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Background: Chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS) are two of the most frequent hematological malignancies. CLL and MDS are also considerably heterogeneous in terms of clinical course and response to treatment, ranging from relatively indolent to extremely aggressive. Thus, open issues abound regarding the impact of CLL and MDS and their treatment on patients' quality of life (QoL). Patient-reported outcomes (PROs) have been identified as an emerging paradigm, aiming to capture the patient's perspective onselfassessed health status. Obviously, these data are critical with regards to the evaluation of the treatment effects and the patients' QoL, while also enabling the positioning of the patient as a key stakeholder within the healthcare decision making process. Novel methodologies and eHealth approaches can be valuable for the adoption of the PRO paradigm in real-world settings as they can promote richer, less obtrusive and preemptive communication which could facilitate early recognition of potential symptoms of disease or treatment adverse effects (e.g., adverse drug reactions, lack of physical activity, worsening of QoL etc.). Aims: In this , we present the lessons learned thus far from the implementation of the MyPal project, a Horizon 2020 Research & Innovation Action aiming to foster palliative care for patients with CLL and MDS by leveraging the ePRO paradigm. Methods: MyPal aspires to empower patients and their caregivers to more accurately capture their symptoms/conditions, communicate them in a seamless and effective way to their healthcare providers (HCPs);and, ultimately, to foster action through advanced methods of identification of important deviations relevant to the patient's state and QoL. To this end, MyPal developed a technical platform including a mobile app for patients with CLL and MDS, collecting information via standardized questionnaires and other information sources (e.g., wearable sensors), also enabling spontaneous symptoms reporting, educational material provision, motivational messages, discussion guides, notifications etc. A data intensive web-based dashboard platform is also provided for healthcare professionals, providing real-time analytics, enabling a better view of collected PROs and other relevant information on patients' health status. Currently, a randomised clinical study is being conducted in 4 European countries to evaluate the proposed intervention and its potential impact on patients' QoL. Results: Based on this experience, a number of key issues have emerged: (a) while patients are generally positive about the use of eHealth, they are still reluctant about engaging in eHealth clinical studies;(b) digital literacy levels differ across different age groups as well as among different cultural contexts;(c) the COVID-19 pandemic seriously hindered patient recruitment due to the widely adopted recommendations for patients to avoid visits to hospitals unless absolutely necessary but (d) the COVID-19 pandemic also highlighted the potential benefits for HCPs of using eHealth tools in order to deliver patient care in a more decentralized and patient-centric fashion. Summary/Conclusion: In conclusion, MyPal is likely to provide important new evidence about how digital health systems can be used to improve QoL and facilitate better communication between patients with hematological malignancies and HCPs.
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On behalf of the GRAALL group, the Czech Republic ALL group, the Finland ALL group and the EWALL group. Introduction. Treatment of older patients (pts) with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains an unmet medical need. Inotuzumab ozogamicin (INO), an anti-CD22 antibody conjugated to calicheamicin, is approved for the treatment of relapsed/refractory BCP-ALL in adults, sinusoidal obstruction syndrome (SOS) being the major adverse event associated with INO. A previous first line study conducted by the MDACC in pts 60 years or older successfully used INO in combination with a lower intensity version of the hyper-CVAD (mini-hyper-CVD). Due to the occurrence of SOS, the total doses were fixed at 1.3 mg/m² for cycle 1 followed by 3 cycles at 1 mg/m² (Kantarjian H et al. Lancet Oncol, 2018). Here, we aimed to assess the activity and safety of fractionated INO at a reduced dosage in combination with low-intensity chemotherapy as frontline therapy for older pts with CD22+ Philadelphia chromosome-negative (Ph-neg) BCP-ALL. Methods. EWALL-INO is a single arm prospective phase 2 multicentric study conducted in European centers belonging to the EWALL group. Eligibility criteria were pts aged 55y or older, performance status ≤2, and newly diagnosed CD22+ (20% or more of positive blast cells) Ph-neg BCP-ALL without central nervous system involvement. After a prephase including 5 days (D) of dexamethasone (DEX) 10mg per D and a single intrathecal injection (IT), the induction regimen was begun and split in 2 parts. Induction part I (Induc1) consisted of one triple IT, vincristine (VCR) 2 mg (1 mg over 70y) D1 D8 D15 D22 and DEX 20 mg D1D2 D8D9 D15D16 D22D23 combined with 3 injections of INO (0.8 mg/m² D1, 0.5 mg/m² D8 and D15). Induction part II (Induc2) was offered to pts in CR or CRp (CR with platelets < 100 G/l) after Induc1 or as salvage therapy. Induc2 consisted of DEX 20mg D1D8, cyclophosphamide (CY) 300 mg/m² D1 to D3, one triple IT D2 and 2 injections of INO (0.5 mg/m² D1 and D8). Pts in CR/CRp were programmed to receive 6 blocks of consolidation (Ara-C 1.5g/m²/12h adapted to renal clearance D1D2 and DEX 10mg/12h D1D2, cycles 1 and 4;Methotrexate (MTX) 1.5 g/m² over 24h D1, VCR 1 or 2 mg D1, one triple IT D2 and 6-mercaptopurin (6-MP) D1 to D7, cycles 2 and 5;CY 500 mg/m² D1D2, VP16 75 mg/m² D1D2, one triple IT D2 and MTX 25 mg/m² D1, cycles 3 and 6) followed by a POMP maintenance (VCR, 6-MP, MTX, DEX) during 18 months. Allograft was allowed after at least 3 blocks of consolidation at the discretion of the investigators. The evaluable population was pts who received at least 1 dose of INO. Analyses were by modified intention to treat and performed JUN 28, 2021. All pts gave informed consent. The study is registered at ClinicalTrials.gov under the NCT number: NCT03249870. Results. Between DEC 29, 2017 and JUN 22, 2021, 115 pts (out of 130 planned pts) were enrolled including 6 pts with screen failure. The first 90 eligible pts (up to MAR 1, 2021) were considered for this analysis to obtain a minimum of 4 months follow-up. Median age was 69y (range 55-84) and median follow-up for alive pts was 1.18 years (range 0.3-3.5). At time of analysis, 90 and 88 pts had started induc1 and induc2, respectively. Treatment related mortality was 2.2% (2/90) and CR/CRp rate was 85.5% (77/90, 6 CRp) after induc1. Three cases relapsed between induc1 and induc2 and 5 pts were salvaged by induc2 allowing to a CR/CRp rate of 87.7% (79/90, 8 CRp) after induc2. One pts died from refractory disease during induc2. One, 2, 3 4 and 5 injections of INO were administered to 2 (2.2%), 2(2.2%), 11 (12.2%), 2 (2.2%) and 73 pts (81.1%) respectively. Only 6 pts were allografted. One-year OS was estimated to be 78.5% (95%CI 68-85.9) and median OS was not reached. One-year relapse free survival was 74.5% (95CI 63.5-82.6) (Figure 1). Grade 3-4 liver toxicity was observed in 8 pts (8.8%) during the study including 3 pts (3.3%) developing SOS, 2 related to INO during induc1 and one occurred after transplant. Twenty-nine pts died during the follow-up, 16 from relapses (overall incidence 18%) and 13 from adverse events (overall incidence 14.4%), including one COVID19 fatal infection during consolidation. Conclusion. Fractionated inotuzumab ozogamicin at reduced doses (0.8/0.5/0.5/0.5 mg/m²) combined with low-intensity chemotherapy is a very active and well tolerated frontline therapy for older patients with CD22+ Ph-neg BCP-ALL. [Formula presented] Disclosures: Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Huguet: Novartis: Other: Advisor;Jazz Pharmaceuticals: Other: Advisor;Celgene: Other: Advisor;BMS: Other: Advisor;Amgen: Other: Advisor;Pfizer: Other: Advisor. Raffoux: ABBVIE: Consultancy;PFIZER: Consultancy;CELGENE/BMS: Consultancy;ASTELLAS: Consultancy. Boissel: CELGENE: Honoraria;Servier: Consultancy, Honoraria;Incyte: Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Novartis: Consultancy, Honoraria, Research Funding;Bristol-Myers Squibb: Honoraria, Research Funding;PFIZER: Consultancy, Honoraria;JAZZ Pharma: Honoraria, Research Funding;SANOFI: Honoraria. Dombret: Amgen: Honoraria, Research Funding;Incyte: Honoraria, Research Funding;Jazz Pharmaceuticals: Honoraria, Research Funding;Novartis: Research Funding;Pfizer: Honoraria, Research Funding;Servier: Research Funding;Abbvie: Honoraria;BMS-Celgene: Honoraria;Daiichi Sankyo: Honoraria. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. OffLabel Disclosure: Inotuzumab ozogamicin as first line therapy in newly diagnosed CD22+ Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia
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Background: SARS-CoV-2 infection may be a threat for those undergoing active anti-cancer therapy. We aim to study adverse events, efficacy, and immune response in Covid-19 vaccinated patients focusing on possibly interfering therapy. Methods: CoVigi is a prospective open-label multicentric phase 4 clinical study (EudraCT 2021-000566-14) enrolling patients on anti-cancer treatment. Vaccines from Pfizer-BioNTech, AstraZeneca, Johnson&Johnson, or Moderna are considered. Data on vaccination side effects, the onset and course of Covid-19, and quantitative analysis of anti-S and anti-N SARS-CoV-2 antibodies (Roche) and SARS-CoV-2 specific cellular response evaluated by IFN-gamma-release assay (Qiagen) and CD69 expression are recorded as follows: at the baseline (prior to the vaccination), prior to the 2nd dose, 4–8 weeks, 3, 6 and 12 months after the first dose. Results: The trial was initiated on March 22th. As of May 4th, 152 solid cancer and 103 hematooncology patients were enrolled. From preliminary baseline data, 22% of solid cancer and 29% of hematooncology patients had detectable levels of anti-S antibodies with a median of 106 U/ml (range 1.4–3666) and 84 U/ml (range 0.75–2528), respectively (p = 0.888). Surprisingly, only 44% solid cancer and 53% of hematooncology patients with detectable antibodies prior to the vaccination referred on covid-19 in medical history. In the Ab-positive cohort, the IFN-gamma level upon both CD4 and CD8 stimulation was 0.04 pg/ml (IQR 0.02–0.13), the CD69 expression on NKT-like cells increased to 10.9% (IQR 6.6–17.3), whereas in the Ab-negative cohort was 0.00 pg/ml (IQR 0.00–0.01 and to 7.5% (IQR 4.0–10.1), respectively (p < 0.001 and p = 0.079). Conclusions: Substantial number of cancer patients experienced SARS-CoV-2 infection during active anti-cancer treatment prior to vaccination, often with asymptomatic course. In SARS-CoV-2-immunized patients, we observed SARS-CoV-2 positive cellular response. The preliminary results with dynamics of immune response with 3-month follow-up will be presented at the conference. Acknowledgment: CZECRIN LM2018128, Roche Diagnostics, MMCI00209805, MHCZ/DRO (FNBr, 65269705). Clinical trial identification: EudraCT 2021-000566-14. Legal entity responsible for the study: Masaryk University. Funding: CZECRIN. Disclosure: All authors have declared no conflicts of interest.