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

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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Primary Female Genital Lymphoma: Prognostic and Therapeutic Considerations

Blood ◽

10.1182/blood.v112.11.4941.4941 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4941-4941

Author(s):

Sara Steffanoni ◽

Alberto Agazzi ◽

Daniele Laszlo ◽

Sarah Jane Liptrott ◽

Mara Negri ◽

...

Keyword(s):

Response Rate ◽

Early Stage ◽

Local Treatment ◽

High Dose ◽

First Line ◽

Bulky Disease ◽

First Line Therapy ◽

Line Therapy ◽

Female Genital

Abstract Primary Female Genital Lymphoma (PFGL) is very rare, representing 1.5% of all Non-Hodgkin’s Lymphomas (NHLs) and 0.5% of female genital malignant tumours; uterus is the main commonly genital site involved by NHL. Most PFGLs are B-cell lymphomas; usually they occur in 5th decade of life. Because of PFGL rarity, a standard treatment has not been identified yet. This is a retrospective study on 20 women with PFGL, treated at European Institute of Oncology. The median age was 52 yrs (range 30–79 yrs); at diagnosis 6 pts were asymptomatic, 11 reported pelvic symptoms and 3 B symptoms. According to the International Prognostic Index, 7 pts had low, 6 intermediate, 6 high risk and one pt not known. Eleven pts had uterine involvement, with a concomitant extension to vagina in 5 of them, ovary NHL was recognised in 4 pts, vaginal NHL in 4 pts and vulvar NHL in one pt. Diffuse large B-cell NHL (DLBCL) was diagnosed in 14 pts, marginal extranodal NHL in 3 pts and follicular in 3 pts. According to Ann Arbor staging system: 8 pts were in early stage (IE–IIE) and 12 pts in stage IVE; considering FIGO system: 11 pts were in early stage (I–II), 6 pts in stage III for regional lymph node involvement and 3 in stage IV for concomitant non-genital extranodal localization; 12 pts presented with bulky disease. At diagnosis no pts had bone marrow involvement. The diagnostic biopsy was performed by endoscopy in 13 pts and by ultrasound-guided in 2 pts, whereas 5 pts underwent laparotomy. One pt with vulva-limited marginal NHL did not receive any treatment until disease progression (PD) and transformation to DLBCL. Five pts underwent laparotomy and adjuvant chemotherapy (CT) alone (n=4) or in combination with radiotherapy (RT) (n=1); 14 pts received CT alone (n=8) or in combination with RT (n=6) as first line therapy. Anthracycline-containing CT was delivered to all pts with DLBCL (n=14) and to one pt with high grade follicular NHL, 12 of them received concurrent immunotherapy anti-CD20 (Rituximab). Central nervous system (CNS) chemo-prophylaxis with i.v. high dose methotrexate was delivered to 3 pts because of advanced or bulky disease. Two pts with follicular and 2 with marginal subtype received alkylating-containing CT alone (n=2) or with Rituximab (n=2). The Overall Response Rate (ORR) to first line therapy was 80%; the response did not improve by the addition of local treatment to CT. Three pts did not response to first line therapy: one with marginal NHL in stable disease did not receive any additional treatment because of asymptomatic disease; two with DLBCL in PD underwent salvage treatment with high dose CT and died in PD, concurrent intrathecal therapy was mandatory in one pt because of CNS relapse. Three pts with follicular NHL, in response to first line therapy, relapsed: one went on to receive maintenance Rituximab, one resulted refractory to different rescue CT regimens and died in PD, one underwent autologous bone marrow transplantation obtaining CR. After a median follow up of 51 months (range 11–164 months), 17 pts are still alive: 10 in CR and 7 in PR, 3 pts died in PD. The Overall Survival (OS) at 3 and 14 yrs was 84.8% and 42.4% respectively. According to the literature the most common histological subtype of PFGL occurred in our population was DLBCL and the most frequent genital site involved was uterus (55% of cases) [Lagoo et al. 2006]. An additional local treatment did not seem to give an advantage in terms of ORR, PFS and OS in comparison with systemic therapy alone, as stated by the literature [Signorelli et al. 2006]. Concerning the pts treated with anthracycline-containing CT with or without Rituximab (n=15), 8 pts (53%) and 5 pts (33%) achieved CR and PR respectively, 2 pts (13%) had a PD during treatment, only one pt in CR relapsed after 65 months from the first line therapy. After a median follow up of 27 months 12 pts (80%) are alive, 3 (20%) died in PD. The Response Rate and OS in the subgroup of pts that received anthracycline-containing CT resulted similar to those reported in the literature [Coiffier 2002]; therefore female genital involvement by NHL doesn’t seem to represent a negative prognostic factor.

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Greek Registry Of Essential Thrombocythemia: Baseline Characteristics and Therapeutic Strategy

Blood ◽

10.1182/blood.v122.21.4084.4084 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4084-4084

Author(s):

Damianos Sotiropoulos ◽

Argiris Symeonidis ◽

Vassilios K Papadopoulos ◽

Panagiotis Tsirigotis ◽

Maria Pagoni ◽

...

Keyword(s):

Risk Factor ◽

Significant Risk ◽

Jak2 V617f ◽

Significant Risk Factor ◽

First Line ◽

Platelet Counts ◽

First Line Therapy ◽

Line Therapy ◽

History Of

Abstract The Greek Registry of Essential Thrombocythemia (ET) is implemented under the auspices of the Acute Leukemias and Myeloproliferative Neoplasms Study Group of the Hellenic Society of Haematology. Hereby, we present results after four years of retrospective data collection. The total number of patients included is 1078, from 14 Greek sites; ET was diagnosed between 1982 and 2012. The male to female ratio is 1:1.19. Median age at diagnosis is 63 years, median platelet counts (PLT) 826x109/L, hemoglobin (Hb) 13.6 g/dL, white blood cell counts (WBC) 9.4x109/L. The presenting symptoms were a thrombotic event in 6.8%, a hemorrhagic event in 1.5% of patients. In 79.8% of the patients the diagnosis was made after incidental finding of elevated platelet counts on routine laboratory investigation. Molecular studies were performed in 677 patients and 42.8% of them were positive for the JAK2-V617F mutation. The presence of JAK2-V617F mutation (mutant vs wild type allele) was associated with baseline platelet counts (757.5 vs 882 x109/L) and hemoglobin levels (14.4 vs 13.4 g/dL), p<0.001 (Mann-Whitney U-test). A history of thrombosis or hemorrhage was present in 18.6% and 6.6% of patients respectively. Chi-square test was performed to assess whether platelet counts at diagnosis (<600, 600-800, >800 x109/L), Hb<13.8g/dL, WBC>9.5x109/L, or splenomegaly are associated with thrombotic or hemorrhagic events in the past medical history or during the follow-up of ET patients. The only statistically significant difference was observed in the occurrence of thrombosis during the follow up: 10.1% of those with PLT between 600-800 x109/L, 4.5% in PLT<600 and 5.6% in PLT>800 x109/L. To assess for possible confounders the multivariable logistic regression model was used, with independent variables the PLT at diagnosis, age >60 years, history of thrombosis and first line therapy. The history of thrombosis was the only statistically significant risk factor with odds ratio (OR) 3.9 (p=0.0005), while PLT was not a statistically significant risk factor (OR=2.5, p=0.074). Antiplatelet therapy was offered in 80% of patients (aspirin in 59.1%, clopidogrel in 4.7%, and combination therapy in 6.5%); anticoagulants (low molecular weight heparin or warfarin) were given in 2.3%, while the remaining 17.8% of patients did not receive any antithrombotic therapy. During the first six months post diagnosis, 31.6% of patients did not need any cytoreductive therapy. The rest 68.4% of the patients received first line therapy (hydroxyurea 80.6%, anagrelide 11.4% and interferon 5.4%). The response rates were 89.9%, 82.1% and 85.7%, respectively. Second-line therapy was received by 25.8% of the patients (hydroxyurea 23%, anagrelide 44.6%, interferon 9.5%), while the off-label combination of hydroxyurea and anagrelide was administered to 21.2% of the patients. Of the 852 patients treated with hydroxyurea as first line therapy, 12.1% switched to anagrelide and 1.2% to interferon. Of those initially treated with anagrelide, 27.6% switched to hydroxyurea and 8.2% to interferon. During the follow up phase, secondary solid tumor occurred in 4% and hematological malignancy in 2.7% of the patients. The aim of the registry and the subsequent data analysis is to convey the practice of managing the disease. Moreover, useful conclusions can be reached regarding to the patients’ responsiveness to therapy and the minimization of thrombotic and hemorrhagic adverse events. Disclosures: Spanoudakis: Genesis Hellas: Honoraria. Kotsianidis:Genesis Hellas: Honoraria, Research Funding.

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Impact of Rituximab in the Clinical Outcomes of Hairy Cell Leukemia: A Retrospective Single-Institution Analysis

Blood ◽

10.1182/blood-2019-129028 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1542-1542

Author(s):

Kristen Gonter-Aubin ◽

Daniel Alan Kerr ◽

Ashley Rose ◽

Thanh Lana Nguyen ◽

Julio C. Chavez ◽

...

Keyword(s):

Board Of Directors ◽

Response Rate ◽

Hairy Cell ◽

Single Institution ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy

Background: Hairy cell leukemia (HCL) is an indolent mature B-cell disorder that comprises ~2% of all leukemias. Purine nucleoside analogues (PNA) such as cladribine and pentostatin remain the standard initial treatment with high response rate, however frequent late relapses occur. The addition of rituximab (R) has shown efficacy as a single agent and in combination in the first- and second-line settings . Recent data suggests that the addition of R to PNA increased the minimal residual disease (MRD) negative (neg) and duration of response (DOR) when compared to PNA alone. In this study, we examined the impact of rituximab (R) in the long term outcomes of HCL from a single institution experience. Methods: An IRB-approved retrospective analysis was performed including patients with HCL or HCL-variant who were seen at Moffitt Cancer Center between 1/2000 and 2/ 2019. Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints included overall response rate (ORR). Complete Remission (CR) was determined based off of accepted criteria of Hgb > 11gr/dL, platelets > 100,000/µL and ANC > 1500/µL. Statistical comparisons and survival analyses were performed using SPSSTM Statistics and GraphPad PrismTM. Results: We identified 124 cases with available treatment data and follow up (82 HCL, 15 CD25-negative HCLv). The median follow-up was 72 months. The median age was 57 years (27 - 89+). The 5 and 10 year OS was 97% and 91%, respectively, with 2 deaths reported secondary to HCL or complications from HCL. The median PFS for all patients receiving first-line therapy was 92 months. Clinical risk factors present at diagnosis that were independently associated with worse PFS after first-line therapy were weight loss (HR 2.27, p = 0.057), recurrent infections (HR 2.50, p=0.009) and splenomegaly (HR 1.87, p=0.047),, hemoglobin less than 11 gr/dL (HR 3.12, p=0.016), and negative CD25 (HR 2.14, p=0.055). In multivariate analyses, negative CD25, recurrent infections and Hgb < 11 gr/dL were associated with worse PFS after first line therapy (p = 0.002). Most patients received PNA alone or PNA+R (96 and 18, respectively) as first line with a higher CR rate in the PNA+R group (100% vs 71%) and a higher median PFS for [not reached (NR) and 82 months, respectively, p = 0.165] with 2 relapses in the PNA+R group (both at 30 months). In the 2nd line setting, PNA+R (n = 11) was also associated with a higher CR rate than PNA alone (n = 22, 82% vs 64%) with only 1 relapse in the PNA+R group at 97 months. The median PFS for 2nd line PNA+R vs 2-CdA was 97 and 43 months, respectively (p = 0.253). Conclusions: In this study, we report a large, retrospective, single-institution dataset of HCL and HCLv patients with long-term follow-up. The addition of R may improve the PFS in patients with HCL in the first and 2nd -line settings however a longer follow up is needed. A recently described prospective randomized trial in the use of concomitant rituximab plus PNA has reported a higher MRD free CR in comparison with PNA alone but not PFS yet. Disclosures Chavez: Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees. Pinilla Ibarz:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy; TG Therapeutics: Consultancy; Bayer: Speakers Bureau; Sanofi: Speakers Bureau.

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In Multiple Myeloma Progression Free and Overall Survival in the Relapsed Setting Remains Poor with Early Exposure to Novel Agents: Experience from a Real-World Cohort

Blood ◽

10.1182/blood.v126.23.4261.4261 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4261-4261 ◽

Cited By ~ 1

Author(s):

Christopher P. Venner ◽

Nizar J Bahlis ◽

Paola Neri ◽

Irwindeep Sandhu ◽

Peter Duggan ◽

...

Keyword(s):

Research Funding ◽

Response Rate ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Third Line Therapy ◽

First Relapse ◽

Third Line ◽

Line Of Therapy

Abstract Introduction: With the widespread adoption of novel agents (NA) in all lines of therapy patients are being exposed to both proteosome inhibitors (PIs) and immunomodulatory drugs (IMiDs) early in their treatment course. This has lead to marked improvements in survival in the frontline setting. Data is limited with respect to patient outcomes after exposure to both these drug classes in the real world setting. Here we present our experience examining outcomes after each line of therapy whereby bortezomib-based induction followed by lenalidomide-based therapy at first relapse has become the standard of care. We further explored the outcomes of patients who were exposed to both active classes of drugs within their first 2 lines of therapy. Patients and methods: This series includes patients seen through the provincial Alberta Myeloma and Dysproteinemia Program in Canada. Only patients treated between 2005-2013 were included to allow at least 2 years of follow-up beyond first line therapy. Only those treated with a NA-containing regimen as part of their first line treatment were examined. The cohort was split based on eligibility for autologous stem cell transplant (ASCT). Double exposed patients were those who had been treated with, but were not necessarily refractory to both an IMiD and PI within the first 2 lines of treatment. Outcomes were measured after first, second and third line therapy. Survival outcomes were measured in months (m). OS was measured from the start of each line of therapy until death or last follow-up. PFS was from the start of each line of therapy to relapse, death or last follow-up. Response was measured as per the most recent International Myeloma Working Group criteria. Near complete response (nCR) was used when the monoclonal protein disappeared on protein electrophoresis but was not confirmed by immunofixation. Results: Two hundred forty eight patients had received upfront therapy (non-ASCT = 113 and ASCT = 135). One hundred twenty seven had received second line therapy (non-ASCT = 62 and ASCT = 65). Sixty-four had received third line therapy (non-ASCT = 31 and ASCT = 33). The median OS and PFS after each line of therapy are shown in table 1. After first line therapy the OS (p < 0.001) and PFS (p< 0.001) were significantly better in the ASCT cohort. There were no significant differences in survival outcomes based on transplant eligibility in subsequent lines of therapy (figure 1A and B). The overall response rate to third line therapy was 45% (VGPR = 14% and nCR = 7%) for non-ASCT patients and 52% (VGPR = 15% and nCR = 6%) for ASCT patients. Fifty-five percent of non-ASCT patients failed to respond during third line therapy (34% with progressive (PD) and 21% with stable disease (SD)). Forty-eight percent of ASCT patients failed to respond (PD = 27% and SD = 21%). Forty-seven patients were double exposed within the first 2 lines of therapy (non-ASCT = 26 and ASCT = 21). In this cohort, the OS and PFS after double exposure (i.e. third line therapy) was 15m and 5m respectively with no significant difference based transplant eligibility (figure 1C and D). The response rate to third line therapy was 46% (VGPR = 17% and nCR = 8%) for ASCT patients and 43% (VGPR = 14% and nCR = 5%) for non-ASCT patients. Fifty-five percent failed to respond (PD = 38% and SD = 17%) in the non-ASCT group. Fifty-seven percent failed to respond (PD = 38% and SD = 19%) in the ASCT group. Summary: The introduction of NAs earlier in the management of patients with myeloma has improved OS. This is driven by improvements in PFS to frontline therapy and after first relapse. However, with current therapeutic approaches patients will be exposed to both IMiDs and PIs much earlier in their disease. In many jurisdictions, the limited treatment options in third line and beyond, especially in double exposed patients, poses a significant therapeutic challenge. Durable responses are limited in this setting with most patients relapsing after only 6 months. In addition, approximately a third of patients have overtly progressive disease. Interestingly, front-line ASCT eligibility had no impact on outcome with subsequent relapses, emphasizing the fact that ASCT only improves the outcome for the line in which it is employed. Further study regarding resistant mechanism and clonal evolution after exposure to both IMiDs and PIs will be important in developing rationally designed therapeutic regimens for this population. Disclosures Venner: J&J: Honoraria, Research Funding; Amgen: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: Some patients in this series will have received frontline lenalidomide which is not yet an approved indication for this drug in Canada.. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Johnson & Johnson: Research Funding. Neri:Celgene: Research Funding. Sandhu:Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Belch:Janssen-Cilag: Consultancy. Jimenez-Zepeda:Celgene: Honoraria; J&J: Honoraria; Amgen: Honoraria.

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A Phase II Study of Bortezomib (Velcade ®), Cyclophosphamide (Cytoxan®), Thalidomide (Thalomid®) and Dexamethasone as First-Line Therapy for Multiple Myeloma

Blood ◽

10.1182/blood.v112.11.94.94 ◽

2008 ◽

Vol 112 (11) ◽

pp. 94-94 ◽

Cited By ~ 6

Author(s):

William Bensinger ◽

Sundar Jagannath ◽

Robert Vescio ◽

Elber S. Camacho ◽

Jeffrey Lee Wolf ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Phase Ii ◽

Induction Therapy ◽

Response Rate ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Cell Harvest

Abstract Background: This phase II trial evaluated the response rate of sequential bortezomib (VELCADE®), cyclophosphamide (Cytoxan®), and dexamethasone ([VCD]; 3 cycles) followed by bortezomib, thalidomide (Thalomid®), and dexamethasone ([VTD]; 3 cycles) as first-line therapy for patients with multiple myeloma. The primary endpoints were overall response, achievement of „d very good partial response (VGPR), as well as assessment of safety and tolerability. Methods: Patients with newly diagnosed, untreated symptomatic myeloma were eligible. Treatment consisted of three 21-day cycles of bortezomib 1.3mg/m2 days 1, 4, 8, and 11, cyclophosphamide 300mg/m2 IV days 1 and 8 and dexamethasone 40mg p.o. or IV days 1, 2, 4, 5, 8, 9, 11, 12; followed by three 21-day cycles of bortezomib 1.0mg/m2 days 1, 4, 8, and 11; thalidomide 100 mg p.o. daily and dexamethasone same as cycles 1–3. Patients received thrombosis prophylaxis with ASA 325mg daily during cycles 4–6. Upon completion of the 6 cycles, patients proceeded to autologous stem cell harvest, transplant and/or maintenance therapy. Responses were defined as a decrease in serum and/or urine monoclonal (M) protein by 50% or greater. VGPR and other responses were as per the International Response Criteria. Results: This report provides results for all 44 eligible patients: median age 59 years; 68% male; 61% Stage III (D/S); documented ISS Stage II/III 59%; IgG 66%, IgA 17%; 17% light chain only. To date the first 30 patients are fully evaluable for response with 28-day post therapy follow up. The overall response rate (ORR; ≥PR) is 90% with 18/30 (60%) achieving CR + VGPR (CR 33%); 9/30 (30%) PR and 3/30 (10%) stable disease or not evaluable. Overall, both components of the sequential regimen were very well tolerated. One patient had a ruptured colonic diverticulum possibly related to dexamethasone, but recovered well and achieved VGPR on trial. There have been 49 therapy attributed toxicity events which have required drug/schedule adjustments. Of these, 9 events were Gd 3/4: 3 attributed to cyclophosphamide, 3 to dexamethasone, 2 attributed to bortezomib and 1 to thalidomide. DVT occurred in one patient who was at high risk because of prior bilateral hip surgery. Fourteen patients have proceeded to successful stem cell harvest and autologous transplant. Post transplant follow up as well as response information for all 44 patients will be presented. Conclusion: This bortezomib/cyclophosphamide/dexamethasone (VCD) based combination induction therapy followed by VTD is a promising addition to the treatment armamentarium for previously untreated patients. The response rates: ORR 90%; □ VGPR (60%) and CR (33%) are extremely encouraging and improve over our bortezomib/dexamethasone 2-drug experience which produced 90% □ PR and 38% □ VGPR. This very well tolerated new regimen is potentially an important step forward in induction therapy with presentation of more mature data. Supported by the Aptium Oncology Research Network and a research grant from Millennium Pharmaceuticals, Inc.

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Evaluation in the Context of Daily Practice of Follicular Lymphoma patients' Outcome Before and After Approval of Rituximab in First Line Therapy in This Indication: Results of a Retrospective Analysis of 247 Unselected Patients with a 5-Year Median of Follow-up,

Blood ◽

10.1182/blood.v118.21.3698.3698 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3698-3698

Author(s):

Emmanuelle Nicolas Virelizier ◽

Celine Segura-Ferlay ◽

Izabela-Irina Domnisoru ◽

Philippe Rey ◽

Thérèse Gargi ◽

...

Keyword(s):

Clinical Trials ◽

Follicular Lymphoma ◽

Retrospective Analysis ◽

Response Rate ◽

Daily Practice ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Before And After

Abstract Abstract 3698 Background: Randomized trials had demonstrated that rituximab improved outcome in newly diagnosed follicular lymphoma (FL) and this anti-CD20 monoclonal antibody was approved in France since 2004 in combination of chemotherapy (CT) for LF in first line therapy. As these results were obtained in selected patients with strict inclusion and exclusion criteria used in clinical trials, whether the improvement of patient's outcome is valuable in unselected population of FL patients with various medical history, different CT regimens is questionable. We performed a retrospective analysis to evaluate if the management and the outcome of FL have significantly changed in our institution before and after rituximab approval in 2004. Patients and Methods: all adult patients referred for first line LF were included and separated into cohort 1 diagnosis between 1996 and 2003 (103 patients) and cohort 2 between 2004 and 2010 (144 patients). Baseline clinical and biological datas, Follicular Lymphoma International prognostic Index (FLIPI), type of therapy, treatment response, progression free survival (PFS) and overall survival (OS) were compared. Results: There were no statistical differences in patients' characteristics between the 2 cohorts, including FLIPI score. In cohort 2, 71% received in first line therapy a rituximab based regimen (19% in monotherapy and 52% with CT). In cohort 1, 58% of patients were treated with CT and 10% with rituximab, 2% in monotherapy and 8% in combination with CT. Response rate were significantly improved in cohort 2 compared to cohort 1: complete response rate was 74.3% versus 57.8%, P <.001. With a median follow-up of 115.5 and 46.5 months in cohort 1 and 2, the 2-year PFS was 67% for cohort 1 and 82% for cohort 2 (P =.0039), respectively. The 2-year OS was also improved between the two periods (98% versus 87%, P =.0007). We could confirm the prognostic value on OS of the FLIPI score in whole series, in cohort 1 before the rituximab era but not in cohort 2. In fact, the 2-year OS was respectively 100% in low risk, 98% in intermediate risk and 95% in high risk (P =.14)/ Conclusions: These datas confirms the improvement of FL patients' outcome observed in clinical trials after the approval of rituximab in first line therapy prescript in a context of daily practice whatever age, medical history, and type of CT. Disclosures: No relevant conflicts of interest to declare.

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GCT-28. RECURRENCE PATTERN AND SURVIVAL FOR RELAPSED INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A SINGLE-INSTITUTION EXPERIENCE

Neuro-Oncology ◽

10.1093/neuonc/noaa222.248 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii333-iii333

Author(s):

Lei Wen ◽

Zhaoming Zhou ◽

Qingjun Hu ◽

Juan Li ◽

Mingyao Lai ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Late Recurrence ◽

Salvage Chemotherapy ◽

Recurrence Time ◽

First Line ◽

Primary Tumor Site ◽

First Line Therapy ◽

Line Therapy

Abstract PURPOSE Intracranial non-germinomatous germ cell tumors (NGGCTs) have lower overall survival than germinoma because relatively higher recurrence usually occurs after first line therapy. METHODS Between January 2003 and December 2018, 111 consecutive patients diagnosed with NGGCTs reviewed. Those who progressed after first line therapy were included in this study. Data of first line treatment, salvage treatment, clinicopathological features and survival were collected and analyzed. RESULTS Totally, thirty patients (30/111, 27.0%) relapsed in our cohort, including 19 patients with accurate relapse information detail, and 11 patients who died of disease progression during follow up but without exact time and site of relapse. The median OS from diagnosis of the disease was 49.2 months (95% CI: 14.1 to 84.3 months) and 3-year OS was 54.3%. Patients who received both CSI and chemotherapy relapsed less than those who received reduced volume of radiotherapy or only CSI or only chemotherapy (22.5% vs. 45.5%, p=0.034). Of 19 patients who had detail information of recurrence time and site, the median time from diagnosis of disease to relapse was 9.5 months (2.2 to 72.1 months). Regarding to recurrence site, most patients relapsed in primary site (10/19, 52.6%) or distant intracranial (6/19, 31.6%). The recurrence site of other 3 patients were spinal (n=1), ventricular (n=1) and peritoneal (n=1). CONCLUSION Protracted follow-up is recommended because late recurrence is not uncommon. Primary tumor site and distant intracranial are the most prevalent relapsed location. Patients who relapsed could benefited from both CSI and salvage chemotherapy.

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A Female with Evans Syndrome Presented with Pancytopenia

Journal of Enam Medical College ◽

10.3329/jemc.v10i2.53537 ◽

2021 ◽

Vol 10 (2) ◽

pp. 114-117

Author(s):

Md Rezaul Karim Chowdhury ◽

Md Haroon Ur Rashid ◽

Md Mahbub Hossain ◽

Shafayet Hossain Riyan

Keyword(s):

Oral Prednisolone ◽

Low Grade ◽

Evans Syndrome ◽

First Line ◽

Indirect Bilirubin ◽

First Line Therapy ◽

Line Therapy ◽

Immune Neutropenia ◽

Chronic Course

Evans syndrome is an uncommon haematological disorder characterised by autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and/or immune neutropenia. It may occur in all ethnic groups, all ages and has no sex predilection. The direct antiglobulin test (DAT) is almost invariably positive. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. Corticosteroids and/or intravenous immunoglobulin (IVIG) are the most commonly used first line therapy. Here we report a case of a female who presented with severe shortness of breath, palpitation and low grade fever and on examination she was found severely pale and mildly icteric. Her CBC and PBF showed pancytopenia. Indirect bilirubin and LDH were raised and direct Coomb’s test was positive. She was labeled as a case of Evans syndrome and responded to oral prednisolone. On subsequent follow-up her haematological profiles remained normal. J Enam Med Col 2020; 10(2): 114-117

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