ORCID Profile
0000-0003-1709-9492
Current Organisations
University of St Andrews
,
Northumbria University
,
IRCCS Humanitas Research Hospital
,
Humanitas University
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Publications
Safety of autologous fat grafting in breast cancer: a multicenter Italian study among 17 senonetwork breast units autologous fat grafting safety: a multicenter Italian retrospective study.
Publisher: Springer Science and Business Media LLC
Date: 09-11-2021
DOI: 10.1007/S10549-021-06444-9
Abstract: Autologous fat grafting (AFG), defined as the re-implant to the breast of fat tissue from different body areas, has been firstly applied to esthetic plastic surgery and then has moved to reconstructive surgery, mainly used for scar correction and opposite breast altering. Nevertheless, due to the potentially unsafe stem-like properties of adipocytes at the tumoral bed level, no clear evidence of the procedure's oncological safety has been clearly documented at present. We retrospectively collected data of early breast cancer (BC) patients from 17 Italian Breast Units and assessed differences in terms of locoregional recurrence rate (LRR) and locoregional recurrence-free survival (LRFS) between patients who underwent AFG and patients who did not. Differences were analyzed in the entire cohort of invasive tumors and in different subgroups, according to prognostic biological subtypes. With a median follow-up time of 60 months, LRR was 5.3% (n = 71) in the matched population, 3.9% (n = 18) in the AFG group, and 6.1% (n = 53) in the non-AFG group, suggesting non-inferiority of AFG (p = 0.084). Building Kaplan-Meier curves confirmed non-inferiority of the AFG procedure for LRFS (aHR 0.73, 95% CI 0.41-1.30, p = 0.291). The same effect, in terms of LRFS, was also documented among different biological subtypes (luminal-like group, aHR 0.76, 95% CI 0.34-1.68, p = 0.493 HER2 enriched-like, aHR 0.89, 95% CI 0.19-4.22, p = 0.882 and TNBC, aHR 0.61, 95% CI 0.12-2.98, p = 0.543). Our study confirms in a very large, multicenter cohort of early BC patients that, aside the well-known benefits on the esthetic result, AFG do not interfere negatively with cancer prognosis.
An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers
Publisher: Springer Science and Business Media LLC
Date: 12-2016
The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of th
Publisher: Springer Science and Business Media LLC
Date: 03-09-2009
DOI: 10.1007/S10549-009-0512-0
Abstract: Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer (BC) regardless of the use of adjuvant systemic therapy. This is a retrospective analysis of 2,887 node-positive BC patients enrolled in the BIG 02-98 adjuvant study, a randomised phase III trial whose primary objective was to evaluate disease-free survival (DFS) by adding docetaxel to doxorubicin-based chemotherapy. In the current analysis, the effect of body mass index (BMI) on DFS and overall survival (OS) was assessed. BMI was obtained before the first cycle of chemotherapy. Obesity was defined as a BMI >or= 30 kg/m2. In total, 547 (19%) patients were obese at baseline, while 2,340 (81%) patients were non-obese. Estimated 5-year OS was 87.5% for non-obese and 82.9% for obese patients (HR 1.34 P = 0.013). Estimated 5-years DFS was 75.9% for nonobese and 70.0% for obese patients (HR 1.20 P = 0.041). Ina multivariate model, obesity remained an independent prognostic factor for OS and DFS. In this study,obesity was associated with poorer outcome in node-positive BC patients. Given the increasing prevalence of obesity worldwide, more research on improving the treatment of obese BC patients is needed.
Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study
Publisher: Elsevier BV
Date: 04-2021
Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial
Publisher: Elsevier BV
Date: 04-2016
Familial haploidentical challenging unrelated donor Allo-SCT in advanced non-Hodgkin lymphomas when matched related donor is not available
Publisher: Springer Science and Business Media LLC
Date: 02-03-2015
DOI: 10.1038/BMT.2015.22
Haploidentical stem cell transplantation (Haplo-HSCT) with nonmyeloablative conditioning regimen (NMAC) and postinfusion cyclophosphamide in advanced non-Hodgkin lymphoma (NHL) patients.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-05-2014
A New View of the Solar Interface Region from the Interface Region Imaging Spectrograph (IRIS)
Publisher: Springer Science and Business Media LLC
Date: 05-2021
DOI: 10.1007/S11207-021-01826-0
Abstract: The Interface Region Imaging Spectrograph (IRIS) has been obtaining near- and far-ultraviolet images and spectra of the solar atmosphere since July 2013. IRIS is the highest resolution observatory to provide seamless coverage of spectra and images from the photosphere into the low corona. The unique combination of near- and far-ultraviolet spectra and images at sub-arcsecond resolution and high cadence allows the tracing of mass and energy through the critical interface between the surface and the corona or solar wind. IRIS has enabled research into the fundamental physical processes thought to play a role in the low solar atmosphere such as ion–neutral interactions, magnetic reconnection, the generation, propagation, and dissipation of waves, the acceleration of non-thermal particles, and various small-scale instabilities. IRIS has provided insights into a wide range of phenomena including the discovery of non-thermal particles in coronal nano-flares, the formation and impact of spicules and other jets, resonant absorption and dissipation of Alfvénic waves, energy release and jet-like dynamics associated with braiding of magnetic-field lines, the role of turbulence and the tearing-mode instability in reconnection, the contribution of waves, turbulence, and non-thermal particles in the energy deposition during flares and smaller-scale events such as UV bursts, and the role of flux ropes and various other mechanisms in triggering and driving CMEs. IRIS observations have also been used to elucidate the physical mechanisms driving the solar irradiance that impacts Earth’s upper atmosphere, and the connections between solar and stellar physics. Advances in numerical modeling, inversion codes, and machine-learning techniques have played a key role. With the advent of exciting new instrumentation both on the ground, e.g. the Daniel K. Inouye Solar Telescope (DKIST) and the Atacama Large Millimeter/submillimeter Array (ALMA), and space-based, e.g. the Parker Solar Probe and the Solar Orbiter , we aim to review new insights based on IRIS observations or related modeling, and highlight some of the outstanding challenges.
Transverse Wave Induced Kelvin–Helmholtz Rolls in Spicules
Publisher: American Astronomical Society
Date: 23-03-2018
Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-04-2023
DOI: 10.1200/JCO.22.01134
Abstract: This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m 2 ) + gemcitabine (1,000 mg/m 2 ) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018 median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine hazard ratio [HR], 0.88 95% CI, 0.729 to 1.063 P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82 95% CI, 0.694 to 0.965 P = .02). The median OS (427 events 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82 95% CI, 0.680 to 0.996 P = .045). At a 16-month follow-up (cutoff, April 3, 2020 median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine HR, 0.82 95% CI, 0.687 to 0.973 P = .0232). At the 5-year follow-up (cutoff, April 9, 2021 median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80 95% CI, 0.678 to 0.947 P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
Lower Relapse and Better PFS Among Chemosensitive Patients Undergoing Allogeneic Transplantation By Haploidentical Compared With HLA-Identical DONOR: Results On A Cohort Of 94 Patients With Hodgkin’S
Publisher: American Society of Hematology
Date: 15-11-2013
DOI: 10.1182/BLOOD.V122.21.2144.2144
Abstract: haploidentical stem cell transplantation (SCT) represents an alternative option for those patients lacking a HLA-identical donor. Patients with relapsed or refractory Hodgkin's lymphoma may benefit from allogeneic SCT and, in particular, patients without a HLA-identical donor may receive SCT from a haploidentical one. The aim of this retrospective analysis is to compare outcome of HL patients undergoing allogeneic SCT from haploidentical vs. HLA-id. Donor. patients with diagnosis of HL who received allogeneic SCT at Istituto Clinico Humanitas (Milan, Italy) and Institut Paoli-Calmettes (Marseille, France) were included in the analysis. Outcome was estimated according to SC source (HLA-id. vs. haplo) and disease status at transplant: CR, PR or SP/PD. a total of 58 and 36 patients received SCT from a HLA-id. and haploidentical donor, respectively. SCT were performed from February 1999 to December 2012. Ninety-two patients received reduced-intensity conditioning all but one patient in haplo group received post-transplant cyclophosphamide as GVHD prophylaxis. Median follow-up was 63 months (range: 6-160) in HLA-id. group and 20 months (range: 6-50) in haplo group. In HLA-id. group, 2-year PFS was 62%, 33% and 17% among patients in CR, PR or SD/PD before allogeneic SCT, respectively 2-year PFS in haplo patients was 86%, 53% and 0% among CR, PR and SD/PD patients. Results are shown in Table 1. Notably, a lower number of relapse events were observed in chemosensitive patients in haplo group compared with HLA-id.: 1/21 vs. 7/28 among CR patients and 2/9 vs. 10/18 among those in PR (see Table 1) this translates into better PFS after haplo-SCT. Conversely, outcome of refractory patients confirmed to be poor in both groups. At last follow-up, among the 30 chemosensitive patients receiving haplo-SCT, last relapse occurred at day +392 post-SCT. present analysis showed better PFS in haplo group among high-risk, chemosensitive (CR + PR) patients compared with HLA-id. and better OS among patients who were in PR before SCT this was due to lower relapse rate among chemosensitive patients after haplo-SCT vs. HLA-id. In conclusion, haplo-SCT showed high antitumor activity, leading to promising outcome of chemosensitive patients compared with HLA-id transplants. Present data may challenge donor choice in this subset of patients, who may benefit from graft-versus-lymphoma effect, potentially enhanced by haplo disparity. No relevant conflicts of interest to declare.
Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Publisher: Massachusetts Medical Society
Date: 24-08-2023
Achievements of Hinode in the first eleven years
Publisher: Oxford University Press (OUP)
Date: 10-2019
DOI: 10.1093/PASJ/PSZ084
Abstract: Hinode is Japan’s third solar mission following Hinotori (1981–1982) and Yohkoh (1991–2001): it was launched on 2006 September 22 and is in operation currently. Hinode carries three instruments: the Solar Optical Telescope, the X-Ray Telescope, and the EUV Imaging Spectrometer. These instruments were built under international collaboration with the National Aeronautics and Space Administration and the UK Science and Technology Facilities Council, and its operation has been contributed to by the European Space Agency and the Norwegian Space Center. After describing the satellite operations and giving a performance evaluation of the three instruments, reviews are presented on major scientific discoveries by Hinode in the first eleven years (one solar cycle long) of its operation. This review article concludes with future prospects for solar physics research based on the achievements of Hinode.
Allogeneic hematopoietic stem cell transplantation in a cohort of 314 advanced lymphoma patients.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-05-2014
Quality-of-life analysis of pembrolizumab vs brentuximab vedotin for relapsed/refractory classical Hodgkin lymphoma
Publisher: American Society of Hematology
Date: 19-01-2022
DOI: 10.1182/BLOODADVANCES.2021004970
Abstract: KEYNOTE-204 (NCT02684292) demonstrated a progression-free survival advantage for pembrolizumab over brentuximab vedotin (BV) in patients who had relapsed or refractory classical Hodgkin lymphoma (R/R cHL) following, or who were ineligible for, autologous stem cell transplantation (ASCT). Health-related quality of life (HRQoL), measured by patient-reported outcomes (PROs) from KEYNOTE-204, are reported from patients who received ≥1 dose of study treatment and completed ≥1 PRO assessment. The EORTC QoL Questionnaire Core 30 (QLQ-C30) and EuroQoL EQ-5D were administered at baseline, every 6 weeks until week 24, and every 12 weeks thereafter. Prespecified end points included least squares mean (LSM) changes from baseline to week 24 and time to true deterioration (TTD ≥10-point decline from baseline). Comparisons were evaluated using 2-sided P values uncontrolled for multiplicity. High compliance at baseline (& %) and through week 24 (& %) was demonstrated across treatment groups (PRO analysis set: pembrolizumab, n = 146 BV, n = 150). The EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) score improved from baseline to week 24 on pembrolizumab and worsened on BV and demonstrated significant LSM differences at 24 weeks (GHS/QoL: 8.60 [95% confidence interval, 3.89-13.31] P = .0004). Significant improvements were observed in each QLQ-C30 domain except emotional and cognitive functioning. Compared with BV, pembrolizumab prolonged TTD for GHS/QoL (hazard ratio, 0.40 [95% CI, 0.22-0.74] P = .003) and each QLQ-C30 domain except cognitive functioning. In conclusion, pembrolizumab demonstrated overall improvements in PROs of HRQoL measures over BV in the KEYNOTE-204 study. These data and previously reported efficacy results support pembrolizumab as the preferred treatment option for patients with R/R cHL who are ineligible for or experience relapse after ASCT.
Clinical relevance of clonal hematopoiesis in persons aged ≥80 years
Publisher: American Society of Hematology
Date: 25-11-2021
Abstract: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes common in persons aged ≥80 years, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 persons aged ≥80 years and investigated the relationships between CHIP and associated pathologies. Mutations were observed in one-third of persons aged ≥80 years and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, and ASXL1 with additional genetic lesions), and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1, or JAK2 were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was common in persons aged ≥80 years, with the underlying cause remaining unexplained in 30% of cases. Among in iduals with unexplained cytopenia, the presence of highly specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordingly, 7.5% of subjects aged ≥80 years with cytopenia had presumptive evidence of myeloid neoplasm. In summary, specific mutational patterns define different risk of developing myeloid neoplasms vs inflammatory-associated diseases in persons aged ≥80 years. In in iduals with unexplained cytopenia, mutational status may identify those subjects with presumptive evidence of myeloid neoplasms.
Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma
Publisher: Massachusetts Medical Society
Date: 17-02-2022
Ceritinib inALK-Rearranged Non–Small-Cell Lung Cancer
Publisher: Massachusetts Medical Society
Date: 27-03-2014
Erratum: Familial haploidentical challenging unrelated donor Allo-SCT in advanced non-Hodgkin lymphomas when matched related donor is not available
Publisher: Springer Science and Business Media LLC
Date: 06-2015
DOI: 10.1038/BMT.2015.79
THE MULTI-THERMAL AND MULTI-STRANDED NATURE OF CORONAL RAIN
Publisher: American Astronomical Society
Date: 09-06-2015
Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair–Deficient Cancer: Results From the Phase II KEYNOTE-158 Study
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2020
DOI: 10.1200/JCO.19.02105
Abstract: Genomes of tumors that are deficient in DNA mismatch repair (dMMR) have high microsatellite instability (MSI-H) and harbor hundreds to thousands of somatic mutations that encode potential neoantigens. Such tumors are therefore likely to be immunogenic, triggering upregulation of immune checkpoint proteins. Pembrolizumab, an anti‒programmed death-1 monoclonal antibody, has antitumor activity against MSI-H/dMMR cancer. We report data from the phase II KEYNOTE-158 study of pembrolizumab in patients with previously treated, advanced noncolorectal MSI-H/dMMR cancer. Eligible patients with histologically/cytologically confirmed MSI-H/dMMR advanced noncolorectal cancer who experienced failure with prior therapy received pembrolizumab 200 mg once every 3 weeks for 2 years or until disease progression, unacceptable toxicity, or patient withdrawal. Radiologic imaging was performed every 9 weeks for the first year of therapy and every 12 weeks thereafter. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by independent central radiologic review. Among 233 enrolled patients, 27 tumor types were represented, with endometrial, gastric, cholangiocarcinoma, and pancreatic cancers being the most common. Median follow up was 13.4 months. Objective response rate was 34.3% (95% CI, 28.3% to 40.8%). Median progression-free survival was 4.1 months (95% CI, 2.4 to 4.9 months) and median overall survival was 23.5 months (95% CI, 13.5 months to not reached). Treatment-related adverse events occurred in 151 patients (64.8%). Thirty-four patients (14.6%) had grade 3 to 5 treatment-related adverse events. Grade 5 pneumonia occurred in one patient there were no other treatment-related fatal adverse events. Our study demonstrates the clinical benefit of anti–programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer. Toxicity was consistent with previous experience of pembrolizumab monotherapy.
Vertebroplasty for pain relief and spinal stabilization in multiple myeloma
Publisher: Springer Science and Business Media LLC
Date: 15-01-2010
DOI: 10.1007/S10072-009-0197-5
Abstract: Mechanical stabilization of oncological vertebral fractures with cement augmentation is the first mechanism of pain relief, with or without restoration of vertebral body height. The aim of this study was to assess the safety and efficacy of vertebroplasty for painful vertebral body fractures in patients with multiple myeloma, in each phase of the disease. The authors reviewed a consecutive group of patients with multiple myeloma who underwent vertebroplasty at our Institute between November 2003 and December 2005. Twenty-eight levels were performed on 11 patients during 14 treatment sessions. All patients suffered from intractable back pain, and presented various lesion types (with and without fractures of posterior wall, and with and without epidural disease). The preoperative median visual analog scale (VAS) score was 7. The median duration of symptoms was 1.1 months. Eight patients were ambulating with orthopaedic devices (57%) in the pre-treatment period. Improvement or complete pain relief was observed in all patients (immediately in 8 cases, and after 2 days in 6 cases). The median VAS pain score decreased to 2. There was no symptomatic procedure-related complication. There were three cases (21%) of PMMA leakage: in the disc space in one case (7%), and in the anterior spinal canal in two cases (14%). Complete removal of orthopaedic devices was obtained in five patients (36%). No new deformation or collapse of the treated vertebrae was observed during the follow-up (range 1 day-25 months). In conclusion, vertebroplasty is a safe and efficient procedure in the treatment of painful vertebral body fractures in patients with multiple myeloma, without potential contraindications, such as fractures of the posterior wall or epidural disease. We also treated three and more levels in 28% of cases in a single session without complications. Due to the early pain relief and the low complication rate, it is possible to expand the indication to vertebroplasty for the prophylactic augmentation of those vertebral bodies at risk of fracture in which significant neoplastic substitution of the body is present.
Feasibility and Efficacy of Tandem Autologous-Allogeneic Transplantation in a Cohort of 111 Patients Affected By High-Risk Hodgkin's and Non-Hodgkin's Lymphoma
Publisher: American Society of Hematology
Date: 06-12-2014
DOI: 10.1182/BLOOD.V124.21.3863.3863
Abstract: Introduction: although high-dose chemotherapy (HDC) is the golden standard for the treatment of many relapsed or refractory lymphomas, the outcome is still unsatisfactory especially in some subsets of patients with adverse prognostic features. To improve these results, we treated high-risk patients with a tandem strategy associating debulking with HDC followed by autologous stem cell transplantation (ASCT) and subsequent adoptive immunotherapy consisting in allogeneic SCT (tandem auto-allo). We report here the outcome of 111 lymphoma patients undergoing this procedure in addition, the role of two ASCT conditioning regimens is discussed. Patients and Methods: adult patients consecutively treated at two centers (Milan, Italy and Marseille, France) were included. Criteria for receiving tandem auto-allo were: refractory disease after first-line therapy, less than CR after first salvage treatment, histology of transformed follicular, mantle-, T- and NK-cell lymphoma, relapse after prior ASCT, multiple relapses. Disease evaluation was performed by using PET scan starting from 2003. Results: 111 consecutive patients with HL or NHL were transplanted from June 2002 to September 2013. Main characteristics are shown in Table 1. Median interval between ASCT and allogeneic SCT was 85 days (range: 36-235). Sixty-two patients (56%) received BEAM (8 of them without BCNU) and 46 (41%) high-dose Melphalan (HD-Mel, 100-200 mg/m2) 3 patients received other regimens. Main characteristics were not significantly different between BEAM and HD-Mel groups with the exception of the use of more alternative donor (i.e. non HLA-identical) in the HD-Mel group: 33% vs. 13%, p=0.01. Disease status before ASCT was: CR (n=47), PR (n=38), SD (n=10), PD (n=16). Grade 3-4 mucositis occurred in 49 patients (44%) and documented infections during hospital stay in 30 (27%), without differences between BEAM and HD-Mel groups, p=0.57 and p=0.14. Disease status before allogeneic SCT was: CR (n=79), PR (n=22), SD (n=5), PD (n=5). Among the 64 patients with active disease before ASCT, the overall response rate was 87% (n=56 responders) and the rate of CR was 53% (n=34), these latter adding to the 45 (out of the 47) patients in CR before ASCT nine patients (8%) progressed between ASCT and allogeneic SCT. Again, no differences were observed in terms of response among BEAM and HD-Mel group (p=0.28). Allogeneic SCT was performed after NMA (n=43), RIC (n=66) or MA (n=2) conditioning donor was either HLA-identical (n=86), MUD 9/10 (n=2), haploidentical (n=20) or cord blood (n=3). After a median follow-up of 38 months after allogeneic SCT, 3-y OS of entire cohort was 68% (95% CI: 59-77), 3-y PFS was 61% (52-70), rates of acute GvHD grade 2-4 and chronic GvHD were 28% and 38% respectively. TRM rate was 18% (n=20). Last relapse event occurred at day +853. No difference between BEAM and HD-Mel group was observed for OS (73% and 64% respectively, p=0.40) or TRM (19% and 13%, p=0.44). CR before allogeneic SCT confirms to a major prognostic factors for OS (Figure 1), whereas donor type did not significantly impact on survival (p=0.68). No survival difference was observed between HL and NHL (p=0.53). Conclusions: tandem auto-allo confirms to be a feasible and effective therapeutic strategy in those lymphoma patients whose prognosis is expected to be unsatisfactory with ASCT alone. BEAM vs. HD-Mel appeared to be similar in terms of extrahematological toxicity, disease response and survival. Disease status before allogeneic SCT confirms to be a significant prognostic factor, underlying the importance of high-dose chemotherapy followed by ASCT as further tumor shrinking before allogeneic immunotherapy in this setting of high-risk patients. Table 1. Main patients’ and transplant characteristics Variable Value % N 111 100% Pt's age (median) 44 range:16-69 Gender M 66 59% F 45 41% Disease HL 44 40% DLBCL 12 11% FL 21 19% Transf FL 9 8% MCL 9 8% MZL 1 1% T lymph 13 12% Grey zone 1 1% NK lymphoma 1 1% Indication for tandem auto-allo 1ary refractory 28 25% no CR after salvage 43 39% histology 10 9% relapse after prior ASCT 6 5% multiple relapse 24 22% Prior therapy lines (median) 2 range: 0-7 Prior radiotherapy 26 23% ASCT conditioning BEAM 54 49% EAM 8 7% HD-Mel 100 1 1% HD-Mel 140 12 11% HD-Mel 200 33 30% other 3 3% Allogeneic stem cell donor HLA-id sibling 62 56% MUD 10/10 24 22% MUD 9/10 2 2% haplo 20 18% cord blood 3 3% Figure 1. OS according to disease status after ASCT. Figure 1. OS according to disease status after ASCT. No relevant conflicts of interest to declare.
A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy
Publisher: Elsevier BV
Date: 2003
Effect of Pembrolizumab (Pembro) Monotherapy Versus Brentuximab Vedotin (BV) on Patients (Pts) with Relapsed/Refractory Classical Hodgkin Lymphoma (R/R cHL): Exploratory Analysis of the Randomized, Ph
Publisher: American Society of Hematology
Date: 05-11-2020
DOI: 10.1182/BLOOD-2020-142565
Abstract: Introduction: The open-label, international, randomized, phase 3 KEYNOTE-204 (NCT02684292) study showed that in pts with R/R cHL, the PD-1 inhibitor pembro was superior to BV and demonstrated statistically significant, clinically meaningful improvement in PFS, with safety consistent with previous reports. This post hoc exploratory analysis of KEYNOTE-204 evaluated pembro vs BV by number of prior lines of therapy. Methods: Eligible pts were aged ≥18 y, had measurable disease and ECOG PS 0 or 1, and were post−autologous stem cell transplant (auto-SCT) or ineligible for auto-SCT. Pts who were BV-naive or BV-exposed were also eligible. Pts were randomized 1:1 to pembro 200 mg IV Q3W or BV 1.8 mg/kg IV Q3W. Randomization was stratified by status after 1L therapy (primary refractory vs relapsed & mo vs relapsed ≥12 mo after end of 1L therapy) and prior auto-SCT (yes vs no). Pts in this exploratory analysis were evaluated by number of prior therapies before enrollment (1 and ≥2 prior therapies). Primary end points were PFS by blinded independent central review (BICR) per International Working Group (IWG) criteria, including clinical and imaging data after auto-SCT or allogeneic SCT (allo-SCT) and OS. Additional end points were PFS excluding clinical and imaging data after auto-SCT or allo-SCT (secondary PFS analysis), ORR and duration of response (DOR) by BICR per IWG, and safety. Results: Of 304 randomized pts, 55 (pembro, 27 BV, 28) received 1 prior therapy and 249 (pembro, 124 BV, 125) received ≥2 prior therapies. For pts with 1 prior therapy, median (range) age was 49 y (22-84) and 22 pts (40.0%) were aged ≥65 y. No pts received prior auto-SCT and 18 (32.7%) had primary refractory disease. Auto-SCT ineligibility was due to chemorefractory disease for 21 pts (38.2%) and reasons not related to chemorefractory disease (eg, age, comorbidities) for 34 pts (61.8%). 23 pts (85.2%) and 25 pts (92.6%) in the pembro and BV groups, respectively, discontinued treatment the most common reason was progressive disease. Median (range) time from randomization to data cutoff was 24.0 mo (18.7-34.8) for pembro and 23.6 mo (18.2-34.6) for BV. For the primary PFS analysis, median PFS was 16.4 mo for pembro and 8.4 mo for BV (HR 0.70 95% CI 0.031-1.59) 12 mo PFS rates were 58.9% and 37.4%, respectively. For the secondary PFS analysis, median PFS was 11.7 mo for pembro and 8.3 mo for BV (HR 0.62 95% CI 0.28-1.40). ORR was 66.7% for pembro and 53.6% for BV. Median (range) DOR for pembro was 20.7 mo (2.8-20.7) and 14.1 mo (0.0+ to 21.9) for BV. 7 pts (25.9%) and 9 pts (33.3%) in the pembro and BV groups, respectively, received subsequent auto-SCT 1 pt in the BV group received subsequent allo-SCT. 21 pts (77.8%) on pembro and 20 (74.1%) on BV experienced a treatment-related adverse event (TRAE) most common were hyperthyroidism (22.2%) for pembro and peripheral neuropathy (22.2%) for BV. 1 (3.7%) and 8 (29.6%) of pts on pembro and BV, respectively, experienced grade 3-5 TRAEs. For pts with ≥2 prior therapies median (range) age was 34 y (18-83) and 27 (10.8%) pts were aged ≥65 y. 112 pts (45.0%) received prior auto-SCT and 105 (42.2%) had primary refractory disease. Median (range) time from randomization to data cutoff was 27.1 mo (18.8-42.0) for pembro and 27.6 (18.2-42.3) for BV. 87 (71.9%) and 121 (96.8%) in the pembro and BV groups discontinued most common reason was progressive disease. For the primary PFS analysis, median PFS was 12.6 mo for pembro and 8.2 mo for BV (HR 0.66 95% CI 0.47-0.92) 12-mo PFS rates were 52.8% and 35.3%, respectively. For the secondary PFS analysis, median PFS was 12.6 mo for pembro and 8.2 mo for BV (HR 0.63 95% CI 0.45-0.88). ORR for pembro was 65.3% and 54.4% for BV. Median (range) DOR for pembro was 20.5 mo (0.0+ to 33.2+) and 11.2 mo (0.0+ to 33.9+) for BV. 23 (19.0%) and 25 (20.0%) pts in the pembro and BV groups, respectively, received subsequent auto-SCT 14 (11.6 %) and 12 (9.6%) received subsequent allo-SCT. 89 pts (73.6%) on pembro and 97 (77.6%) on BV experienced a TRAE most common were hypothyroidism (14.9%) for pembro and peripheral neuropathy (17.6%) for BV. 23.1% and 24.0% of pts on pembro and BV, respectively, experienced grade 3-5 TRAEs. Conclusion: In pts with R/R cHL, pembro monotherapy resulted in an improvement in PFS and ORR vs BV in pts regardless of number of prior therapies. In particular, these data suggest that pembro monotherapy may be a promising option as 2L+ therapy for pts with R/R cHL ineligible for auto-SCT. Kuruvilla: Bristol-Myers Squibb Company: Consultancy TG Therapeutics: Honoraria Pfizer: Honoraria Gilead: Consultancy, Honoraria AbbVie: Consultancy Karyopharm: Consultancy, Honoraria AstraZeneca Pharmaceuticals LP: Honoraria, Research Funding Novartis: Honoraria Antengene: Honoraria Merck: Consultancy, Honoraria Celgene Corporation: Honoraria Amgen: Honoraria Roche: Consultancy, Honoraria, Research Funding Janssen: Honoraria, Research Funding Seattle Genetics: Consultancy, Honoraria. Ramchandren:Seattle Genetics, Sandoz-Novartis, Pharmacyclics, an AbbVie Company, Janssen, Bristol-Myers Squibb: Consultancy Merck, Seattle Genetics, Janssen, Genentech: Research Funding. Santoro:Arqule, Sanofi: Consultancy Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau. Paszkiewicz-Kozik:Roche, Takeda, Celgene: Other: Travel, accommodations, expenses. Gasiorowski:MSD, Takeda, Novartis, AbbVie: Honoraria. Johnson:Roche/Genentech, Merck: Honoraria Roche/Genentech, Merck, Bristol-Myers Squibb, AbbVie: Consultancy AbbVie: Research Funding. Goncalves:Janssen, Takeda, Amgen, Bayer, Novartis, Merck, Bayer, Celgene, GSK, BMS: Research Funding Janssen: Consultancy, Speakers Bureau. Perini:Janssen, Takeda: Honoraria AbbVie, Janssen: Speakers Bureau. Goldschmidt:Abbvie Inc: Consultancy, Research Funding. Kryachok:Janssen, Bayer, Karyopharm, MSD, AbbVie, Acerta, Debiopharm: Research Funding Takeda, Janssen: Consultancy Takeda, MSD, AbbVie, Roche: Other: Travel, accommodations, expenses. Sekiguchi:Ono, A2 Healthcare, Astellas, Janssen, Merck Sharp & Dohme, Otsuka, Pfizer, PPD-SNBL, Sumitomo Dainippon, Daiichi Sankyo, and Bristol-Myers Squibb: Research Funding. Lin:Merck & Co., Inc.: Current Employment. Nahar:Merck Sharp & Dohme, Corp., a subsididary of Merck & Co., Inc., Kenlworth, NJ, USA: Current Employment. Marinello:Merck & Co., Inc.: Other: Travel, accommodations, expenses Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Current Employment Merck & Co., Inc., Kenilworth, NJ, USA: Other: Stock ownership. Zinzani:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau TG Therapeutics, Inc.: Honoraria, Speakers Bureau Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Janssen: Consultancy, Honoraria, Speakers Bureau EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau Eusapharma: Consultancy, Speakers Bureau Kyowa Kirin: Consultancy, Speakers Bureau Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
Tandem autologous-allogeneic stem cell transplantation as a feasible and effective procedure in high-risk lymphoma patients
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 23-07-2015
Related Organisations
Stanford University School Of Medicine
Location: United States of America
Memorial Sloan Kettering Cancer Center
Location: United States of America
University Of St Andrews
Location: United Kingdom of Great Britain and Northern Ireland
Northumbria University
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Armando Santoro.