Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Haematologica ; 109(3): 888-894, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37646655

RESUMEN

Autologous peripheral blood stem cell transplantation (aPBSCT) provides optimal outcomes in POEMS syndrome but the definition of the best treatment before aPBSCT remains to be defined because of the rarity of the disease and the heterogeneity of published case series. We collected clinical and laboratory data of patients with POEMS syndrome undergoing aPBSCT from 1998 to 2020 in ten Italian centers. The primary endpoint of the study was to evaluate the impact of prior therapies and mobilization regimen on outcome. We divided the patients into three groups: patients who did not receive any treatment before transplant (15 patients, group A: front-line), patients pre-treated with other agents (14 patients, group B) and patients treated with cyclophosphamide as their mobilizing regimen (16 patients, group C). The three groups did not show differences in terms of demographic and clinical characteristics. All 45 patients underwent aPBSCT after a high-dose melphalan conditioning regimen, with a median follow-up of 77 months (range, 37-169 months). The responses were not statistically different between the three groups (P=0.38). Progression-free and overall survival rates at 6 years were: 70% (95% confidence interval: 55-85%) and 91% (95% confidence interval: 82-99) 65%, respectively, and did not differ between the three groups. The cumulative incidence of transplant-related mortality and relapse was 4% and 36%, respectively. In conclusion, in a relatively large number of patients with POEMS syndrome, undergoing an autologous transplant, pre-treatment and disease status at transplant did not appear to have an impact on major transplant outcomes.


Asunto(s)
Síndrome POEMS , Trasplante de Células Madre de Sangre Periférica , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Trasplante Autólogo , Autoinjertos , Ciclofosfamida/uso terapéutico
2.
Haematologica ; 109(1): 245-255, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37439329

RESUMEN

In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved to have a superior clinical benefit over pomalidomide and dexamethasone with a manageable toxicity profile, leading to its approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. We report here a real-world experience of 200 cases of RRMM treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was two, with 51% of cases undergoing autologous stem cell transplant and 73% having been exposed to daratumumab. After a median follow-up of 9 months, 126 patients had stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate was 55.4%, a finding in line with the pivotal trial results. Regarding adverse events, the toxicity profile in our cohort was similar to that in the ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older patients. The median progression-free survival was 7 months, which was shorter than that observed in ELOQUENT-3, probably because of the different clinical characteristics of the two cohorts. Interestingly, International Staging System stage III disease was associated with worse progression-free survival (hazard ratio=2.55). Finally, the median overall survival of our series was shorter than that observed in the ELOQUENT-3 trial (17.5 vs. 29.8 months). In conclusion, our real-world study confirms that EloPd is a safe and possible therapeutic choice for patients with RRMM who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.


Asunto(s)
Mieloma Múltiple , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Lenalidomida/uso terapéutico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/etiología , Inhibidores de Proteasoma/uso terapéutico , Estudios Retrospectivos , Ensayos Clínicos Controlados como Asunto
3.
Hematol Oncol ; 42(4): e3290, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38818978

RESUMEN

The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiple , Talidomida , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Masculino , Femenino , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Persona de Mediana Edad , Talidomida/análogos & derivados , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/uso terapéutico , Estudios Retrospectivos , Estudios de Seguimiento , Anciano de 80 o más Años , Adulto , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Resistencia a Antineoplásicos , Tasa de Supervivencia
4.
Ann Hematol ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38805036

RESUMEN

Myeloma with extramedullary plasmacytomas not adjacent to bone (EMP) is associated with an extremely poor outcome compared with paraosseous plasmacytomas (PP) as current therapeutic approaches are unsatisfactory. The role of new molecules and in particular of monoclonal antibodies is under investigation. To determine whether daratumumab-based regimens are effective for myeloma with EMP, we report herein an initial multicenter observational analysis of 102 myeloma patients with EMP (n = 10) and PP (n = 25) at diagnosis and EMP (n = 28) and PP (n = 39) at relapse, treated with daratumumab-based regimens at 11 Haematological Centers in Italy.EMP and PP at diagnosis were associated with higher biochemical (90% vs. 96%, respectively) and instrumental ORR (86% vs. 83.3%, respectively), while at relapse, biochemical (74% vs. 73%) and instrumental (53% vs. 59%) ORR were lower. Median OS was inferior in EMP patients compared with patients with PP both at diagnosis (21.0 months vs. NR) (p = 0.005) and at relapse (32.0 vs. 40.0 months) (p = 0.428), although, during relapse, there was no statistically significant difference between the two groups. Surprisingly, at diagnosis, median TTP and median TTNT were not reached either in EMP patients or PP patients and during relapse there were no statistically significant differences in terms of median TTP (20 months for two groups), and median TTNT (24 months for PP patients vs. 22 months for EMP patients) between the two groups. Median TTR was 1 month in all populations.These promising results were documented even in the absence of local radiotherapy and in transplant-ineligible patients.

5.
Eur J Haematol ; 2024 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-39370303

RESUMEN

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.

6.
Hematol Oncol ; 40(4): 704-715, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35608183

RESUMEN

The combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 36 months (range 6-55), 236 patients experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyses showed a significant reduction of PFS and OS benefit magnitude only in cases with International Staging System stage III. Major adverse events included grade 3/4 neutropenia (18.5%), anemia (15.4%), lymphocytopenia (12.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 33.9% and 18.9%, respectively. No new safety signals with longer follow-up have been observed. Of 319 patients, 245 (76.7%) reached at least a partial remission. A significantly lower response rate was found in patients previously exposed to lenalidomide. In conclusion, our study confirms that EloRd is a safe and effective regimen for RRMM patients, maintaining benefits across multiple unfavorable subgroups.


Asunto(s)
Mieloma Múltiple , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/efectos adversos , Estudios de Seguimiento , Humanos , Lenalidomida/uso terapéutico , Estudios Retrospectivos , Talidomida/efectos adversos
7.
Eur J Haematol ; 108(3): 178-189, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34716957

RESUMEN

The lack of a randomized trial comparing carfilzomib (K) versus elotuzumab (Elo) associated with lenalidomide and dexamethasone (Rd) prompted us to assess the relative usefulness of one triplet over the other. Five independent retrospective cohorts of 883 relapsed/refractory multiple myeloma (RRMM) patients, including 300 EloRd and 583 KRd cases, outside clinical trials, entered this non-randomized comparison. KRd cohort accounted for a higher incidence of younger patients, cases with ≥3 lines of therapy, already exposed to lenalidomide, International Staging System (ISS) stage III, and abnormal lactic dehydrogenase (LDH) level compared with EloRd cohort. Moreover, cytogenetic risk categories, detected in roughly one-third of cases, were equally distributed between the two therapy arms. The probability of CR+VGPR response was significantly higher in KRd (n = 314, 53.9%) than in EloRd patients (n = 111, 37.0%). Likewise, the cumulative incidence function of CR+VGPR, taking into account the competitive risk of death, was significantly higher in KRd arm patients than those in the EloRd arm (p = .003). Moreover, KRd treatment significantly reduced the progression or death risk by 46% in an adjusted multivariate analysis (HR: 0.54, 95% CI 0.42-0.69, p < .0001). Finally, in an adjusted illness-progression/death model, the effect of KRd versus EloRd was of higher magnitude among those who achieved CR+VGPR (-39% hazard ratio reduction, p = .02) than among those who achieved < VGPR (-29% hazard ratio reduction, p = .007). With limitations characteristic to any retrospective analysis, this current clinical practice study's overall results demonstrated potential benefits of KRd therapy compared with EloRd. This observation may help the daily clinical practice.


Asunto(s)
Mieloma Múltiple , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona , Humanos , Lenalidomida , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos , Estudios Retrospectivos , Terapia Recuperativa
8.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36362130

RESUMEN

The treatment landscape for hematologic malignancies has changed since the recent approval of highly effective chimeric antigen receptor T-cell therapies (CAR-T). Moreover, more than 600 active trials are currently ongoing. However, early enthusiasm should be tempered since several issues are still unsolved and represent the challenges for the coming years. The lack of initial responses and early relapse are some hurdles to be tackled. Moreover, new strategies are needed to increase the safety profile or shorten the manufacturing process during CAR-T cells therapy production. Nowadays, most clinically evaluated CAR-T cells products are derived from autologous immune cells. The use of allogeneic CAR-T cells products generated using cells from healthy donors has the potential to change the scenario and overcome many of these limitations. In addition, CAR-T cells carry a high price tag, and there is an urgent need to understand how to pay for these therapies as many of today's current payment systems do not feature the functionality to address the reimbursement gap. Finally, the clinical experience with CAR-T cells for solid tumors has been less encouraging, and development in this setting is desirable.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inmunoterapia Adoptiva , Neoplasias/tratamiento farmacológico , Tratamiento Basado en Trasplante de Células y Tejidos
9.
Medicina (Kaunas) ; 57(8)2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34441031

RESUMEN

Background and Objectives: The purpose of this study was to evaluate the feasibility, safety and efficacy of microwave ablation (MWA) in combination with open surgery nail positioning for the treatment of fractures or impending fractures of long bone metastases. Material and Methods: Eleven patients (four men, seven women) with painful bone metastases of the humerus, femur or tibia with non-displaced fractures (one case) or impending fractures (10 cases) underwent open MWA in combination with osteosynthesis by locked nail positioning. Pain intensity was measured using a VAS score before and after treatment. CT or MRI were acquired at one month before and 1, 3, 6, 12 and 18 months after treatment. Results: All procedures were successfully completed without major complications. The level of pain was significantly reduced one month after treatment. For the patients with humerus metastases, the complete recovery of arm use took 8 weeks, while for the patients with femoral metastases the complete recovery of walking capacity took 11 weeks. The VAS score ranged from 7 (4-9) before treatment to 1.5 (0-2.5) after treatment. During a mid-term follow-up of 18 months (range 4-29 months), none of the patients showed tumor relapse or new fractures in the treated site. Two patients died due to tumor disease progression. Conclusion: Results of this preliminary study suggest that combined MWA and surgical osteosynthesis with locked nails is a safe and effective treatment for pathological fractures or malignant impending fractures of long bone metastases of the humerus, femur and tibia. Further analyses with larger cohorts are warranted to confirm these findings.


Asunto(s)
Neoplasias Óseas , Microondas , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugía , Femenino , Fijación Interna de Fracturas , Humanos , Masculino , Microondas/uso terapéutico , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Resultado del Tratamiento
10.
Haematologica ; 106(1): 291-294, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-32107338
11.
Hematol Oncol ; 34(1): 17-21, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25626861

RESUMEN

In recent years, with the aim of reducing transplant-related mortality, new conditioning regimens have been explored in patients not eligible for conventional haemopoietic stem cell transplantation. In this setting, we investigated safety and feasibility of the treosulfan-fludarabine-thiotepa combination prior to allogeneic haemopoietic stem cell transplantation in patients with advanced lympho-proliferative diseases and at high transplant risk. Twenty-seven consecutive patients, median age 43 years (range 19-60), entered this study. All of them were affected by lympho-proliferative disease in advanced phase and have been heavily pre-treated. The median haemopoietic stem cell transplant co-morbidity index was 1 (range 0-3). Twenty-five patients had regular engraftment, while the remaining two patients were not evaluable for early deaths. Non-haematological toxicity was limited. No patient developed veno-occlusive disease. The estimated probability of overall survival and progression-free survival with a median follow-up of 40 months was 52% (95% confidence interval 33-73) and 50% (95% confidence interval 30-70) respectively. Six patients have relapsed; all of them were not in remission before transplantation. The treosulfan-fludarabine-thiotepa combination is a reduced toxicity but myeloablative regimen that can be proposed to patients not fitting criteria for conventional myeloablative transplant regimens. Longer follow-up and prospective randomized studies are necessary to evaluate this regimen.


Asunto(s)
Trasplante de Médula Ósea , Busulfano/análogos & derivados , Neoplasias Hematológicas/terapia , Trasplante de Células Madre de Sangre Periférica , Terapia Recuperativa , Tiotepa/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Adulto , Busulfano/efectos adversos , Busulfano/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/mortalidad , Recurrencia , Inducción de Remisión , Tiotepa/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo , Trasplante Homólogo/mortalidad , Resultado del Tratamiento , Vidarabina/efectos adversos , Vidarabina/uso terapéutico , Adulto Joven
12.
Blood ; 120(1): 9-19, 2012 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-22498745

RESUMEN

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Ácidos Borónicos/administración & dosificación , Bortezomib , Terapia Combinada , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunosupresores/administración & dosificación , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Pronóstico , Pirazinas/administración & dosificación , Talidomida/administración & dosificación , Trasplante Autólogo
13.
J Pathol ; 229(1): 87-98, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22847671

RESUMEN

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high affinity and selectivity to fibroblast growth factor-2 (FGF2), thus inhibiting its pro-angiogenic activity. Here we investigated the effects of PTX3 on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patient-derived bone marrow (BM) plasma cells (PCs), endothelial cells (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross-talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was evaluated by ELISA. Functional studies, including cell viability, wound healing, chemotaxis, and Matrigel(®) assays, were performed on MGUS and MM ECs and FBs upon the PTX3 treatment. Through western blot PTX3-induced modulation in FGF2/FGF receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through western blot. Co-cultures between MM ECs/FBs and human PC lines were used to evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were studied by flow cytometry. PTX3 provides a direct time- and dose-dependent apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC lines. PTX3 inhibits migration of MM ECs and FBs in a dose-dependent manner, and impacts in vitro and in vivo FGF2-mediated MM angiogenesis. Co-cultures of PCs and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and adhesion. We conclude that PTX3 is an anti-angiogenic factor in MM and behaves as a cytotoxic molecule on MM cells by inhibiting the cross-talk between PCs and ECs/FBs.


Asunto(s)
Células de la Médula Ósea/metabolismo , Proteína C-Reactiva/metabolismo , Comunicación Celular , Células Endoteliales/metabolismo , Fibroblastos/metabolismo , Mieloma Múltiple/metabolismo , Células Plasmáticas/metabolismo , Componente Amiloide P Sérico/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Apoptosis , Western Blotting , Células de la Médula Ósea/patología , Estudios de Casos y Controles , Adhesión Celular , Moléculas de Adhesión Celular/metabolismo , Línea Celular , Microambiente Celular , Quimiotaxis , Embrión de Pollo , Técnicas de Cocultivo , Medios de Cultivo Condicionados/metabolismo , Citocinas/metabolismo , Células Endoteliales/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibroblastos/patología , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/metabolismo , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/irrigación sanguínea , Mieloma Múltiple/patología , Neovascularización Patológica , Células Plasmáticas/patología , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal , Factores de Tiempo , Células Tumorales Cultivadas
14.
Pharmaceuticals (Basel) ; 17(8)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39204135

RESUMEN

Renal failure is one of the most important manifestations of multiple myeloma. It is caused by renal lesions such as cast nephropathy, immunoglobulin deposition disease, AL amyloidosis or other glomerular and/or tubular diseases, mostly due to the toxic effect of free light chains in serum. Renal failure can represent a clinical emergency and is associated with poor outcome in newly diagnosed and relapsed/refractory multiple myeloma patients. Although progression-free survival and overall survival have improved with the introduction of novel agents, renal failure remains a challenge for the treatment of patients with multiple myeloma. Monoclonal antibodies are a component of therapy for newly diagnosed and relapsed/refractory patients and, based on clinical trials and real-world experience, are also safe and effective for subjects with renal failure, even if they are on dialysis. Most of the data are on anti-CD38 and anti-SLAM7 antibodies, but new antibody-drug conjugates such as belantamab mafodotin and bispecific antibodies also appear to be effective in myeloma kidney disease. In the future, we will have to face some challenges, such as defining new criteria for renal response to treatment, defining specific trials for these difficult-to-treat patients and integrating different therapeutic options.

15.
EJHaem ; 5(3): 485-493, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38895069

RESUMEN

Belantamab mafodotin is the first-in-class antibody-drug conjugates targeting B-cell maturation antigen to have demonstrated effectiveness in triple-class refractory multiple myeloma (TCR-MM) patients. We performed a retrospective study including 78 TCR patients, with at least four prior lines of therapy (LOTs), who received belantamab mafodotin within named patient program and expanded access program in Italy between 2020 and 2022. Median age was 65 years (range 42-86 years), ECOG performance status was ≥1 in 45% of patients. Overall, a clinical benefit was obtained in 36 out of 74 evaluable patients (49%), with 43%, 28%, and 13.5% achieving at least partial response, very good partial response, and complete response, respectively. After a median follow-up of 12 months (range 6-21 months), median duration of response, progression-free survival (PFS), and overall survival (OS) were 14, 5.5, and 12 months, respectively. Age >70 years, good performance status and response were associated with longer PFS and OS. Keratopathy occurred in 58% of patients (G3 2.5%), corneal symptoms in 32% (G3 1.2%) and a reduction in visual acuity in 14%. Grade 3 thrombocytopenia occurred in 9% of patients. Only 3% of patients discontinued belantamab mafodotin because of side effects. This real-life study demonstrated significant and durable responses of belantamab in TCR-MM patients with four prior LOTs, otherwise ineligible for novel immunotherapies.

16.
Front Surg ; 10: 1121981, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37288134

RESUMEN

Objective: To retrospectively evaluate the feasibility and effectiveness of vertebroplasty using Spinejack implantation for the treatment and stabilization of painful vertebral compression fractures, in patients diagnosed with Multiple Myeloma (MM), to allow both an effective pain reduction and a global structural spine stabilization. Materials and Methods: From July 2017 and May 2022 thirty-nine patients diagnosed MM, with forty-nine vertebral compression fractures underwent percutaneous Vertebroplasty using Spinejack Implants. We analyzed the feasibility and complications of the procedure, the decrease in pain using visual analogue scale (VAS) and Functional Mobility Scale (FMS). Results: The technical success rate was 100%. No procedure-related major complications or death occurred. In the 6-month follow-up, the mean VAS score decreased from 5.4 ± 1.0 to 0.2 ± 0.5 with a mean reduction of 96.3%. FMS decreased from 2.3 ± 0.5 vs. 1.2 ± 0.4 with a mean reduction of -47.8%. There were no major complications related to incorrect positioning of the Expandable Titanium SpineJack Implants. In five patients, a cement leak was observed with no associated clinical manifestations. The average length of hospital stay was 6-8 Hours6.6 ± 1.2 h. No new bone fractures or local disease recurrence occurred during a median contrast-enhanced CT follow-up of 6 months. Conclusions: Our results suggest that vertebroplasty, using Spinejack implantation for the treatment and stabilization of painful vertebral compression fractures, secondary to Multiple Myeloma is a safe and effective procedure with long - term pain relief and restoration of vertebral height.

17.
G Ital Nefrol ; 40(Suppl 81)2023 Oct 03.
Artículo en Italiano | MEDLINE | ID: mdl-38007837

RESUMEN

Monoclonal Gammopathies of Renal Significance (MGRS) are a complex group of disorders characterized by the production of aberrant monoclonal proteins that interact with kidney structures, causing tissue damage. Unlike neoplastic forms, kidney damage in MGRS does not correlate with clone mass or circulating monoclonal protein levels, conferring unique pre-neoplastic or non-neoplastic properties to the responsible clones. This manuscript explores the heterogeneity of monoclonal proteins involved, varying from full immunoglobulins to free light chains (FLC), and how they result in a spectrum of kidney lesions with differing prognoses. We also elaborate on diagnostic challenges, emphasizing the indispensable role of kidney biopsy, including advanced techniques like laser microdissection and mass spectrometry (LMD/MS) for deposit characterization, particularly in ambiguous or complex cases. Clinical management and treatment considerations, including the necessity for clone identification, are also discussed.


Asunto(s)
Enfermedades Renales , Paraproteinemias , Humanos , Paraproteinemias/diagnóstico , Paraproteinemias/terapia , Enfermedades Renales/diagnóstico , Enfermedades Renales/etiología , Enfermedades Renales/terapia , Riñón/patología , Cadenas Ligeras de Inmunoglobulina , Anticuerpos Monoclonales
18.
Curr Oncol ; 30(2): 1663-1672, 2023 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-36826088

RESUMEN

(1) Background: The aim of this study was to retrospectively evaluate the safety and efficacy of a combined CT-guided percutaneous microwave ablation (MWA) and pedicle screw fixation followed by vertebroplasty (MASFVA) for the treatment and stabilization of painful vertebral metastases with vertebral pedicle involvement. (2) Methods: from January 2013 to January 2017 11 patients with 16 vertebral metastatic lesions (7 men and 5 women; mean age, 65 ± 11 years) with vertebral metastases underwent CT-guided microwave ablation and screw fixation followed by vertebroplasty (MASFVA). Technical success, complication rate, pain evaluation using a visual analogue scale (VAS), Oswestry Disability Index (ODI) and local tumor control were examined. (3) Results: Technical success rate was 100%. No procedure-related major complications occurred. VAS score decreased from 6.8 ± 0.7 to 0.6 ± 0.6. ODI score decreased from 3.1 ± 0.7 to 1.2 ± 0.4. All patients could walk independently without neurological complication after one week from the procedure. No new bone fractures or local disease recurrence occurred during a median follow-up of 12 months. (4) Conclusions: Our results suggest that MWA and percutaneous pedicle screw fixation followed by vertebroplasty for the treatment of painful vertebral metastases is a safe and effective procedure for painful vertebral metastases with vertebral pedicle involvement, allowing pain relief and local tumor control.


Asunto(s)
Tornillos Pediculares , Fracturas de la Columna Vertebral , Vertebroplastia , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Cuerpo Vertebral , Microondas , Vértebras Lumbares/lesiones , Vértebras Lumbares/cirugía , Vértebras Torácicas/lesiones , Vértebras Torácicas/cirugía , Fracturas de la Columna Vertebral/cirugía , Resultado del Tratamiento , Vertebroplastia/métodos , Dolor , Tomografía Computarizada por Rayos X
19.
Curr Oncol ; 30(4): 4257-4268, 2023 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-37185437

RESUMEN

(1) Background: Cement distribution after radiofrequency ablation of spinal metastases can be unpredictable due to various tumor factors, and vertebral augmentation requires advanced devices to prevent cement leakage and achieve satisfactory filling. The purpose of this study is to evaluate the safety and efficacy of a platform of steerable technologies with an articulating radiofrequency ablation (RFA) probe and targeted cavity creation before vertebral augmentation in the treatment of painful spinal metastases. (2) Methods: Sixteen patients (mean age, 67 years) underwent RFA in conjunction with vertebral augmentation after the creation of a targeted balloon cavity for metastatic spinal disease and were followed up to 6 months. Pain and functional mobility were assessed before treatment and postoperatively using the Visual Analogue Score (VAS) and Functional Mobility Scale (FMS). Complications, predictability of cement distribution, anatomical restoration, and local recurrence were collected. Technical success was defined as successful intraoperative ablation and predictable cement distribution after cavity creation without major complications. (3) Results: Sixteen patients with 21 lesions were treated for tumors involving the thoracolumbar spine. All treatments were technically successful and were followed by targeted cavity creation and vertebral augmentation. A statistically significant reduction in median VAS score was observed before treatment and 1 week after RFA treatment (p < 0.001). A total of six of the seven patients who reported limited painful ambulation before treatment reported normal ambulation 1 month after treatment, while the remaining patient reported no improvement. Patients who reported wheelchair use before treatment improved to normal ambulation (four/eight) or limited painful ambulation (four/eight). The improvement in mobility before and after treatment was statistically significant (p = 0.002). Technical success was achieved in all the combined procedures. (4) Conclusions: The combined treatment of RFA and vertebral augmentation with a steerable platform that allows the creation of a targeted cavity prior to cement injection proved to be a safe and effective procedure in our patient sample, resulting in improved quality of life as assessed by the Visual Analogue Score (VAS) and Functional Mobility Scale (FMS).


Asunto(s)
Ablación por Catéter , Ablación por Radiofrecuencia , Neoplasias de la Columna Vertebral , Humanos , Anciano , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/secundario , Calidad de Vida , Ablación por Catéter/métodos , Dolor
20.
J Clin Med ; 12(13)2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37445213

RESUMEN

(1) Background: to retrospectively evaluate safety and efficacy of combined microwave ablation (MWA) and bilateral expandable titanium SpineJack (SJ) implants followed by vertebroplasty (VP) for the treatment of painful thoracolumbar pathological vertebral compression fracture. (2) Methods: from July 2017 to October 2022, twenty-eight patients (13 women and 15 men; mean age 68 ± 11 years) with a history of primary neoplasm and thirty-six painful vertebral metastases with vertebral compression fracture underwent combined MWA and bilateral expandable titanium SpineJack implants with vertebroplasty. We analyzed safety through complications rate, and efficacy through vertebral height restoration and pain decrease, evaluated using a visual analogue scale (VAS), and Functional Mobility Scale (FMS), and local tumor control. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI at 6 months after the procedure. (3) Results: Technical success rate was 100%. No procedure-related major complications or death occurred. Vertebral height restoration was observed in 22 levels (58%), with a mean anterior height restoration of 2.6 mm ± 0.6 and a mean middle height restoration of 4.4 mm ± 0.6 (p < 0.001). Mean VAS score of pain evaluation on the day before treatment was 6.3 ± 1.5 (range 4-9). At the 6-month evaluation, the median VAS score for pain was 0.4 ± 0.6 (range 0-2) with a mean reduction of 93.65% (6.8 ± 0.7 vs. 0.4 ± 0.6; p < 0.000) compared with baseline evaluation. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI was performed at 6 months after the procedure, showing no local recurrence, implant displacement, or new fractures in the treated site. (4) Conclusions: combined microwave ablation and bilateral expandable titanium SpineJack implants with vertebroplasty is a safe and effective procedure for the treatment of pathological compressive vertebral fractures. The vertebral stabilization achieved early and persistent pain relief, increasing patient mobility, improving recovery of walking capacity, and providing local tumor control.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA