ALBERT

Description: Background: The trombopoietin receptor agonists (TRAs) romiplostim and eltrombopag are effective and safe in the treatment of chronic immune thrombocytopenia (ITP). However, when no response is achieved or when adverse events occur with one TRA the value of the sequential use of romiplostim and eltrombopag has not been clearly established. Here we have evaluated the efficacy and tolerance of using eltrombopag after romiplostim in ITP. Methods: Fifty-one primary ITP patients (aged 18 years or more) who had been sequentially treated first with romiplostim and then with eltrombopag in the Spanish Eltrombopag Registry were retrospectively evaluated. In accordance with the usual standards, complete response was defined as a platelet count of 100x109/L and a response as a platelet count of 30x109/L or a count of at least twice the initial (pre-treatment) value. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age of our cohort was 49 [range, 18–83] years. There were 32 women and 19 men. According to the standard definition, patients were allocated to newly diagnosed (n=2), persistent (n=5) and chronic (n=44) ITP groups. The median number of therapies prior to administration of eltrombopag was 4 [range, 2–9], including splenectomy (39%), rituximab (33%) and romiplostim (100%). The median duration of romiplostim use before switching to eltrombopag was 12 (IQR 5–21) months. The reasons for switching from the romiplostim to eltrombopag were: lack of efficacy of romiplostim (n=25), patient's preference (n=16), platelet-count fluctuation (n=6), and side-effects (n=4). The initial response rate to eltrombopag was 41/51 (80.5%), including 67% (n=34) of cases with complete remission. After a median follow-up of 13 months with eltrombopag, 39 patients maintained their response. When eltrombopag was used for patients who were refractory to the maximum romiplostim dose the initial response rate of eltrombopag was 25%. However, 83% of patients who relapsed after their initial response to romiplostim responded to eltrombopag. Sixteen romiplostim responders requested their physicians to switch them to eltrombopag because they preferred an oral drug. The efficacy was maintained after switching in all 16 patients. In the platelet-count fluctuation group, the initial response rate was also 100%. All 4 patients who were switched to eltrombopag because they experienced side-effects of romiplostim achieved complete remission with eltrombopag and their adverse events were resolved. 16 / 51 (33%) patients experienced one or more adverse event during treatment with eltrombopag. The frequency of grade 3–4 adverse events during treatment with eltrombopag was 9.8%. Conclusion: The use of eltrombopag after romiplostim for treating ITP is effective and safe. The reason for discontinuing romiplostim was associated with the response to eltrombopag. Disclosures No relevant conflicts of interest to declare.

Description: Management of immune thrombocytopenia (ITP) during pregnancy can be challenging since treatment choices are limited. Thrombopoietin receptor agonists (Tpo-RAs), which likely cross the placenta, are not recommended during pregnancy. To better assess safety and efficacy of off-label use of Tpo-RA during pregnancy, a multicenter observational and retrospective study was set up. Results from 15 pregnant women with ITP (17 pregnancies and 18 neonates) treated with either eltrombopag (N=8) or romiplostim (n=7) during pregnancy, including 2 patients with secondary ITP, were analyzed. Median time of Tpo-RA exposure during pregnancy was 4.4 weeks [range: 1-39 weeks]; the indication for starting Tpo-RA was preparation for delivery in 10/17 (58%) pregnancies whereas 4 had chronic refractory symptomatic ITP and 3 were on eltrombopag when the pregnancy started. Regarding safety, neither thromboembolic events among mothers nor Tpo-RA-related fetal or neonatal complications were observed except for one case of neonatal thrombocytosis. Response to Tpo-RA was achieved in 77% of cases, mostly in combination (70% of responders) with concomitant ITP therapy. Based on these preliminary findings, temporary off-label use of a Tpo-RA for severe and/or refractory ITP during pregnancy seems safe for both mother and neonate and likely to be helpful especially prior to delivery.

Description: Background: Eltrombopag is an oral thrombopoietin receptor agonist (TPO-RA) drug approved in primary chronic ITP. Lack of clinical trials in secondary ITP avoids a clear demonstration of its potential in terms of safety and efficacy on secondary ITP. Aims: To evaluate the efficacy and safety of eltrombopag in secondary ITP patients in daily clinical practice in Spain. Methods: Ninety-eight secondary ITP patients (aged 18 years or more) from 30 Spanish centers, treated with eltrombopag and included in the Spanish Eltrombopag Registry were retrospectively evaluated. Our study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: Our case series included 98 patients we allocated to four categories: immune disorders (n=47), infections (n=23), lymphoproliferative disorders (n=20), and neoplasms (n=8). The median age of the cohort was 62 (IQR, 40-71) years with 38 men and 60 women. At diagnosis, 34 patients had a Charlson Comorbidity Index score of 2 or more. Median time from ITP diagnosis to eltrombopag initiation was 13 (IQR, 2-66) months. Median number of therapies against thrombocytopenia before eltrombopag was 2 (IQR, 1-3), including rituximab (24), splenectomy (18) and romiplostim (13). Median platelet count when treatment started was 15 x 109/L (IQR, 5-43 x 109/L). Meanwhile, 44 patients had bleeding symptoms. Concomitant therapy was administered to 55 ITP (corticoids in 33) (Table I). Whole cohort eltrombopag response rate was 59% of responses (R; platelet count ≥30 x109/L and at least 2-fold increase the baseline count and absence of bleeding) with 52% of complete responses (CR; platelet count 〉100 x 109/L). Regarding the disease associated to ITP we observed high response rates in immune disorders and infection groups (67% of R, 76 % of R, respectively). Nevertheless, in lymphoproliferative disorders and neoplastic groups efficacy rates were much lower (36 % of R, 37 % of R respectively). The proportion of patients achieving platelet response was quite similar regardless the other studied parameters: age, sex, concomitant treatment, bleeding and platelet count at start of eltrombopag treatment. 30 adverse events were reported with eltrombopag, being 18 of them grade 3-4. 14 deaths were observed but only two were caused by bleeding. The remaining causes of death were: 4 because of bacterial sepsis and another 4 due to progression of basal disease. 2 secondary neoplasms, 1 aspergillosis and one death due to a non-treated severe anemia were also reported (Table II). Conclusion: The use of eltrombopag for treating secondary ITP is effective and safe. To point out, its efficacy in lymphoproliferative disorders and in neoplasm-associated ITP is lower than in benign diseases. Certainly, more studies are needed to confirm usefulness of TPO-RAs in secondary ITP cases. Table 1. Patient characteristics Variable Total(n = 98) Type of disease, n Immune disorders  SLE 13  Evans Syndrome 8  Antiphospholipid Syndrome 6  Sjögren Syndrome 5  Rheumatoid Arthritis 3  Immunodeficiencies 3  Autoimmune Hepatitis 2  Primary Biliary Cirrhosis 2  Psoriatic arthritis 1  Evans Syndrome-Immunodeficiencies 1  Evans Syndrome-HCV 1  Graves-Basedow disease 1  Inflammatory Bowel disease 1 Lymphoproliferative disorders  Lymphoproliferative diseases 16  HCV-Lymphoma 3  HIV-Lymphoma 1 Infections  Hepatitis C Virus 16  HIV 5  HCV-HIV 2 Neoplasms  Myeloid Neoplasms 8 Age, years, median [Q1;Q3] 62[40;71] Men/Women n 38/60 Bleeding at start of eltrombopag treatment, n 44 Concomitant treatment, n 55  Corticoids 33  Immunoglobulins 6  Corticoids and Immunoglobulins 7 Table 2. Adverse events with Eltrombopag Variable n Total, n 30 Serious Adverse Events (Grade 3-4), n 18  Progression of basal disease 4  Severe Bacterial Infections 3  Deep venous thrombosis 3  Stroke 2  Medullary fibrosis 2  Severe Bleeding 1  Aspergillosis 1  Pulmonary Embolism 1  Secondary neoplasms 1  Acute Pancreatitis 1  Acute Myocardial Infarction 1 Deaths, n 14  Bacterial Infections 4  Progression of basal disease 4  Secondary neoplasms 2  Severe Bleeding 2  Aspergillosis 1   Severe Anemia due to negative of patient to transfusion 1 Disclosures Off Label Use: We describe the possibility of using eltrombopag, an oral thrombopoietin receptor analog, for secondary ITP patients..

Description: Abstract 4942 INTRODUCTION. Patients with Mantle cell lymphoma (MCL) have an adverse outcome after relapse due to chemorefractory disease with conventional treatments. Bendamustine, a nitrogen mustard compound chemically related to the alkylating agents, has demonstrated high efficacy with a low toxicity profile in reported clinical trials. AIM. To analyze the Spanish experience in patients with relapsed/refractory MCL treated with Bendamustine. METHODS. Retrospective analysis of spanish experience in relapsed/refractory MCL treated with Bendamustine alone or in combination. This study has been approved by local ethical committees. RESULTS. Currently, there are 36 patients registered and 28 are available for this analysis. Patients'characteristics: 69% male, median age 65 years old (range 41–81), 87% ECOG≤ 1, 83% Ann Arbor stage IV, 37% high risk MIPI and 9% blastic variant. Previous regimens were CHOP or CHOP like ± R in 42.5%, HyperCVAD/MtxAraC ± R in 42.5%, R-CVP in 9% and other regimens in 6%. Median number of previous treatments were 2.6 (range 1–6), all patients had received prior Rituximab and 73% had chemosensitive disease to the last treatment. Bendamustine regimen was R-B (R-375mg/m2 D1, B-90 mg/m2 D1-2) in 78% patients, R-B with B-70 mg/m2 in 8%, B alone in 3%, R-B-Bortezomib in 3% and R-B plus consolidation (SCT, Y90Ibritumomab-tiuxetan) in 8%. Median number of cycles was 4.61 (range 1–7). G- CSF support was administered in 43% of cycles. Response: Overall response rate was 73%, with 43% CR & uCR and 30% PR. Survival: Median overall survival from diagnosis is 8,26 years (range: 1.6–11,6 years) without plateau. Median progression free survival (PFS) after Bendamustine treatment was 16 months (95% CI: 11.7–20.4), data that compares favourably with patients' PFS to previous therapy (12 months, 95% CI: 6.5–17.5). Median PFS for patients who achieved CR/uCR is 32.6 months (95% CI: 19.9–45.4) versus 11 months in patients with PR (95% CI: 3.9–18.8). With a median follow-up for surviving patients of 12 months since Bendamustine treatment, the estimated OS at 3 years is 47% (+ SD 14%). Toxicity: No treatment related mortality has been described so far. Over 152 cycles, only 10 hospitalizations due to febrile neutropenia were reported. No one case of lysis tumoral syndrome has been reported. CONCLUSION. Bendamustine plus Rituximab is a good rescue treatment in non selected pretreated patients with mantle cell lymphoma. CR rate and duration of response seem to reproduce in current clinical practice the good data reported in previous clinical trials and compares favourably with other available treatments. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Eltrombopag is a thrombopoietin receptor agonist approved for primary chronic ITP patients. Due to the non-existence of clinical trials using eltrombopag in persistent and newly diagnosed ITP, there are no clear data about its usefulness in this setting. Aims: To evaluate efficacy and safety of eltrombopag in persistent, newly diagnosed and chronic ITP in routine clinical practice in Spain. Methods: Two hundred and twenty adult ITP patients from thirty Spanish centers who had been treated with eltrombopag and included in the Spanish Eltrombopag Registry were retrospectively evaluated. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: Here we report efficacy and safety results of primary ITP Spanish Eltrombopag Registry cohort. According to the standard definition, patients were allocated to newly diagnosed (n=30), persistent (n=30) and chronic (n=160) ITP groups. Each group is described separately in Table I. There are no statistical significant differences regarding response and duration of response among ITP groups. There is a trend towards a greater efficacy in newly diagnosed ITP with 93.3% of responses (platelet count ≥30 x109/L and at least two-fold increase the baseline count and absence of bleeding) and 86.7% of complete responses (CR; platelet count 〉100 x 109/L). Persistent ITP achieved 83.3% of responses and 80.0% of CR. Similarly 79.4% of responses with 73.1 of CR were observed in chronic ITP. Response rates were similar in all groups regardless all other studied parameters. Another trend towards a longer response duration in persistent ITP was found, with a median of 424 (IQR, 288-664) days. Response durations were similar in chronic ITP (median, 370 days; IQR, 174-624) and in newly diagnosed ITP (median, 378 days; IQR, 154-485). In newly diagnosed ITP, eight adverse events (AEs) with only three grade 3-4 AEs were observed. We reported three deaths; Two of them were due to upper respiratory tract infections in previously diagnosed pulmonary patients. A cerebral hemorrhage was the only death directly related to thrombocytopenia. In persistent ITP, four grade 1-2 AEs and two grade 3-4 AEs (one stroke, one cerebral bleeding) were reported. The only observed death was secondary to the mentioned cerebral hemorrhage. Twenty-one grade 1-2 AEs, ten grade 3-4 AEs and eight deaths (only two caused by bleeding) occurred in chronic ITP. Conclusion: Use of eltrombopag for treating persistent and newly diagnosed ITP is effective and safe. However, more studies are needed to confirm usefulness of TPO-RAs in this setting. Table 1. Patient characteristics Variable Newly-Diagnosed ITP (n = 30) Persistent ITP(n=30) Chronic ITP (n=160) Age, years, median [Q1;Q3] 66[46;79] 66[47;76] 61[47;75] Men/Women n 12/18 15/15 47/113 Charlson comorbidity Index 〉 1, n (%) 7(25.9) 5(17.2) 25(16.7) Months with ITP, median [Q1;Q3] 1[1;2] 6[4;10] 79[30;193] Past ITP treatments, median [Q1;Q3] Rituximab, n (%) Splenectomy, n (%) Romiplostim, n (%) 2[1;3] 3(10.7) 2(7.1) 3(10.7) 2[1;3] 5(17.2) 4(13.8) 4(13.8) 3[2;4] 43(28.3) 47(30.7) 37(24.3) Platelet count at start of eltrombopag treatment, (x109/L), median [Q1;Q3]Bleeding at start of eltrombopag treatment , n (%)Concomitant treatment, n (%) Corticoids Immunoglobulins Corticoids and Immunoglobulins 15[7;29] 13(43.3) 10(33.3) 6(60) 0 2(20) 14[6;26] 10(33.3) 9(30) 7(77.8) 0 2(22.2) 22 [9;38] 50 (31.3) 46 (28.8) 27 (57.4) 10 (21.3) 8 (17) Disclosures Off Label Use: We describe the possibility of using eltrombopag, an oral thrombopoietin receptor analog, for persistent and newly diagnosed ITP patients..

Description: Background: Eltrombopag is effective and safe for treating chronic immune thrombocytopenia (ITP) patients who have not responded to previous therapy. Interestingly, some patients in whom hemostatic platelet counts are achieved with eltrombopag may sustain the platelet response when eltrombopag ceases to be administered. However, the frequency of sustained responses after discontinuing eltrombopag without additional therapy for ITP is largely unknown. Methods: A total of 260 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry were retrospectively evaluated. The study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age was 62 [range, 18–93] years. There were 165 women and 95 men. According to the standard definition, patients were allocated to newly diagnosed (n=29), persistent (n=36) and chronic (n=195) ITP groups. The median time from diagnosis to eltrombopag initiation was 24 [range, 1–480] months. The median number of previous therapies was 3 [range, 0–10], including splenectomy (22%), rituximab (23%) and romiplostim (19%). The initial response rate to eltrombopag was 231/260 (89%), including 77% (n=201) cases of complete remission (platelet count ≥100 x 109/L). The median duration of eltrombopag treatment was 6 [range, 1–54] months. Eltrombopag was discontinued in 80 out of 201 (39.8%) patients who achieved CR. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=33), platelet count 〉400x109/L (n=29), patient’s request (n=5), aspartate aminotransferase elevation (n=3), diarrhea (n=3), thrombosis (n=3) and other reasons (n=4). For analysis of discontinuation, patients with follow-up 〈 6 months (n=15), newly diagnosed ITP (n=11) or patients who received concomitant or previous (6 months before) treatments at the start of eltrombopag use (n=5) were excluded. Of the 49 evaluable patients, 22 (45%) had an immediate relapse after stopping eltrombopag. One patient with sustained response after stopping treatment relapsed at 10 months. A total of 26 patients (53%) showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 [range, 6–25] months. These patients were characterized by a median time since ITP diagnosis of 46.5±114.1 months, with 4/26 having ITP

Description: Background and aims: Significant efforts have been made in international guidelines since 2009 to establish recommendations for the initial work-up of patients with suspected immune thrombocytopenia (ITP), and to define who should be treated and how. A previous retrospective study of 101 ITP patients identified important areas of inappropriateness in the diagnostic and therapeutic management of ITP (Lozano et al, 2016), which could negatively impact patient outcomes. This study was aimed to further analyze the level of implementation of current recommendations in the standard practice of adult ITP patients in an independent validation cohort, and compare it to the pre-guideline period. Methods: We collected retrospectively the clinical data of 146 primary adult ITP patients who initiated treatment with thrombopoietin receptor agonists (TPO-RA) between January 2012 and December 2014. Data on patient characteristics were obtained from medical records from November 2016 to January 2018 in a multicenter study from 19 secondary and tertiary Spanish hospitals. To evaluate the laboratory diagnosis and the appropriateness of treatment according to guidelines, two cohorts of patients were considered: "pre-group" and "post-group" depending on the date of diagnosis (before or after January 2010). Results: Patients in pre-group (n=71) and post-group (n=75) had a median follow-up from diagnosis of 13.6 years (7.5-54.2 years), and 4.6 years (2.2-7.6 years), respectively. The level of compliance of general diagnostic tests was analyzed and compared. Peripheral blood smear, an examination recommended by all recent guidelines, was performed in 84% of patients in the post-group, and in only 64% of those in the pre-group (P=0.007). Bone marrow assessment at diagnosis of the disorder was ordinarily performed in around half of the patients regardless of the period (54% and 47% in the pre- and post- groups, respectively; P=0.408). Remarkably, in 49% of the patients in the pre-group, bone marrow evaluation was primarily performed due to the department policy, whereas that reason decreased to 25% in the post-group (P=0.027). Moreover, in 21% and 9% of patients in the pre-group and post-group that underwent a bone marrow assessment at diagnosis, the peripheral blood film had not been previously examined (P=0.192). In our cohort, differences in the treatment patterns were analyzed. Prednisone was used as first line-therapy in 89% and 84% of pre- and post- groups, respectively (P=0.406). There was a significant decrease in the duration of first-line therapy with prednisone from start until withdrawal in the post-group compared with the pre-group (median 77 vs. 122 days, respectively; P=0.004). Following first-line treatment, more patients in the pre-group were exposed to further prednisone (45% vs. 25%, P=0.003), and also the number of second or subsequent lines of therapies with this corticosteroid were significantly higher (61 courses of prednisone retreatment in 32 patients vs. 22 courses in 19 patients in the pre- and post- groups, respectively; P=0.008). As expected, a higher proportion of patients in the pre-group underwent splenectomy, and also received more immunosuppressant and immunomodulatory drugs than those in the post-group prior to TPO-RA therapy (P

Description: Introduction: The management of immune thrombocytopenia (ITP) in pregnancy can be challenging as some patients either do not respond to or tolerate corticosteroids and intravenous immunoglobulin and only very few alternative ITP therapies are available during pregnancy. The use of thrombopoietin receptor agonists (Tpo-RA) which are likely to cross the placenta is not recommended during pregnancy but both romiplostim and eltrombopag have been exceptionally used to treat women with severe and refractory ITP during pregnancy. To better assess safety and efficacy of Tpo-RA during pregnancy, we performed an international multicentre observational retrospective study. Methods: To be included, the patients had to fulfill the following criteria: pregnant woman aged of 18 years and above, diagnosis of primary or secondary ITP according to international consensus guidelines, use of either eltrombopag of romiplostim for at least 1 week for treating ITP during pregnancy (before delivery), at least a month of follow-up after Tpo-RA initiation. Women who became pregnant while on Tpo-RA could be included even if the treatment was stopped if enough data on pregnancy outcome were available. Women treated with a Tpo-RA during pregnancy not for ITP were excluded. All clinical and biological data were collected by means of a standardized study form, whenever available, data on the neonates were also collected and analyzed. Data are presented as mean±SD or median (interquartile range [IQR]) for continuous variables, depending on their distribution. Categorical variables are presented as number (%). Results: In total, 12 women (mean age at time of pregnancy was 30.3 ± 5 years) fulfilling the eligibility criteria were included, for a total of 13 pregnancies and 14 neonates (one twin pregnancy) with an exposure to Tpo-RA. Nine of 12 patients had pre-existing chronic primary ITP (mean ITP duration = 11.8 ± 10.1 years) whereas ITP was newly-diagnosed during pregnancy in 3 cases. The median number of treatment-lines before the use of Tpo-RA was 3 [range 2-7] including splenectomy for 5 patients. Patients were treated transiently during pregnancy with either eltrombopag (n = 6; mean daily dose 50mg) or romiplostim (n = 6; mean maximal weekly dose 7.4 microg/kg). Two patients with chronic ITP were already on Tpo-RA when pregnancy was confirmed, and for 8 pregnancies, treatment with Tpo-RA was initiated only within 4 weeks before term in preparation for delivery. The median time of exposure to Tpo-RA during pregnancy was 4.4 weeks [range: 1-12 weeks]. No side-effects and especially no thromboembolic events were observed; none of the patients was on thromboprophylaxis. The mean platelet count at term was 91 x 109/L (median = 94 x 109/L [6-250]). Delivery occurred pre-term in 4 out of 13 pregnancies, mode of delivery was vaginal in 8 out of 13 pregnancies (with an epidural in 4 cases) and a C-section in 5. The platelet count was available at birth in 10 out of 13 neonates and neonatal thrombocytopenia was found in 5 (including 3 from the same mother). No case of neonatal thrombocytosis was observed. No neonatal complications attributable to the exposure to a TpoRA in the mother was observed. One neonate (whom the mother received 1 week of romiplostim in preparation for delivery) was diagnosed with trisomy 8 and died on day 7 and another neonate had a pulmonary artery stenosis diagnosed during fetal life (before the initiation or Tpo-RA in the mother), that was successfully operated at 2 weeks of life. A complete platelet response (CR) was achieved on Tpo-RA during pregnancy in 8/12 patients (66%) (5 of them received concomitant ITP therapy), a response (R) in 2 whereas no response was achieved in 2 patients with refractory ITP (table). Conclusion: Based on this preliminary results on a relatively small number of patients (more cases are expected) and taking into account that Tpo-RA was used only in preparation for delivery in 7/13 pregnancies, a temporary off-label use of a Tpo-RA over a short period of time for ITP during pregnancy seems safe for the mother and the neonate. The pattern and magnitude of response seems comparable to what is observed outside pregnancy but only few patients were treated with Tpo-RA alone. For now, the transient use of Tpo-RA during pregnancy should only be considered exceptionally for women with severe and refractory ITP. Disclosures Michel: Rigel: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Ghanima:Amgen: Consultancy, Honoraria; Bayer: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer/BMS: Research Funding. Anderson Tvedt:Alexion: Other: Advisory Board; Ablynx: Other: Advisory Board; Novartis: Other: Advisory Board. Bussel:Tranquil: Honoraria, Membership on an entity's Board of Directors or advisory committees; Physician Education Resource: Speakers Bureau; Kezar Life Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; UCB: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; 3S Bio: Speakers Bureau; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Momenta Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; RallyBio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Godeau:Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. OffLabel Disclosure: It reports some data about the use of either romiplostim or eltrombopag (thrombopoietin receptor agonists) to treat ITP during pregnancy. Both drugs are licensed for adult' ITP but are not supposed to be used in pregnant women

Description: Introduction Eltrombopag is an oral, non-peptide thrombopoietic receptor-agonist (TPO-RA). In chronic immune thrombocytopenic purpura (ITP) randomized–controlled trials proved to be effective, safe and well tolerated with reported response rates of 59%-88%. When eltrombopag is discontinued, platelet counts usually return to baseline within 2 weeks. However, certain patients may be able to discontinue TPO-RA and still maintain platelet counts above baseline without additional treatment. We report here 12 patients who presented sustained responses after discontinuing eltrombopag without substituting additional anti-ITP therapy. Patients and Methods Primary ITP was defined as a platelet count 〈 100 x 109/L in the absence of other causes or disorders that may be associated with thrombocytopenia. Patients received daily oral eltrombopag, at a starting dose of 50 mg/day adjusting the dose as needed up to a maximum of 75 mg/day based on the patient’s platelet count. Successful discontinuation of eltrombopag treatment was defined as a platelet count of 30,000/μl and 20,000/μl above initial baseline for at least 6 months off eltrombopag without substituting additional anti-ITP therapy. Results Our patients were 4 males and 8 females, with a mean disease onset age of 55 years (range, 28–79 years). The median time from diagnosis to eltrombopag start was 24 months (range, 1-480). 5 cases had ITP since less than 1 year. The median prior number of therapies was 5 (range, 1-7). All patients were refractory to corticosteroids. Six patients had received rituximab: Patient (P) 1, P2, P3, P6, P7 and P8. Seven patients were splenectomized. Three patients (P2, P6 and P8) who failed to respond to romiplostim were switched to eltrombopag. One romiplostim responder (P12) switched to eltrombopag because patient request. The median platelet count before starting treatment was 7 x 109/L (range, 1-97 x 109/l). At start, concomitant treatment was administered in 4 patients: P2, P3 and P9 corticosteroids. P5, intravenous immunoglobulin. The median maximum platelet count during treatment was 482 x109/l (range, 251-858 x109/l). One patient had a transient increase in leukocyte count reaching 12x109/L. The median duration of treatment was 5 months (range, 1-13) (Fig 1A): only one month in three patients. Nine patients stopped treatment due to platelets higher than 250 x 109/l. Initial stop of eltrombopag in P2 was failed because of low platelet counts and eltrombopag was reinitiated. After 8 months of re-treatment, eltrombopag could be stopped with no other treatments needed for over 6 months. In P1, P10 and P11 eltrombopag was stopped at 140, 178 and 138 x109/L platelets, respectively. After a median follow-up of 7 months (range, 6 – 20 months), ten patients maintain a platelet count greater than 100 x 109/L (Fig 1B) without any anti-ITP treatment. Discussion The possibility of eltrombopag cessation in a specific subset of patients has emerged. Recently, a prospective ongoing study has demonstrated that approximately 1/3 of patients (5 of 15) appear able to successful elective discontinuation of eltrombopag after 2 or more years of treatment. Nevertheless we have showed that the remission of ITP is feasible after short term treatment with eltrombopag (3 patients treated for only 1 month). Repeated short-term use of eltrombopag in chronic ITP has been reported. Patient P2 could succesfully reintroduce eltrombopag after initial treatment stop. In our data no factors predict which patients may discontinue eltrombopag. Disclosures: San Miguel: Jansen, Celgene Corporation, Onyx, Novartis, Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Description: Background: MCL is a heterogeneous disease and the existence of indolent clinical forms is increasingly recognized although their biological ground is not fully elucidated. The aim of this study was to propose a frontline tailored treatment for indolent clinical forms with a chemo-free regimen, ibrutinib in combination with rituximab. In addition, an extensive genomic study was associated to gain biological insight into these clinical forms. Methods: This is a multicenter single-arm, open-label, phase II study with a two-stage design conducted in 14 Spanish GELTAMO sites (NCT02682641). Centralized histology, PET-CT review as well as minimal residual disease (MRD) studies (qPCR and NGS in peripheral blood [PB] and bone marrow [BM]) and biological studies are conducted. A total of 50 previously untreated MCL patients with indolent clinical forms are planned to be recruited, defined by the following criteria: no symptoms attributable to MCL, ECOG 0-1, stable disease without therapy need at least for 3 months, non-blastoid variants, Ki-67