ABSTRACT
Background: Initially, the marketing authorization (MA) of EPAG and ROMI was to adult patients (p.) with ITP ≥12 months (m.) and refractory to other treatments (t.), splenectomized or contraindicated to splenectomy. The MA was extended for EPAG in 2019 to p. aged ≥1 year with ITP ≥6 m., refractory to other t. (corticoids (CS), IgIV). In 2017, French national guidelines suggested the use of TPO-RA as an option of t. in 2nd line (L). Aims: The PEPITE study, still ongoing, aims to assess the modalities of use, effectiveness and safety of TPO-RAs in reallife. Methods: Prospective, observational, multicenter study including adult p. who initiated TPO-RA with persistent (pITP) or chronic (cITP) ITP. Inclusions occurred between 12/21/2018 and 07/17/2020. Here's the interim analysis, cut-off date: 03/22/2021. Characteristics at baseline were presented in 114 p. (analyzed pop). Efficacy analysis of TPO-RA was assessed in p. with a platelet count (PLAT) <100 G/L at TPO-RA initiation (efficacy pop 113 p.). Responses were defined as: response (R) = PLAT ≥30 G/L, complete response (CR) = PLAT ≥100 G/L and non-response (NR) = PLAT <30 G/L. Results: 123 p. included through 40 centers by 25 hematologists and 15 internists, and 77 p. were still on TPO-RA at 6 m. At baseline, mean age 62.7 ± 20.1 years, 55% men, 29% with at least 1 cardiovascular risk factor. At diagnosis: median PLAT = 26 G/L [0 to 134 G/L], 31% of p. with bleedings. 97% of p. received at least one L of t. before TPO-RA: CS 96%, IVIG 56%, rituximab 47%, dapsone 18%, hydroxychloroquine 11%, danazol 6% and 7% of p. were splenectomized. Median number L of t. = 2 and 8% of p. had more than 4 L. Median time between diagnosis and TPO-RA initiation was 2.6 years [0.3 to 49.3 years], 33% of p. with pITP (n=21 with ITP 3 -<6 months, n=16 with ITP 6 - <12 months) and 67% with cITP. At TPO-RA initiation: 9% of p. were on CS and 48% p. had PLAT <30 G/L (median PLAT = 30 G/L), 95 p. (83%) received EPAG and 19 p. (17%) ROMI. For the 77 p. still on TPO-RA at 6 m., R rate = 97% and CR = 60%. Within 6 m., 10 p. had permanently (perm.) discontinued TPO-RA, main causes were therapeutic effect deemed sufficient (TEDS) for 6 p. and NR for 2 p. For the 27 p. still treated with TPO-RA at 18 m., R rate = 93% and CR = 48%. Within 18 m., 12 p. had perm. stopped TPO-RA, including 7 p. for TEDS and 1 p. NR. P. initiated TPO-RA with ITP 3 -<6 months (N = 21), 9 (43%) p. were still on TPO-RA at 6 months, 5 (56%) in CR. Over the entire follow-up, 24p. (21%) perm. discontinued TPO-RA, main causes were TEDS for 9 p., adverse event (AE) for 5 p. and absence of R for 4 p. Of the 105 p. treated with EPAG at least once, 62 (59%) experienced at least one AE, and 26 SAE occurred in 17 p. The most common AEs were respectively 6% for headache and 3% for SARS-CoV-2 infections, diarrhea, asthenia, insomnia, arthralgia and alopecia. Of the 40 p. treated with ROMI at least once, 19 (48%) experienced at least one AE and 17 SAEs occurred in 10 p. The most common AEs: SARS-CoV-2 infections (5%) and arthralgias (5%). No deaths related to TPO-RA was reported. Summary/Conclusion: Preliminary data from the PEPITE study show that TPO-RA are prescribed in early ITP, including 33% with pITP (18% with ITP 3-<6 m.) and are used in 7% of cases after splenectomy. At 6 m. R on t. was 97% and CR on t. was 60%. Within 6 m., 6 p. had perm. stopped TPO-RA due to TEDS. The real-life effectiveness and safety data for EPAG and ROMI are consistent with data reported in extension studies, with the specificity of occurrence of SARS-CoV-2. The final analysis is scheduled after 24 m.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global pandemic. Phase III trials have demonstrated excellent efficacies of mRNA vaccines against SARS-CoV-2 in large population studies (Baden LR, NEJM, 2021;Polack FP, NEJM, 2020). Immunosuppressed individuals such as chronic lymphocytic leukemia (CLL) patients are at risk for a suboptimal response to 2 vaccine doses (Herishanu Y, Blood, 2021). The French National Authority for Health recommends the use of a third dose in immunosuppressed patients. However, seroconversion rate after the triple-dose vaccine is not yet known. The objective of our study was to evaluate SARS-CoV-2 antibody responses after the first, second and third doses of the BNT162b2 and mRNA-1273 vaccines. Data were collected from 17 French Innovative Leukemia Organization (FILO) investigating centers and the French CLL patients' association (SILLC). SARS-CoV-2 IgG anti-Spike levels were measured at 4-6 weeks after each vaccine dose. A total of 530 patients and 14 controls were included in the study. Vaccine response was evaluated post-dose 1 for 158 CLL patients, post-dose 2, for 506 patients and post-dose 3 for 66 patients. Peripheral blood lymphocyte subsets were studied post-dose 2 by flow cytometry in 80 CLL patients and 14 controls. The median age of the patients was 71 years (range 37-93), 218 (40%) were treatment-naïve (TN), 136 (26%) had a prior CLL treatment and 176 (34%) were on therapy. Post-dose 1, the global response rate was 27% (43/158). TN patients had a response rate of 34% (23/67), similar to those who had a prior CLL treatment (33%,12/36), and higher compared to on-therapy patients (15%, 8/55, P=0.02). Post-dose 2, the global response rate was 52% (265/506). TN patients had the highest response rate of 72% (151/210) compared to previously treated patients, mostly by immunochemotherapy (60%, 78/130, P=0.02) and on-therapy patients (22%, 36/166, P<0.001) (Figure 1A). Among the 166 on-therapy patients, mostly receiving targeted agents, those receiving venetoclax monotherapy achieved a significantly higher response rate (52%, 12/23) than those treated with BTK inhibitors (BTKi) ibrutinib or acalabrutinib (22%, 23/104, P<0.001). Patients treated with venetoclax+anti-CD20 monoclonal antibodies (n=19) or venetoclax+BTKi (n=6) were all seronegative after the second dose of vaccine (Figure 1B). In multivariate analysis, the variables found to be significantly associated with seroconversion were age >65 years (OR 0.55, 95% CI 0.33-0.92, P=0.02), ongoing CLL treatment (OR 0.13, 95% CI 0.07-0.23, P<0.001) and gamma-globulins ≤6g/L (OR 0.41, 95% CI 0.19-0.88, P=0.03). Flow cytometry results suggest a differential balance of the T CD4+ cell subpopulations in Binet stage A and in patients on targeted therapy compared to healthy controls. Post-dose 2 seronegative patients were proposed a third dose and to date, 66 have been tested for the antibody response 4-6 weeks post-dose 3. The post-dose 3 response rate was 42% (28/66). TN patients and previously treated patients had a significantly higher response rate (57%, 16/28) compared to on-therapy patients (32%, 12/38, P=0.03). We further analyzed patients tested post-dose 2 with the Abbott Architect SARS-CoV-2 IgG anti-Spike assay (n=24). Those who achieved seroconversion after the third dose (n=10) had significantly higher titers post-dose 2 (median 12, IQR 3.0-40.8) compared to those who remained seronegative (n=14) (median 2.2, IQR 0.5-5.1, p<0.01), although both median values are considered below the threshold by the manufacturer. An additional cohort of 40 CLL patients who presented a SARS-CoV-2 infection prior to vaccination participated to the study and was analyzed independently. All patients achieved seroconversion after infection and a single dose of vaccine, even though 30% (n=12) had an ongoing CLL treatment. In conclusion, double-dose mRNA vaccination generated a humoral response in 52% of our CLL cohort and a third dose induced seroconversion in 42% of the patients who remained seronegat ve after the second dose. The major independent predictor of negative antibody response was ongoing treatment with BTKi. The strongest boost to immune response against the virus seems to be SARS CoV-2 infection, as a substantial increase in anti-Spike antibodies was observed in all CLL patients with prior infection, after a single dose vaccination.
ABSTRACT
Chronic lymphocytic leukemia (CLL) patients experience both humoral and cellular immune deficiency, with a reduced number of normal B lymphocytes, and hypogammaglobulinemia. Previous large studies on vaccination efficacy are scarce but it is well-established that CLL patients have a poorer response than normal subjects to vaccination and are at increased risk of infection. Efficacy of anti-SARS-Cov-2 vaccination in CLL has been recently published by the Israeli group (Herishanu, 2021) showing that among hematological malignancies, patients who presented CLL disease are the least responsive to vaccination. We have collected the results of a large cohort of 502 French patients after vaccination by either BNT162b2 or mRNA-1273 mRNA vaccine. Patients received 2 doses at a 4-week interval. For those who received the 3rd dose, the interval was usually longer (between 6 and 8 weeks after 2nd dose). The median time to sample collection for serology was 4 weeks, and IgG anti-SARS-CoV-2 Spike antibody levels were measured by commercially available tests. We evaluated patients after the 1st and 2nd doses and collected matched samples whenever possible. Patients who had a previous COVID-19 infection were analyzed separately. We evaluated 176 patients after the 1st dose and the global seroconversion rate was only 31% (55/176). We evaluated 455 patients after the 2nd dose, and the global rate of seroconversion was 54% (246/455). Matched samples after both first and second doses were available for 118 patients. In this cohort, among the 87 patients who were seronegative after the first dose, 42 patients (48%) became positive after the second dose. Most patients who remained seronegative after two doses, received the third dose. The administration of the third dose program started recently, therefore, to date, we have the results for 31 patients only. Among these patients, 18 remained negative after this 3rd dose, while 13 (42%) seroconverted. Therefore, if we extrapolate these data, it is expected that approximately only 70-75% of CLL patients will be protected by vaccination (either by two or three doses) at the end of the vaccination program. On the other hand, 40 patients who received at least one dose of vaccine had presented a COVID-19 infection before vaccination. In this group of patients, the humoral response was evaluated in 29 patients. All of them except one, presented very high anti-Spike antibodies titer, even after one dose, and the only patient who remained seronegative after vaccination was on prolonged anti-CD20 therapy for autoimmune thrombocytopenia. We also collected cases of COVID-19 infection post-vaccination. Nineteen patients presented a COVID-19 infection after vaccination, 11/19 presented the infection after the first dose, and 8/19 after the second dose. Among those eight patients, five presented the first symptoms within the first 2 weeks after the second dose and had a more severe COVID-19 infection while the three patients with a later onset of symptoms (4-6 weeks after vaccination) had very mild symptoms. All patients tested had no antibody response before COVID infection but had highly positive anti-Spike titers after infection. Currently, the COVID- 19 pandemic has settled down and it is difficult to know if the absence of post-vaccination COVID-19 infection is related to the slowing of the pandemic or if CLL patients are protected by cell-mediated immunity, even in the absence of antibody response. In conclusion, double-dose mRNA vaccination generated a humoral response in 54% of our CLL cohort, and a third dose induced seroconversion in 40% of the patients who were seronegative after the second dose. However, the strongest boost to the immune response against the virus seems to be the COVID-19 infection, as a substantial increase in anti-Spike antibodies was observed in all CLL patients after infection, even if they were negative post-vaccination.
ABSTRACT
With the emergence of targeted therapies, defining the best strategy for the treatment of previously untreated CLL patients remains challenging. The aim of this phase 2 study was to compare the efficacy of an association with ibrutinib and venetoclax (IV) to the standard FCR regimen in fit patients with intermediate-risk CLL defined by either unmutated IGHV status, 11q deletion, or complex karyotype in the absence of TP53 abnormality. Patients were randomized 1:1 between two treatment arms, i.e. FCR 6 cycles or IV. After a lead-in phase of ibrutinib as a single agent from the month (M)1 to M3, the total duration of treatment with IV was based on the response achieved at M9;if bone marrow (BM) MRD was <0.01% using flow cytometry, the treatment was continued for 6 additional months until M15 and then stopped;if BM MRD at M9 was ≥0.01%, the treatment with IV was continued for 18 additional months until M27. The primary endpoint was the percentage of patients with BM MRD <0.01% at M27 in both arms. We present here the preliminary results on the first evaluation done at M9 including CT-scan, BM biopsy, and MRD assessment in PB and BM after the inclusion of all the 120 patients as initially planned. One hundred and twenty patients were enrolled from September 2019 to February 2021. The median age was 59 [34-72] and 61 [34-74] years in the FCR and IV arms, respectively. The characteristics of the patients were well-balanced between the 2 arms in terms of gender (male 72% FCR, 74% IV), PS ECOG 0-1 (59% FCR, 68% IV), and Binet stage (A, B, and C 15, 64, 21% for FCR;8.5, 59, and 32% for IV). No major difference in terms of cytogenetic features was noted, all patients but one had unmutated IGHV. At the time of data cut-off for this interim analysis, the median follow-up for all cohort was 12.7 [4.5.9-21.4] months. The frequency of patients presenting all grades adverse events (AE) so far was 90% (grade ≥3: 45%) in the FCR arm and 80% (grade ≥3: 45%) in the IV arm. The rate of infusion-related reactions (IRR) in the FCR arm was 35% on cycle 1-day 1 (14% grade 3-4);for the IV arm, 5% of patients experienced tumor lysis syndrome (TLS) (grade 3 for 1 patient). Ibrutinib doses were reduced for seven patients (four permanently stopped and three resumed at a lower dose because of toxicities (digestive, hepatic, or hematological). Venetoclax was permanently discontinued before M9 in four patients (digestive toxicities and grade 4 neutropenia). Fifty-two serious adverse events were reported of which 22 were in the IV arm (among them one sudden death, one ischemic stroke, one acute coronary syndrome, two atrial fibrillations, two TLS, two acute renal failures, one hepatitis, one neutropenia, two COVID pneumonitis, and one osteoporotic fracture) and 30 in the FCR arm (among them five febrile neutropenia, one hemolytic anemia, one thrombocytopenia, three IRR, three TLS, three COVID pneumonitis, one acute myeloid leukemia, one myelodysplasic syndrome). All patients with COVID pneumonitis had a favorable evolution with the need for intensive care and convalescent plasma for three of them. The first 85 patients included in the study have reached M9 and among them, nine prematurely discontinued the study, (one active hemolysis, one ischemic stroke, one TLS, one hepatitis, and one sudden death in the IV arm;three hematologic toxicities and one early progression in the FCR arm). In the evaluated patients (n=74), 69% of patients in the FCR arm and 43% of patients in the IV arm achieved bone BM MRD <0.01%. The complete (CR, CRi) and partial response rates were 56 and 44% in the FCR arm and 74 and 26% in the IV arm, respectively. In conclusion, preliminary results show a lower BM MRD rate in the IV arm compared to the FCR arm at M9, with toxicity that remains significant and relatively similar between the two arms. However, BM MRD rate may improve after longer exposure to the IV combination and the analysis of the primary endpoint at M27 will be decisive in determining the best therapeutic strategy.
ABSTRACT
With the emergence of targeted therapies, defining the best strategy for the treatment of previously untreated CLL patients remains challenging. The aim of this phase 2 study was to compare the efficacy of an association with ibrutinib and venetoclax (IV) to the standard FCR regimen in fit patients with intermediate risk CLL defined by either unmutated IGHV status, 11q deletion or complex karyotype in the absence of TP53 abnormality. Patients were randomized 1:1 between two treatment arms, ie FCR 6 cycles or IV. After a lead-in phase of ibrutinib as a single agent from month (M)1 to M3, the total duration of treatment with IV was based on the response achieved at M9;if bone marrow (BM) MRD was < 0.01% using flow cytometry, the treatment was continued for 6 additional months until M15 and then stopped;if BM MRD at M9 was ≥ 0.01%, the treatment with IV was continued for 18 additional months until M27. The primary endpoint was the percentage of patients with BM MRD < 0.01% at M27 in both arms. We present here the preliminary results on the first evaluation done at M9 including CT-scan, BM biopsy and MRD assessment in PB and BM after the inclusion of all the 120 patients as initially planned. One hundred and twenty patients were enrolled from September 2019 to February 2021. The median age was 59 [34-72] and 61 [34-74] years in the FCR and IV arms, respectively. The characteristics of the patients were well balanced between the 2 arms in terms of gender (male 72% FCR, 74% IV), PS ECOG 0-1 (59% FCR, 68% IV) and Binet stage (A, B and C 15%, 64%, 21% for FCR;8.5%, 59% and 32% for IV). No major difference in terms of cytogenetic features was noted, all patients but one had unmutated IGHV. At the time of data cut-off for this interim analysis, the median follow-up for the all cohort was 11 [2.9 - 19.8] months. The frequency of all grades adverse events (AE) observed so far was 53% (grade 3-4, 24%) in the FCR arm and 47% (grade 3-4, 17%) in the IV arm. The rate of infusion-related reactions (IRR) in the FCR arm was 35% on cycle 1-day 1 (14% grade 3-4);for the IV arm, 6% of patients experienced tumor lysis syndrome (TLS) (grade 4 for 4 patients). ibrutinib doses were reduced for 7 patients (4 permanently stopped and 3 resumed at a lower dose because of toxicities (digestive, hepatic or haematological)). Venetoclax was permanently discontinued before M9 in 4 patients (digestive toxicities and grade 4 neutropenia). Forty serious adverse events were reported of which 15 in the IV arm (1 sudden death, 1 ischemic stroke, 2 atrial fibrillations, 2 clinical TLS, 1 hepatitis, 1 neutropenia, 4 COVID pneumonitis and one osteoporotic fracture) and 25 in the FCR arm (2 neutropenias, 1 anemia, 1 thrombocytopenia, 1 autoimmune haemolytic anemia, 3 IRR, 4 TLS, 2 COVID pneumonitis, 4 fever episodes of undetermined origin, 1 community-acquired pneumonia, 1 gastrointestinal toxicity, 1 confusion, 2 chest pains, 1 acute myeloid leukemia, 1 myelodysplasic syndrome). The patients with COVID pneumonitis had a favorable evolution with the need for intensive care and convalescent plasma for 3 of them. The first 60 patients included in the study have reached M9 and among them, 6 prematurely discontinued the study, 3 in each arm (active hemolysis, ischemic stroke and sudden death in the IV arm;2 grade 4 hematologic toxicities and 1 early progression in the FCR arm). In the evaluated patients (n=54), 71% of patients in the FCR arm and 48% of patients in the IV arm achieved bone BM MRD < 0.01%. The complete (CR, CRi) and partial response rates were 54% and 46% in the FCR arm and 76% and 24% in the IV arm respectively. In conclusion, the preliminary results show a lower BM MRD rate in the IV arm compared to the FCR arm at M9, with a toxicity that remains significant and relatively similar between the two arms. However, BM MRD rate should improve after longer exposure to the IV combination and the analysis of the primary endpoint at M27 will be decisive in determining the best therapeutic strategy. Disclosures: Quinquenel: Abbvie: Honoraria;Jansse : Honoraria;AstraZeneca: Honoraria. Laribi: Le Mans Hospital: Research Funding;Novartis: Other: Personal Fees, Research Funding;Takeda: Other: Personal Fees, Research Funding;BeiGene: Other: Personal Fees;IQONE: Other: Personal Fees;AbbVie: Other: Personal Fees, Research Funding;Astellas Phama, Inc.: Other: Personal Fees;AstraZeneca: Other: Personal Fees;Jansen: Research Funding. Cymbalista: Lilly-LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;ASTRA ZENECA: Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Leblond: AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Lilly: Consultancy;AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support;Roche: Honoraria;Amgen: Honoraria;Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress;Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress;Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Ferrant: Janssen: Other: Travel, Accommodations, Expenses;AbbVie: Honoraria, Other: Travel, Accommodations, Expenses;AstraZeneca: Honoraria. de Guibert: Janssen: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria;Gilead: Consultancy, Honoraria. Feugier: Astrazeneca: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Amgen: Honoraria;Janssen: Consultancy, Honoraria. Cartron: Roche, Celgene-BMS: Consultancy;Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Ysebaert: Abbvie, AstraZeneca, Janssen, Roche: Other: Advisory Board, Research Funding.
ABSTRACT
Introduction Initialement, l’indication pour EPAG et ROMI concernait les patients adultes splénectomisés ou contre-indiqués à la splénectomie, présentant un PTI ≥12 mois, et réfractaires aux autres traitements. L’AMM a été étendue pour EPAG en 2019 aux patients ≥1 an, présentant un PTI ≥6 mois, et réfractaires aux autres traitements (corticoïdes, immunoglobulines). Le PNDS 2017 suggère que l’utilisation des ARTPO peut s’envisager dès la 2e ligne de traitement. L’étude PEPITE, toujours en cours, a pour objectif d’évaluer l’utilisation en vie réelle des ARTPO dans le PTI de l’adulte en France. Patients et méthodes Etude prospective, observationnelle, multicentrique incluant des patients ayant initié un ARTPO pour un PTI persistant (PTIp) ou chronique (PTIc). La période d’inclusion était du 21/12/2018 au 17/07/2020, avec des données collectées jusqu’à 24 mois de suivi. Cet présente les données de l’analyse intermédiaire, avec une date du cut-off au 22/03/2021. L’analyse de l’efficacité des ARTPO a été réalisée uniquement chez les patients avec un taux de plaquettes (PLAQ)<100G/L à l’initiation. La réponse était définie comme suivant: réponse (R)=PLAQ ≥ 30G/L, réponse complète (RC)=PLAQ ≥ 100G/L et non-réponse (NR)=PLAQ<30G/L. Résultats 123 patients ont été inclus dans 40 centres, 25 hématologues et 15 médecins internistes. La population analysée incluait 114 patients et la population d’efficacité de 113 patients. À l’inclusion, l’âge moyen était de 62,7 ans±20,1 ans, 55 % d’hommes et 29 % avec au moins un facteur de risque cardiovasculaire. Au diagnostic le taux de PLAQ médian était de 26 G/L [0 à 134 G/L] et 31 % des patients présentaient un syndrome hémorragique. 97 % des patients avaient reçu au moins 1 L de traitement avant ARTPO: corticoïdes 96 %, IgIV 56 %, rituximab 47 %, dapsone 18 %, hydroxychloroquine 11 %, danazol 6 % et 7 % des patients étaient splénectomisés. Le nombre médian de L de traitement était de 2 et 8 % des patients avaient eu plus de 4 L. Le délai médian entre le diagnostic et l’initiation de l’ARTPO était de 2,6 ans [0,3 à 49,3 ans]. Sur les 113 patients, 33 % des patients avaient un PTIp (n=21 avec un PTI 3–<6 mois, n=16 avec un PTI 6–<12 mois) et 67 % un PTIc. A l’instauration de l’ARTPO, 9 % des patients avaient un traitement concomitant par corticoïdes et 48 % des patients avaient un taux de PLAQ<30 G/L. 95 patients (83 %) ont reçu de l’EPAG et 19 patients (17 %) du ROMI. L’analyse d’efficacité était sur 113 patients avec PLAQ <100 G/L. Pour les 77 patients toujours sous traitement à 6 mois, le taux de R=97 % et RC=60 %. Avant 6 mois de suivi, 10 patients avaient définitivement arrêté l’ARTPO, dont 6 pour une réponse maintenue sans traitement et 2 pour NR. Pour les 27 patients toujours sous traitement à 18 mois, le taux de R=93 % et RC =48 %. Avant 18 mois de suivi, 12 patients avaient définitivement arrêté l’ARTPO, dont 7 pour une réponse maintenue sans traitement et 1 pour NR. Tous les patients ayant un ARTPO avec un PTI 3–<6 mois d’évolution (n=9) et toujours traités à 6 mois, le taux de R=100 % et RC=56 %. Sur l’ensemble du suivi, 24 patients (21 %) ont interrompu définitivement l’ARTPO. Les causes principales d’arrêt définitif étaient: réponse maintenue sans traitement (n=9), évènement indésirable (EI) (n=5) et NR (n=4). Les données de tolérance étaient analysées sur l’ensemble de la population (n=123). Sur les 105 patients traités par EPAG, 62 (59 %) ont présenté au moins un EI, et 17 patients ont présenté 26 EI sévères. Les EIs les plus fréquents: céphalées (6 %), infections par le SARS-CoV-2 (3 %), diarrhée (3 %), asthénie (3 %), insomnie (3 %), arthralgie (3 %) et alopécie (3 %). Sur les 40 patients traités par ROMI, 19 (48 %) ont présenté au moins un EI et 10 patients ont présenté 17 EI sévères. Les EIs les plus fréquents: infections par SARS-CoV-2 (5 %) et arthralgies (5 %). Aucun décès relié aux traitements par ARTPO n’a été déclaré. Conclusion Les données préliminaires de l’étude PEPITE indiquent que les ARTPO sont prescrits de plus en plus tôt dans le PTI de l’adulte dont 33 % dans le PTIp (18 % avant 6 mois) et sont utilisés dans 7 % des cas après splénectomie. À 6 mois, la R était de 97 % et la RC était de 60 %. Avant 6 mois, 6 patients avaient définitivement arrêté l’ARTPO pour réponse maintenue sans traitement. Les données d’efficacité et de tolérance en vie réelle d’EPAG et de ROMI sont conformes aux données préalablement rapportées des études d’extension avec comme particularité les infections à SARS-COV2. L’analyse finale est prévue après 24 mois de suivi.