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Autor: Cavalli, Franco

9 záznamů v Medvik Filtry

Článek

Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results

Martelli, Maurizio
Autor Martelli, Maurizio ORCID Sapienza University, Division of Hematology, Department of Translational and Precision Medicine, Rome, Italy
Ceriani, Luca
Autor Ceriani, Luca ORCID Institute of Oncology Research (IOR), Bellinzona, Switzerland Ente Ospedaliero Cantonale, Imaging Institute of Southern Switzerland, Lugano, Switzerland Università della Svizzera Italiana, Faculty of Biomedical Sciences, Lugano, Switzerland
Ciccone, Giovannino
Autor Ciccone, Giovannino ORCID AOU Città della Salute e della Scienza di Torino and CPO Piemonte, Clinical Epidemiology Unit, Turin, Italy
Ricardi, Umberto
Autor Ricardi, Umberto ORCID University of Turin, Department of Oncology, Turin, Italy
Kriachok, Iryna
Autor Kriachok, Iryna National Cancer Institute, Onco-Hematology Department, Kyiv, Ukraine
Botto, Barbara
Autor Botto, Barbara AOU Città della Salute e della Scienza, Department of Hematology, Turin, Italy
Balzarotti, Monica
Autor Balzarotti, Monica ORCID IRCCS Humanitas Research Hospital, Department of Medical Oncology and Hematology, Rozzano Milan, Italy
Tucci, Alessandra
Autor Tucci, Alessandra ORCID ASST Spedali Civili, Department of Haematology, Brescia, Italy
Usai, Sara Veronica
Autor Usai, Sara Veronica AO Brotzu - Ospedale Oncologico Businco, Unit of Hematology and Bone Marrow Transplant, Cagliari, Italy
Zilioli, Vittorio Ruggero
Autor Zilioli, Vittorio Ruggero ORCID ASST Grande Ospedale Metropolitano Niguarda, Division of Hematology, Milan, Italy

Journal of clinical oncology. 2024 ; 42 (34) : 4071-4083. [pub] 20240819

J Clin Oncol
ISSN 1527-7755
Medvik
Zdroj

PURPOSE: The role of consolidation radiotherapy in patients with primary mediastinal B-cell lymphoma (PMBCL) is controversial. METHODS: The IELSG37 trial, a randomized noninferiority study, aimed to assess whether irradiation can be omitted in patients with PMBCL with complete metabolic response (CMR) after induction immunochemotherapy. The primary end point was progression-free survival (PFS) at 30 months after random assignment. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a noninferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomly assigned. RESULTS: The observed events were considerably lower than expected; therefore, primary end point analysis was conducted when ≥95% of patients were followed for ≥30 months. Of the 545 patients enrolled, 268 were in CMR after induction and were randomly assigned to observation (n = 132) or radiotherapy (n = 136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95% CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95% CI, -0.97 to 7.46). The 5-year overall survival (OS) was 99% in both arms. Nonrandomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomly assigned patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSION: This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.

MeSH
B-buněčný lymfom * radioterapie mortalita patologie MeSH
doba přežití bez progrese choroby MeSH
dospělí MeSH
lidé středního věku MeSH
lidé MeSH
mladý dospělý MeSH
nádory mediastina * radioterapie mortalita patologie MeSH
protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
senioři MeSH
Check Tag
dospělí MeSH
lidé středního věku MeSH
lidé MeSH
mladý dospělý MeSH
mužské pohlaví MeSH
senioři MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
hodnocení ekvivalence MeSH
multicentrická studie MeSH
randomizované kontrolované studie MeSH

Článek

International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia

Blood. 2020 ; 135 (21) : 1859-1869. [pub] 20200521

ISSN 1528-0020
Medvik
Zdroj

Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL [IPS-E]). Individual patient data from 11 international cohorts of patients with early-stage CLL (n = 4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated immunoglobulin heavy variable gene (IGHV), absolute lymphocyte count higher than 15 × 109/L, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (1 point each), and separated low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) patients showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The C-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta-analysis of the training and validation cohorts, the 5-year cumulative risk for treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early-stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.

MeSH
chronická lymfatická leukemie genetika patologie terapie MeSH
klinické zkoušky jako téma statistika a číselné údaje MeSH
kombinovaná terapie MeSH
lidé MeSH
míra přežití MeSH
mutace * MeSH
nádorové biomarkery genetika MeSH
následné studie MeSH
nomogramy * MeSH
prognóza MeSH
progrese nemoci MeSH
retrospektivní studie MeSH
senioři MeSH
Check Tag
lidé MeSH
mužské pohlaví MeSH
senioři MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
multicentrická studie MeSH
pozorovací studie MeSH
práce podpořená grantem MeSH

Článek

Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study

Leukemia & lymphoma. 2019 ; 60 (1) : 172-179. [pub] 20170605

Leuk Lymphoma
ISSN 1029-2403
Medvik
Zdroj

The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m2/cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m2/cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

Článek

Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

Lancet oncology. 2018 ; 19 (11) : 1449-1458. [pub] 20181019

Lancet Oncol.
ISSN 1474-5488
Medvik
Zdroj

BACKGROUND: In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. METHODS: LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed. FINDINGS: Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1-94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51-0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. INTERPRETATIONS: Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma. FUNDING: Janssen Research & Development.

Článek

Efficacy and safety of frontline rituximab, cyclophosphamide, doxorubicin and prednisone plus bortezomib (VR-CAP) or vincristine (R-CHOP) in a subset of newly diagnosed mantle cell lymphoma patients medically eligible for transplantation in the randomized, phase 3 LYM-3002 study

Leukemia & lymphoma. 2018 ; 59 (4) : 896-903. [pub] 20180117

Leuk Lymphoma
ISSN 1029-2403
Medvik
Zdroj

This post-hoc subanalysis of the LYM-3002 phase 3 study assessed the efficacy and safety of substituting vincristine in rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHOP; n = 42) for bortezomib (VR-CAP; n = 38) in a subgroup of 80 mantle cell lymphoma (MCL) patients aged <60 years who did not receive stem cell transplantation (SCT) despite medical eligibility. Complete response (CR)/unconfirmed CR (CRu) rates were 67 vs. 39% (odds ratio 3.69 [95% CI(confidence interval): 1.31, 10.41]; p = .012). After 40 months median follow-up, median progression-free survival by independent radiology committee with VR-CAP vs. R-CHOP was 32.6 vs. 12.0 months (hazard ratio (HR) 0.59 [95% CI: 0.31, 1.13]; p = .108); median overall survival was not reached vs. 47.3 months (HR 0.81 [95% CI: 0.33, 1.96]; p = .634). Adverse events included neutropenia (92/76%), thrombocytopenia (70/10%) and leukopenia (65/50%). VR-CAP represents a potential alternative to R-CHOP in combined and/or alternating regimens for younger, SCT-eligible MCL patients.

Článek

Association between quality of response and outcomes in patients with newly diagnosed mantle cell lymphoma receiving VR-CAPversusR-CHOP in the phase 3 LYM-3002 study

Haematologica. 2017 ; 102 (5) : 895-902. [pub] 20170209

ISSN 1592-8721
Medvik
Zdroj

In the phase 3 LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered or ineligible for transplant, the median progression-free survival was significantly improved with VR-CAP (24.7versus14.4 months with R-CHOP;P<0.001). Thispost-hocanalysis evaluated the association between the improved outcomes and quality of responses achieved with VR-CAPversusR-CHOP in LYM-3002. Patients were randomized to six to eight 21-day cycles of VR-CAP or R-CHOP. Outcomes included progression-free survival, duration of response (both assessed by an independent review committee), and time to next anti-lymphoma treatment, evaluated by response (complete response/unconfirmed complete response and partial response), MIPI risk status, and maximum reduction of lymph-node measurements expressed as the sum of the product of the diameters. Within each response category, the median progression-free survival was longer for patients given VR-CAP than for those given R-CHOP (complete response/unconfirmed complete response: 40.9versus19.8 months; partial response: 17.1versus11.7 months, respectively); similarly, the median time to next anti-lymphoma treatment was longer among the patients given VR-CAP than among those treated with R-CHOP (complete response/unconfirmed complete response: not evaluableversus26.6 months; partial response: 35.3versus24.3 months). Within the complete/unconfirmed complete and partial response categories, improvements in progression-free survival, duration of response and time to next anti-lymphoma treatment were more pronounced in patients with low-and intermediate-risk MIPI treated with VR-CAP than with R-CHOP. In each response category, more VR-CAP than R-CHOP patients had a sum of the product of the diameters nadir of 0 during serial radiological assessments. Results of thispost-hocanalysis suggest a greater duration and quality of response in patients treated with VR-CAP in comparison with those treated with R-CHOP, with the improvements being more evident in patients with low- and intermediate-risk MIPI.LYM-3002 ClinicalTrials.gov: NCT00722137.