. Gleixner ◽  
Peter Valent ◽  
Wolfgang R. Sperr
Keyword(s):  
Mast Cell ◽  
Median Survival ◽  
Clinical Course ◽  
Systemic Mastocytosis ◽  
Cell Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mast Cell Leukemia

Abstract Aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL) and mast cell sarcoma (MCS) are rare, life-threatening mast cell disorders, characterized by an aggressive clinical course, drug resistance and a poor survival. Established disease-modifying therapies include interferon-alpha (INF-A), cladribine (2CdA) and midostaurin (PKC412). However, these treatment approaches are unable to exert curative effects in advanced mastocytosis. Intensive therapy, including poly-chemotherapy and hematopoietic stem cell transplantation (HSCT) have also been suggested for patients with rapidly progressing ASM and MCL (Ustun et al, J Clin Oncol 2014;32:3264-3274). However, little is known about long-term outcome and survival in these patients. We analyzed the clinical course and treatment responses in 24 patients with ASM, MCL and MCS seen at the Medical University of Vienna between May 1994 and December 2017. According to World Health Organization criteria, patients were diagnosed as ASM (n=11), ASM with associated chronic myelomonocytic leukemia (ASM-CMML, n=6), ASM with associated chronic eosinophilic leukemia (ASM-CEL, n=1), MCL (n=4) and MCS (n=2). The median age at diagnosis was 59 years (range 21-90 years) and the f:m ratio was 1:2.4. Patients received first-line therapy with INF-A (3x106 units three times a week, n=8), 2-CdA (0.13 mg/kg, days 1-5, n=5); CLAG (cladribine 5mg/m2, days 1-5, ARA-C 2g/m2 day 1-5, G-CSF, 300 µg from day 6 until recovery; n=2), alternating 2CdA and midostaurin (n=2), midostaurin alone (2x100 mg/day, n=2), FLAG (fludarabine, 30mg/m², days 1-5; ARA-C 2 g/m² days 1-5; G-CSF 300µg from day 6 until recovery, n=1) and brentuximab-vedotin (1.6 mg/kg every 3 weeks, n=1). In 3 patients (ASM, n=1; MCL, n=2) no therapy could be administered because of poor performance status. Detailed information on therapies and responses in our patients are provided in Figure 1. In 17 of 21 patients (81%) a response to therapy was observed, namely a complete remission (CR) in one female MCL patient, age 54 yrs (years) receiving 2 cycles of FLAG; a good partial response (GPR) of the remaining tumor mass (after surgery) in one female patient with MCS aged 33 yrs after 2 cycles of CLAG; a partial response (PR) in 5 additional patients; and a stable disease (SD) in 9 patients (Figure 1). Two patients, one female ASM patient, age 54 yrs with PR after 6 cycles of 2CdA and one female patient with MCS, age 30 yrs, with a GPR after CLAG, underwent HSCT and achieved long-term CR under maintenance with midostaurin. Median survival until loss of response to first-line therapy was 20 months (range: 3-73 months). Interestingly, in all 4 patients who had received both 2CdA and midostaurin, no progression of the disease occurred. In the follow up, 3 patients are still alive, 7 developed a secondary acute myeloid leukemia (sAML) and in one patient with ASM-CMML, the CMML component progressed without overt AML. Three patients died due to unrelated (non-SM) events (age at death: 93, 90, and 67 yrs). The patient with CR following FLAG had a relapse of MCL after 4 months. In 3 patients receiving IFN-A, the disease showed progression under therapy and in 2 patients receiving midostaurin, therapy had to be withdrawn due to treatment-related toxicity prior to response evaluation. Interestingly, the risk to develop sAML was significantly higher in patients with ASM/CMML or ASM/CEL (71.4%) compared to patients with ASM (27.2%) or MCL/MCS without an associated hematologic neoplasm (0%) (p<0.05). Salvage therapy in patients with progressive disease (PD or toxicity under first-line therapy, n=4; PD/relapse following response to first-line therapy in patients eligible for further therapy, n=10) included 2CdA, polychemotherapy, INF-A, azacitidine and hydroxyurea. The median number of treatment lines of salvage therapy was 1.7 (range 1-4) and resulted in a median duration of response of 8 months (range: <1 to 44 months). The median survival of patients developing sAML was 4 months and was markedly shorter compared to patients without sAML (median survival 13 months). In conclusion, treatment of ASM, MCL and MCS remains a clinical challenge and unmet treatment-need. The combination of conventional therapy such as chemotherapy with novel tyrosine kinase inhibitors and/or HSCT may be a new promising approach in these patients and may lead to cure in some of them. However, controlled studies are necessary to confirm this hypothesis. Figure 1. Figure 1. Disclosures Valent: Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Sperr:Novartis: Honoraria; Pfizer: Honoraria; Daiichi Sankyo: Honoraria.

Cisplatin as first-line therapy for metastatic breast cancer.

1988 ◽  
Vol 6 (12) ◽  
pp. 1811-1814 ◽  
Author(s):  
G W Sledge ◽  
P J Loehrer ◽  
B J Roth ◽  
L H Einhorn
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
The United States ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Ii Studies ◽  
Third Line

Cisplatin has had only minimal activity when used as second- and third-line chemotherapy for metastatic breast cancer (MBC). There have been no phase II studies in the United States evaluating cisplatin in patients with MBC with no prior chemotherapy. We therefore treated 20 consecutive patients with cisplatin 30 mg/m2/d for four days every 3 weeks for a maximum of six courses. We obtained partial responses in nine of 19 evaluable patients (47%), with responses in liver, lung, and soft tissue indicator lesions. Our data suggest that cisplatin has substantial single-agent activity as front-line therapy in MBC, and should be considered for inclusion in first-line combination chemotherapy regimens.

Health related quality of life (HRQOL) evaluated with the EORTC C30 questionnaire in first line therapy of elderly patients with chronic lymphocytic leukemia (CLL): Results of a phase III trial of the German CLL Study Group (GCLLSG)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7572-7572 ◽  
Author(s):  
B. F. Eichhorst ◽  
R. Busch ◽  
M. Hallek
Keyword(s):  
Social Functioning ◽  
Age Groups ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Response To Treatment ◽  
First Line ◽  
Elderly Age ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

7572 Background: The GCLLSG evaluated the efficacy of fludarabine (F) versus (vs.) chlorambucil (Clb) in first line therapy of older patients with advanced CLL. HRQOL was evluated by using the EORTC C30 questionnaire. Methods: Pts were randomized to receive 6 courses of F (25 mg/m²/day (d) IV for 5d; 92 pts) or 12 months (mo) of Clb (0.4–0.8 mg/kg/d PO, every 15d; 99 pts). All pts were previously untreated, aged between 65 and 79 years and in advanced stage Binet C or symptomatic Binet B or A. Primary endpoints were overall survival (OS) and progression free survival (PFS), secondary endpoint was HRQOL. The EORTC C30 questionnaire (version 2.0) was sent to all patients at baseline and after 6, 12 and 24 mo. Scores (0–100) for 15 different measures (1 global HRQOL, 5 functional, 3 symptom and 6 single item scales) were evaluated at each time point. Results: F induced significantly higher response rates and prolonged the PFS, while no significant difference in OS was observed. At baseline 130 of 191 pts (68%) completed the questionnaires followed by more than 80% at mo 6 to 24. Compliance rates were similar in both treatment arms. Between pts completing questionnaires or not no statistically significant differences in perfomance status, age, stage or response to treatment were observed. HRQOL differences in comparison to baseline values were significantly improved after F treatment in global HRQOL, role and social functioning after 12 months as shown by the table. Responders had a significantly better global HRQOL and social functioning as well. Except for an impaired physical functioning no differences in HRQOL were observed between different age groups (65–69, 70–74, 75–79). Conclusion: Elderly F treated patients with CLL showed improvement inglobal HRQOL. Elderly age groups had a similar HRQOL as younger age groups. [Table: see text] [Table: see text]

scholarly journals Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5880-5880
Author(s):  
Nathan H Fowler ◽  
Yanni Hao ◽  
Stephen Lim ◽  
Guifang Chen ◽  
Frank Li ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line ◽  
Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

Presentation and treatment of HER2-positive metastatic breast cancer patients already treated with adjuvant trastuzumab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 619-619
Author(s):  
Davis Yuri Torrejon ◽  
Serena Di Cosimo ◽  
Gessami Sanchez-Olle ◽  
Judith Balmaña ◽  
Meritxell Bellet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Median Time ◽  
Metastatic Breast ◽  
Response To Treatment ◽  
First Line ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2

619 Background: The introduction of trastuzumab in the clinical armamentarium has profoundly changed the natural history of HER2 positive breast cancer (BC). However, about 15% of patients with HER2 early BC treated with adjuvant trastuzumab continue to relapse. We aimed to analyze these patients with respect to clinical presentation and response to treatment. Methods: Data were retrieved from the institutional BC database of Vall d’Hebron. All the cases relapsing after exposure to adjuvant trastuzumab were analyzed. Change in expression of hormone-receptor (HR) and HER-2 status between primary tumour and corresponding local recurrence or distant metastasis was also evaluated Results: A total of 270 patients were identified. Twenty-six patients (9.6%) relapsed (Table). Overall median time from diagnosis to relapse was 27.1 months (24.1-30.1) being 29.1 months (14.3-44.1) in HR positive and 23.1 (9.9-36.2) in HR negative cases (p=0.037). Median time from last dose of trastuzumab to relapse was 7.6 (2.7-12.7) months, being 10.6 (0-27.9) and 3 months (0-7.6) in HR positive and negative cases, respectively (p=0.026). Sixteen patients have already progressed to first-line therapy with a median time to progression (TTP) of 7.4 months with no statistical difference among HR positive and HR negative (4.4 and 9.8 months, p=0.3). No difference was found in TTP to first line therapy among early (before 12 months) and delayed (after 12 months) progression on adjuvant trastuzumab. Among the 17 cases with primary tumor and matched metastatic biopsy, HER-2 negativization was detected in 2 cases; whereas a change in estrogen and progesterone receptors was seen in 17.6% and 29.4% of cases, respectively. Conclusions: Patients with HER2+/HR negative treated with adjuvant trastuzumab seems to have a significantly shorter time to relapse compared with the HER2+/HR+ tumors. In these patients biopsy of metastatic lesions might help to define the best treatment options. [Table: see text]

Non Predictive Value of An Initial Tc-99m-MIBI Scintigraphy On the Prediction of Therapeutic Outcome in Non Hodgkin and Hodgkin Lymphoma: Preliminary Results of a Prospective Study in 81 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4762-4762
Author(s):  
Marie-Pierre Gourin ◽  
Jacques Monteil ◽  
Benoit Marin ◽  
Stéphane Girault ◽  
Natalya Dmytruk ◽  
...  
Keyword(s):  
Prospective Study ◽  
Predictive Value ◽  
Complete Response ◽  
Therapeutic Outcome ◽  
Response To Treatment ◽  
High Grade ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mibi Scintigraphy

Abstract Abstract 4762 Introduction Tc-99m-MIBI, a radioactive tracer used in routine to explore myocardial perfusion, parathyroids or in oncology for high-grade glioma, has been described as a promising agent for the functional characterization of p-glyco-protein expression and the prediction of the therapeutic outcome in patients (pts) with Hodgkin (HL) and non-Hodgkin's lymphoma (NHL)( Liang LA, 2001; Kao CH 2002). As resistance to chemotherapy is the major cause of treatment failure in NHL, the goal of treatment is to avoid an incomplete response after first line chemotherapy. This prospective study was designed to investigate the relationship between uptake by Tc-99m-MIBI scintigraphy and response to treatment in aggressive and follicular NHL, and HL. Patients and Methods Study protocol was a monocentric prospective study conducted between 10/2005 and 11/2008. Inclusion criteria included untreated pts with a histological diagnosis of HL or high grade NHL or follicular (FL) and managed in a hematological regional care network: HEMATOLIM, aged 18 years and more, with an initial and final assessment by a CT scan and/or TEP scan and with an informed consent. Were excluded pregnant or lactating women, pts without social security coverage or with initial corticosteroids. During the initial assessment, a Tc-99m-MIBI was performed with an injection of 20 mCi of tracer before any therapeutics. Images were obtained 10 minutes after intra-venous injection of Tc-MIBI. The rate of complete response (CR) and incomplete response (IR) at the end of first line therapy was evaluated with and compared with MIBI uptake. Results The study included 81pts, sex ratio 1.61, median age 55 years (18-84)with an histological diagnosis of HL 41.9% (n=34), FL 9.9% (n=8), and aggressive NHL 48.2% (n=39) including DLBCL 38.3% (n=31), T cell NHL 4.9% (n=4), NK cell NHL 2.5% (n=2) and MCL 2.5% (n=2). Stade Ann Arbor I 6.2% (n=5), II 43.2% (n=35), III 12.3% (n=10) and IV 38.3% (n=31). Performans status were 0 for 51.85% (n=42), 1 for 35.8% (n=29), 2 for 11.11% (n=9) and 3 for 1.24% (n=1). LDH rate were increased 28.4% (n=23), normal 69.1% (n=56) and missing 2.5% (n=2). PSS for HL was favorable 41.18% (n=14), intermediate 47.06 (n=16) and unfavorable 11.76% (n=4). FLIPI score for FL was favorable 25% (n=2), intermediate for 62.5% (n=5) and non favorable for 12.5% (n=1). IPIa score was 0 for 29.03% (n=9), 1 for 32.26% (n=10), 2 for 19.35% (n=6) and 3 for 19.35% (n=6). All patients received chemotherapy in first line. For unfavorable pts a consolidation therapy has been added by radiotherapy 27.16% (n=22), or autologous stem cell transplantation for 8.54% (n=7). For 81 pts, MIBI results had positive uptake (MIBI+) 77.8% (n=63) and no uptake (MIBI-) 22.2% (n=18). For 75/81 pts eligible for final evaluation (6 deaths due to toxicity (n=3) or to NHL (n=3)), MIBI results showed 76% (n=57) MIBI+ and 24% (n=18) MIBI-. At the end of first line therapy, 82% of MIBI+ (n= 48/57) at diagnosis were in CR and 83% of MIBI – (15/18) were also in CR. There was no significant difference between the rate of MIBI+ and MIBI- for pts in CR by histological type. The distribution of disease localization were : thoracic (T) 59.3% (n=48), thoraco-abdominal (TA) 24.7% (n=20), abdominal (A) 13.6% (n=11), cranial 1.2% (n=1) and knee 1.2% (n=1). According to the results of MIBI, 83% of pts with a T localization were MIBI+ (n=40) versus 17% MIBI- (n=8), 70% of pts with a TA localization were MIBI+ (n=14) versus 30% MIBI- (n=6) and 63% of patients with a A localization were MIBI+ (n=7) versus 37% MIBI- (n=4). OS at 3 years is 90% and 3 years PFS is 79% with no significantly difference according to the response to MIBI. Sensitivity of MIBI is 80.77%, specificity 27.59%, positive predictive value is 66.67% and negative predictive value 44.44%. Conclusion This prospective study on 81 untreated pts with HL, and several varieties of aggressive NHL do not confirm the encouraging results previously reported by an asian study obtained on 25 pts considering Tc-99m as a useful predictive tool for chemoresistance. In our study, lack of MIBI uptake does not predict a decrease in the rate of complete response to treatment. Several explanations can be advanced: heterogeneous histology and prognostic score, small population. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Treatment patterns and overall survival in metastatic non-small-cell lung cancer in a real-world, US setting

2019 ◽  
Vol 15 (30) ◽  
pp. 3491-3502 ◽  
Author(s):  
Jason C Simeone ◽  
Beth L Nordstrom ◽  
Ketan Patel ◽  
Alyssa B Klein
Keyword(s):  
Lung Cancer ◽  
Treatment Patterns ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Metastatic Nsclc ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line

Aim: To conduct a retrospective analysis of electronic medical record data to understand real-world treatment patterns and overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC). Materials & methods: We included n = 9656 adults (≥18 years) with metastatic NSCLC and no prior therapy. Data from 1 January 2013 to 31 January 2017 were analyzed. Results: Carboplatin plus paclitaxel was the most common first-line therapy (18.6%), and nivolumab was the most common second- (31.0%) and third-line (38.4%) therapy; 26.7% of all patients were untreated. Median OS from initial metastatic diagnosis was 11.1 months (95% CI: 10.8–11.5). Second-line immunotherapy extended OS by over 3 months versus second-line chemotherapy. Conclusion: Platinum-based therapy was the most common first-line therapy, and immunotherapy was the most common second- and third-line therapy. Median OS of patients with metastatic NSCLC was <1 year.

scholarly journals Eltrombopag Plus Pulsed Dexamethasone As First Line Therapy for Subjects with Immune Thrombocytopenic Purpura (ITP)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 733-733 ◽  
Author(s):  
Lunqing Zhang ◽  
Mingjie Zhang ◽  
Xin Du ◽  
Yunfeng Cheng ◽  
Gregory Cheng
Keyword(s):  
Pilot Study ◽  
Response Rate ◽  
Response To Treatment ◽  
Platelet Response ◽  
First Line ◽  
Platelet Counts ◽  
First Line Therapy ◽  
Line Therapy ◽  
Prolonged Response

Abstract Background: Eltrombopag is an oral thrombopoietin receptor agonist that has been licensed for use as second line therapy in ITP patients. For most subjects, platelet counts usually return to baseline within 2 weeks of eltrombopag discontinuation, however, up to 15% of subjects may maintain a prolonged response after discontinuation (BJH Volume 165(6) 2014 865-869). Therefore, we conducted a pilot study to evaluate whether a 12-week course of eltrombopag plus pulsed dexamethasone as first line therapy can increase the proportion of patients with prolonged response. Methods: This multicenter, single arm, open-label pilot study was performed on subjects with newly diagnosed ITP. Eligible subjects had confirmed ITP and platelet counts <30×109/L or platelet counts < 50×109/L and significant bleeding symptoms (WHO bleeding scale 2 or above). Patients must have no prior ITP treatment except platelet transfusions. All patients provided written informed consent before enrolment. This study was conducted in accordance with the Declaration of Helsinki. Eligibility criteria included isolated thrombocytopenia with exclusions of secondary immune or drug-induced thrombocytopenia, cancer and pregnancy related thrombocytopenia and virus induced thrombocytopenia. Bone marrow examination is not mandatory but must be consistent with peripheral platelet consumptions with no features of dysplasia, extensive fibrosis, aplasia, marrow infiltration if performed. Treatment consisted of eltrombopag 25-75mg daily according to platelet response for 12 weeks plus pulsed dexamethasone, 40mg daily for 4 consecutive days every 4 weeks for 1-3 courses. The primary endpoint was prolonged response defined as platelet counts > 50×109/L for more than 6 months without any ITP therapy after completion of 12-week therapy. The reported prolonged response rate of dexamethasone alone is around 25%, a sample size of 60 subjects will be required to detect a doubling of the prolonged response rate at a significant level of 0.05 with power of 0.9. Differences between prolonged responder and relapsed subject groups were analyzed by the Student's t-test. P values <0.05 were considered significant. Results :46 subjects were enrolled from February 2015 to July 2018. The median age was 40 years, range 18 to 81; 29 were female and 17 were male. Median platelet counts at baseline were 18×109/L, range 1 to 44×109/L. One subject withdrew consent before starting treatment. One was withdrawn because of protocol violations. Three subjects did not have significant increase in platelet counts during the entire 12 weeks treatment despite a maximum of eltrombopag 75mg daily and 3 courses of pulsed dexamethasone. One of them subsequently turned out to be amegakaryocytic thrombocytopenia. These 5 subjects were still included in the final analysis. Twenty-nine subjects had good initial response to treatment and completed at least 6 months follow-up (Fig 1), 19 of them had achieved the primary end point of platelet counts count> 50×109/L for more than 6 months after discontinuation of eltrombopag. The median platelet counts at 6 months were 150×109/L (range 53 to 371×109/L), Average eltrombopag dose was 36.8mg daily and average pulsed dexamethasone was 2.2 courses. Eleven subjects maintained prolonged response for 12 months or more. Four subjects are still receiving treatment and 8 subjects are still on the 6 months off-therapy observation period (median follow up is 12 weeks, range 4 to 21 weeks). Ten subjects relapsed after discontinuation of eltrombopag(Table 1). The median time to relapse was 47.8 days, range 15 to 148 days. Average daily eltrombopag was 45mg and average pulsed dexamethasone was 2.5 courses. So far, the prolonged response rate of 56 % (19/34) among 34 evaluable subjects is very encouraging. According to statistical analysis, seven more prolonged responders among the remaining 26 subjects (14 yet enrolled and 12 pending final evaluation) would suggest that 12-week of eltrombopag plus pulsed dexamethasone as first line therapy may significantly improve prolonged response rate in ITP patients. All subjects tolerated the treatment well and no Grade 3 or above adverse effects were reported. Conclusions: Eltrombopag plus pulsed dexamethasone is an effective and safe treatment for ITP as a first line therapy that can provide sustained prolonged response in adults. This therapy could be a new treatment option for ITP subjects. Disclosures Cheng: Novartis: Research Funding; BMS: Honoraria, Speakers Bureau; Astrazeneca: Honoraria, Speakers Bureau.

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