33 research outputs found
Management of Oral Hydroxyurea-Related Ulcers: A Cases Series
No full textHydroxyurea (HU) is an anti-cancer agent commonly used in myeloproliferative Philadelphia negative disorders as polycythemia vera (PV), essential thrombocitosis (ET) and myelofibrosis (MF). [...
Potential Benefit of Involved-Field Radiotherapy for Patients With Relapsed-Refractory Hodgkin's Lymphoma With Incomplete Response Before Autologous Stem Cell Transplantation
No full textOvercoming barriers to referral for CAR T-cell therapy in patients with non-Hodgkin aggressive B-cell lymphomas: A Delphi consensus
No full text: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of aggressive B-cell non-Hodgkin lymphoma, particularly in relapsed/refractory large B-cell lymphoma and mantle cell lymphoma. Despite its transformative potential, significant challenges persist in optimizing patient identification and referral pathways to ensure timely and equitable access. This expert consensus, developed through the Delphi methodology, analyzes key barriers to the referral process and proposes structured solutions to enhance collaboration between referring treatment centers (RTCs) and qualified treatment centers (QTCs). Our findings highlight the importance of early and timely identification of CAR T-eligible patients through standardized disease assessments and strategies to streamline patient access through structured collaboration between RTCs and QTCs that can help overcome patient-specific logistical challenges. Proposed solutions should be broadly applicable across different health care systems. Addressing these clinical and logistical barriers in the referral process will be crucial for maximizing the benefits of CAR T-cell therapy and expanding its accessibility to a broader patient population
Cost-Utility Analysis Comparing Pegcetacoplan to Anti-C5 Monoclonal Antibodies in the Treatment of Paroxysmal Nocturnal Hemoglobinuria
No full textSergio Di Matteo,1 Roberto Freilone,2 Giacomo Matteo Bruno,1,3 Rosario Notaro,4 Sabrin Moumene,1 Nicoletta Martone,5 Cristina Teruzzi,5 Antonio Ciccarone,1 Giorgio Lorenzo Colombo1,3 1Center of Research, SAVE Studi - Health Economics and Outcomes Research, Milan, Italy; 2Dipartimento di Oncologia - Direttore SC Ematologia, Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino e componente Tumor Molecular Board (TMB) Regione Piemonte, Torino, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, Italy; 4Direttore S.C. Core Research Laboratory in ISPRO, Firenze, Italy; 5Sobi S.r.l., Milano, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email [email protected]: Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease characterized by hemolytic episodes and associated with significant clinical burden. The introduction of C5 inhibitory monoclonal antibodies (C5i) represented a major breakthrough in PNH treatment, effectively reducing intravascular hemolysis (IVH) but showing limited impact on extravascular hemolysis (EVH). In 2021, the C3 inhibitor pegcetacoplan was approved by EMA and recently reimbursed in Italy, which also has the advantages in the reduction of both IVH and EVH, increasing hemoglobin values and simultaneously improving the quality of life and fatigue of patients. A cost-utility analysis was developed to compare pegcetacoplan to C5i (eculizumab and ravulizumab) in the PNH population who remain anemic after treatment with C5i for at least 3 months.Materials and Methods: The analysis employed a Markov model with a 5-year time horizon whereby patients can transition among 3 PNH health states, adopting the perspective of the Italian NHS. Efficacy data were sourced from the PEGASUS study, with drug prices reflecting ex-factory costs. Additionally, costs associated with resource utilization, adverse events, and complications were estimated based on outpatient and hospital care rates, excluding indirect expenses. Utility and disutility values related to transfusions were also considered, with pegcetacoplan allowing for dose escalation.Results: The cumulative cost of treatment per individual patient at 5 years was estimated to be € 1,483,454 for pegcetacoplan, € 1,585,763 for eculizumab, and € 1,574,826 for ravulizumab. Pegcetacoplan demonstrated a superior increase in quality-adjusted life years (QALYs) compared to both eculizumab (0.51 increase) and ravulizumab (0.27 increase). Furthermore, pegcetacoplan showed a reduction in complication management costs (€ 22,891 less compared to eculizumab and € 22,611 less compared to ravulizumab) and lower transfusion-related expenses (€ 14,147 less than both C5i treatments).Conclusion: Pegcetacoplan emerged as the dominant strategy in this analysis, being more effective, less expensive and improves quality of life in the analyzed population affected by PNH.Keywords: PNH, pegcetacoplan, eculizumab, ravulizumab, IVH, EVH, cost-utility analysis, pharmacoeconomic
Philadelphia-Negative MPN: A Molecular Journey, from Hematopoietic Stem Cell to Clinical Features
No full textPhiladelphia negative Myeloproliferative Neoplasms (MPN) are a heterogeneous group of hematopoietic stem cell diseases. MPNs show different risk grades of thrombotic complications and acute myeloid leukemia evolution. In the last couple of decades, from JAK2 mutation detection in 2005 to the newer molecular trademarks studied through next generation sequencing, we are learning to approach MPNs from a deeper perspective. Here, we intend to elucidate the important factors affecting MPN clonal advantage and the reasons why some patients progress to more aggressive disease. Understanding these mechanisms is the key to developing new treatment approaches and targeted therapies for MPN patients
Efficacy and safety of bendamustine, rituximab and bortezomib treatment in relapsed/refractory Waldenstrom Macroglobulinaemia: results of phase 2 single‐arm FIL‐BRB trial
No full textThis multicentre phase II study Fondazione Italiana Linfomi (FIL)-bortezomib plus rituximab plus bendamustine (BRB) tested a combination of bendamustine (90 mg/m2 on days 1–2), rituximab (375 mg/m2 intravenously on day 1) and bortezomib (1.3 mg/m2 sc on days 1, 8, 15, 22) every 28 days for six cycles in 38 symptomatic patients with relapsed/refractory Waldenstrom macroglobulinaemia (RR-WM). Moreover, MYD88L265P and CXCR4S338X mutations were tested by droplet digital polymerase chain reaction (ddPCR) both at baseline and at the end of treatment in 21 patients. Overall response rate at the end of therapy was 84.6%, including 4 (11%) complete remission, 15 (39%) very good partial response, 12 (32%) partial responses according to IWWM response criteria. At 18, 24 and 30 months, progression-free survival was 84.2% (95% CI 68.2%–92.6%), 81.5% (95%CI 65.1–90.7) and 78.8% (95%CI 62.0–88.8) respectively. At 18 months, the Overall survival was 92.1% (95%CI 77.5%–97.4%). Overall, 19 patients (50%) experienced grade 3–4 haematological toxicity, mainly thrombocytopenia, and grade 1–3 neuropathy rate was about 10% and required bortezomib dose reduction but did not result in treatment interruption. Moreover, BRB treatment induced the high rates of undetectable molecular minimal residual disease (MRD) at the end of the therapy. BRB regimen used as second line is an effective and well-tolerated salvage treatment for relapsed refractory Waldenstrom macroglobulinaemia patients. MRD monitoring showed promising efficacy in clearing the residual disease
Interim positron emission tomography response-adapted therapy in advanced-stage hodgkin lymphoma: Final results of the phase II part of the HD0801 study
No full textPurpose The clinical impact of positron emission tomography (PET) evaluation performed early during firstline therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. Patients and Methods The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. Results In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2- negative patients. Conclusion Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup. © 2016 by American Society of Clinical Oncology
Real life clinical outcomes of relapsed/refractory diffuse large B cell lymphoma in the rituximab era: The STRIDER study
No full textBackground: Relapse and refractory (R/R) rates after first-line R-CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. Aims: We conducted a retrospective real-world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. Material and methods: Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. Results: At a median follow-up of 50 months, 5-year overall survival from diagnosis (OS-1) was 66.5%, and 2-year progression-free survival (PFS-1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R-CHOP. Most employed salvage treatments included platinum salt-based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS-2 and PFS-2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS-2 or PFS-2 in patients treated with platinum-based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of <2 sites were associated with better OS-2. Discussion: Our findings confirm very poor outcomes of R/R DLBCL in the rituximab era. Widespread approval by national Medicine Agencies of novel treatments such as CAR-T cells and bispecific antibodies as second-line is eagerly awaited to improve these outcomes
A Real Life Survey On Erythropoietin Alpha Treatment In a Cohort Of 1049 Low Risk MDS Patients: An Italian MDS Registry Study
No full textPrognostic role of interim PET in patients with follicular lymphoma: a post-hoc study of FOLL12 trial by FIL
No full textWe analysed interim metabolic response (iPET) in a subset of Follicular Lymphoma (FL) patients enrolled in the randomized FOLL12 trial. Grade 1-3a FL patients with an iPET performed between cycles 4 and 5 of first-line immunochemotherapy (ICT) were included; PET scan had to be centrally reviewed for the definition of Deauville Score (DS) and were considered positive for DS4-5. Overall 123 patients out of 211 with iPET were available for central review. Of these, 43% were older than 60, 33% had high-risk FLIPI2, and 47% received R-Bendamustine as the induction regimen. iPET showed a complete metabolic response (CMR) in 83% of cases. CMR at the end of induction therapy (eoiPET) was confirmed in 91% of iPET-negative patients. The 5-year PFS was 70% for iPET-negative (95% CI: 60-78%) and 34% for iPET-positive (95% CI: 15-55%) cases (p<0.01). In multivariate analysis, iPET+ was an independent prognostic factor for PFS (HR 2.82, 95% CI: 1.47-5.42). Combining iPET and eoiPET, the 3-year PFS was 78% for both negative iPET and eoiPET, with a reduced risk of progression compared to double-positive cases for double iPET/eoiPET cases. The 5-year OS was 96% for iPET-negative (95% CI: 89-98%) and 85% for DS 4-5 (95% CI: 61-95%), HR 5.74 (95% CI: 1.65-20, p=0.006). Our results confirm that iPET in patients with FL treated with standard ICT is a strong prognostic factor. Assessment of early metabolic response in FL may be considered for defining a novel generation of early response-adapted trials in FL. NCT02063685
