RESUMO
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.
Assuntos
Mieloma Múltiplo , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Lenalidomida/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/etiologia , Inibidores de Proteassoma/uso terapêutico , Estudos Retrospectivos , Ensaios Clínicos Controlados como AssuntoRESUMO
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.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiplo , Talidomida , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Masculino , Feminino , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pessoa de Meia-Idade , Talidomida/análogos & derivados , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Estudos Retrospectivos , Seguimentos , Idoso de 80 Anos ou mais , Adulto , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Resistencia a Medicamentos Antineoplásicos , Taxa de SobrevidaRESUMO
In multiple myeloma (MM) bone marrow infiltration by monoclonal plasma cells can occur in both focal and diffuse manner, making staging and prognosis rather difficult. The aim of our study was to test whether texture analysis of 18 F-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) images can predict survival in MM patients. Forty-six patients underwent 18 F-FDG-PET/CT before treatment. We used an automated contouring program for segmenting the hottest focal lesion (FL) and a lumbar vertebra for assessing diffuse bone marrow involvement (DI). Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and texture features such as Coefficient of variation (CoV), were obtained from 46 FL and 46 DI. After a mean follow-up of 51 months, 24 patients died of myeloma and were compared to the 22 survivors. At univariate analysis, FL SUVmax (p = 0.0453), FL SUVmean (p = 0.0463), FL CoV (p = 0.0211) and DI SUVmax (p = 0.0538) predicted overall survival (OS). At multivariate analysis only FL CoV and DI SUVmax were retained in the model (p = 0.0154). By Kaplan-Meier method and log-rank testing, patients with FL CoV below the cut-off had significantly better OS than those with FL CoV above the cut-off (p = 0.0003), as well as patients with DI SUVmax below the threshold versus those with DI SUVmax above the threshold (p = 0.0006). Combining FL CoV and DI SUVmax by using their respective cut-off values, a statistically significant difference was found between the resulting four survival curves (p = 0.0001). Indeed, patients with both FL CoV and DI SUVmax below their respective cut-off values showed the best prognosis. Conventional and texture parameters derived from 18F-FDG PET/CT analysis can predict survival in MM patients by assessing the heterogeneity and aggressiveness of both focal and diffuse infiltration.
Assuntos
Fluordesoxiglucose F18 , Mieloma Múltiplo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/mortalidade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Prognóstico , Idoso de 80 Anos ou mais , Adulto , Seguimentos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Taxa de SobrevidaRESUMO
The reliability and safety of front-line ultrasonography guided core needle biopsy (UG-CNB) performed with specific uniform approach have never been evaluated in a large series of patients with lymphadenopathies suspected of lymphoma. The aim of this study was to assess the overall accuracy of UG-CNB in the lymph node histological diagnosis, using a standard reference based on pathologist consensus, molecular biology, and/or surgery. We retrospectively checked the findings concerning the application of lymph node UG-CNB from four Italian clinical units that routinely utilized 16-gauge diameter modified Menghini needle under power-Doppler ultrasonographic guidance. A data schedule was sent to all centers to investigate the information regarding techniques, results, and complications of lymph node UG-CNB in untreated patients over a 12-year period. Overall, 1000 (superficial target, n = 750; deep-seated target, n = 250) biopsies have been evaluated in 1000 patients; other 48 biopsies (4.5%), screened in the same period, were excluded because inadequate for a confident histological diagnosis. Most patients were suffering from lymphomas (aggressive B-cell non-Hodgkin lymphoma [aBc-NHL], 309 cases; indolent B-cell [iBc]-NHL, 279 cases; Hodgkin lymphoma [HL], 212 cases; and nodal peripheral T-cell [NPTC]-NHL, 30 cases) and 100 cases from metastatic carcinoma; 70 patients had non-malignant disorders. The majority of CNB results met at least one criterion of the composite reference standard. The overall accuracy of the micro-histological sampling was 97% (95% confidence interval: 95%-98%) for the series. The sensitivity of UG-CNB for the detection of aBc-NHL was 100%, for iBc-NHL 95%, for HL 93%, and for NPTC-NHL 90%, with an overall false negative rate of 3.3%. The complication rate was low (6% for all complications); no patient suffered from biopsy-related complications of grade >2 according to the Common Terminology Criteria for Adverse Events. Lymph node UG-CNB as mini-invasive diagnostic procedure is effective with minimal risk for the patient.
Assuntos
Doença de Hodgkin , Linfadenopatia , Linfoma , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Linfoma/diagnóstico por imagem , Linfoma/patologia , Linfadenopatia/diagnóstico , Ultrassonografia , Doença de Hodgkin/diagnóstico por imagem , Biópsia por Agulha/métodos , Itália , Biópsia com Agulha de Grande Calibre/métodosRESUMO
We evaluated the impact of liposomal doxorubicin (NPLD) supercharge-containing therapy on interim fluorodeoxyglucose positron emission tomography (interim-FDG-PET) responses in high-risk diffuse large B-cell lymphoma (DLBCL) or classical Hodgkin lymphoma (c-HL). In this phase II study (2016-2021), 81 adult patients with advanced-stage DLBCL (n = 53) and c-HL (n = 28) received front-line treatment with R-COMP-dose-intensified (DI) and MBVD-DI. R-COMP-DI consisted of 70 mg/m2 of NPLD plus standard rituximab, cyclophosphamide, vincristine and prednisone for three cycles (followed by three cycles with NPLD de-escalated at 50 mg/m2 ); MBVD-DI consisted of 35 mg/m2 of NPLD plus standard bleomycin, vinblastine and dacarbazine for two cycles (followed by four cycles with NPLD de-escalated at 25 mg/m2 ). Patients underwent R-COMP-DI and MBVD-DI with a median dose intensity of 91% and 94% respectively. At interim-FDG-PET, 72/81 patients (one failed to undergo interim-FDG-PET due to early death) had a Deauville score of ≤3. At end of treatment, 90% of patients reached complete responses. In all, 20 patients had Grade ≥3 adverse events, and four of them required hospitalisation. At a median 21-months of follow-up, the progression-free survival of the entire population was 77.3% (95% confidence interval 68%-88%). Our data suggest that the NPLD supercharge-driven strategy in high-risk DLBCL/c-HL may be a promising option to test in phase III trials, for improving negative interim-FDG-PET cases incidence.
Assuntos
Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Etoposídeo , Fluordesoxiglucose F18/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/etiologia , Estadiamento de Neoplasias , Polietilenoglicóis , Prednisona , Rituximab , Vincristina/efeitos adversosRESUMO
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.
Assuntos
Doença de Hodgkin/patologia , Adulto , Idoso , Terapia Combinada/efeitos adversos , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: In this prospective study, the impact of granulocyte colony-stimulating factors (G-2 CSF) administered during induction treatment with bendamustine plus rituximab for indolent non- Hodgkin Llymphoma (NHL) was evaluated by comparing patients who received secondary prophylaxis with filgrastim (control group) versus. patients who received pegfilgrastim as primary prophylaxis (peg-group). The primary endpoint was the incidence rate of febrile neutropenia (FN)- related chemotherapy disruptions (regarding dose-dense and/or dose-intensity of schedule). The Ssecondary endpoint included days of hospitalization due to FN, and G-CSF-related side effects (grade ≥3 WHO toxicity criteria) in each group. METHODS: One hundred twenty-two: 122 consecutive patients, with untreated indolent NHL, were referred to our outpatient unit for remission induction immuno-chemotherapy with bendamustine-rituximab. During the first period, 61 patients received secondary prophylaxis with filgrastim, given "on demand" if ANC was <1000/mm3. During the second period, 61 patients received primary prophylaxis with pegfilgrastim in a single administration. RESULTS: Pegfilgrastim was significantly associated with fewer incidence rate of FN-related chemotherapy disruptions (11.4% in the control group vs. 1.6% in the peg-group, p = 0.04) and fewer days of hospitalization due to FN (median number 18 days in the control group vs. 6 in the peg-group, p = 0.04). In terms of G-CSF-related extra-hematological grade III side effects, no significant difference has been found in the two groups (9.8% in the control group vs. 11.5% in the peg-group, p = 0.77). Only one patient stopped the treatment in the peg-group due to intolerance. CONCLUSIONS: In patients with indolent NHL, in front-line treatment with bendamustine plus rituximab, primary prophylaxis with pegfilgrastim seems to reduce the incidence of chemotherapy disruptions due to FN, and the days of hospitalization. Moreover, it is well- tolerated and may increase the opportunity to maintain the planned schedule of treatment. These results make pegfilgrastim an advantageous option in most cases both in terms of cost-effectiveness and quality of life. These preliminary observations need to be validated by controlled clinical trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Feminino , Filgrastim/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Estudos Prospectivos , Qualidade de Vida , Proteínas Recombinantes/uso terapêutico , Rituximab/administração & dosagem , Rituximab/efeitos adversosRESUMO
In this study, we compared intravenous immunoglobulins (IVIG) and subcutaneous immunoglobulins (SCIG) in terms of serum IgG concentration and incidence of infections in patients with hypogammaglobulinemia secondary to chemo-immunotherapy regimens including the anti-CD20 monoclonal antibody rituximab. Fourteen patients with a B-cell lymphoproliferative disease treated for at least six months with a rituximab-including chemo-immunotherapy regimen were recruited. Mean serum levels of IgG were higher during replacement therapy than at the end of rituximab treatment (p<0.001). Moreover, serum IgG level was higher during replacement therapy with SCIG than with IVIG (p<0.001). No differences in the incidence of infections were observed. Although the non-randomized design and the small number of patients do not allow definitive conclusions to be drawn, study results suggest that higher mean serum IgG levels are reached when using the subcutaneous route after a switch from the intravenous regimen, and that IVIG and SCIG offer comparable protection against infections.
Assuntos
Agamaglobulinemia/sangue , Agamaglobulinemia/tratamento farmacológico , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Agamaglobulinemia/induzido quimicamente , Idoso , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Esquema de Medicação , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/efeitos adversos , Infusões Intravenosas , Infusões Subcutâneas , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Rituximab/efeitos adversos , Resultado do TratamentoAssuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/prevenção & controle , Lamivudina/uso terapêutico , Linfoma Difuso de Grandes Células B/virologia , Tenofovir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite B Crônica/complicações , Humanos , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Ativação Viral/efeitos dos fármacos , Adulto JovemRESUMO
PURPOSE: Chronic disseminated candidiasis (CDC) is a complication of Candida infection in immunocompromised patients, involving the liver and spleen, and rarely other organs. The aim of the study is to identify the best antifungal drug for hematologic immunocompromised patients with CDC. METHODS: In this multicentric retrospective study, the charts of 20 patients with CDC following cytotoxic agent protocols for hematological malignancies, diagnosed from 2003 to 2013, were analyzed. The response to systemic antifungal therapy within 90 days from CDC diagnosis and the possible delay in chemotherapy plan, due to the infection, were evaluated. RESULTS: Six patients were treated with high-dose (HD; 5 mg/kg/daily) liposomal amphotericin B (L-AmB), whereas three received standard-dose (SD) L-AmB (3 mg/kg/daily). Azoles were given to six patients; the remaining five were treated with echinocandins. All patients treated with HD L-AmB (6/6-100 %) achieved complete resolution of CDC; one of them had to interrupt the chemotherapy program for the infection. In the SD L-AmB group, treatment failed in the 100 % of cases and one patient had to delay chemotherapy for the infection. Of the six patients who received azoles, two achieved complete resolution of the infection, four experienced treatment failure, and only three performed chemotherapy as planned. Echinocandins treatment resulted in complete resolution of the infection in 2/5 cases, partial response in 2/5 cases, and failure in one case. In this group, 3/5 patients completed chemotherapy as planned. CONCLUSIONS: This study shows that HD L-AmB was particularly effective against CDC in hematologic patients, allowing most patients to continue cytotoxic agent program.
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Neoplasias Hematológicas/complicações , Adulto , Anfotericina B/administração & dosagem , Candidíase/etiologia , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Longitudinal strain is an early marker of left ventricular (LV) dysfunction in several cardiac diseases. Our aim was to differentiate cardiac amyloidosis (CA) at diagnosis from hypertensive LV hypertrophy (LVH) by analysis of longitudinal myocardial deformation. METHODS: Thirty healthy controls (C), 30 newly diagnosed, never treated hypertensives with LVH (H-LVH), and 33 patients with CA at diagnosis underwent echo Doppler including speckle tracking-based automated function imaging (AFI). Averaged peak systolic global longitudinal strain (GLS, 18 segments) and basal, middle, and apical longitudinal strain (BLS, MLS, and ALS, respectively, six segments each) were calculated. RESULTS: Left ventricular mass index, relative wall thickness, and ejection fraction did not differ between H-LVH and CA. E/e' ratio was higher in CA than in H-LVH (P<.001) and C (P<.0001). GLS was lower in CA than in C (P<.0001), without difference with H-LVH. ALS did not differ among the three groups, MLS was significantly lower in both CA and H-LVH than in C but BLS was lower in CA compared to both H-LVH and C (both P<.0001). In the pooled population, E/e' was independently associated with BLS (ß=-0.54, P<.0001). At receiver operating curve analysis, CA was predicted by BLS≤-11.3% (sensitivity=63.3%, specificity=100%) and E/e'≥12.3 (sensitivity=69.7%, specificity=83.3%). The best AUC (=0.819) was obtained by the combination E/e'+BLS. CONCLUSIONS: Our findings highlight a real difference of E/e' ratio and longitudinal strain of LV basal segments between hypertensive LVH and CA, which could be used to differentiate the two diseases.
Assuntos
Amiloidose/fisiopatologia , Ventrículos do Coração/fisiopatologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Amiloidose/complicações , Amiloidose/diagnóstico por imagem , Diagnóstico Diferencial , Ecocardiografia/métodos , Módulo de Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologiaRESUMO
INTRODUCTION: Therapeutic strategies against multiple myeloma (MM) have evolved dramatically in recent decades, with unprecedent results in the treatment landscape, culminating in the recent incorporation of novel agents in the anti-myeloma armamentarium. AREAS COVERED: BCMA represents one of the most promising targets in MM and currently available immune approaches, either approved or under active investigation, are clearly showing their greater potential over standard regimens. In this context, immunotherapies based on chimeric antigen receptor (CAR)-engineered T-cells and bispecific antibodies (BsAbs) have taken center stage, being the ones that are yielding the most promising results in clinical trials. This review focuses on the current landscape of BsAbs and CAR-T, summarizing the latest advances and possible future developments. EXPERT OPINION: CAR-T and BsAbs anti-BCMA strategies represent breakthrough therapies against MM. However, their inclusion in clinical practice is almost feared, due to the associated limitations, some of which have been addressed here. Meanwhile, all the efforts should be focused on individualizing and choosing the most suitable candidates for each treatment and to understand how to combine, or sequence, these therapies to improve efficacy and minimize toxicity, especially for those patients with limited available treatment options.
Assuntos
Anticorpos Biespecíficos , Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Anticorpos Biespecíficos/uso terapêutico , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/imunologia , Antígeno de Maturação de Linfócitos B/imunologia , Antígeno de Maturação de Linfócitos B/antagonistas & inibidores , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/uso terapêutico , Imunoterapia/métodos , Linfócitos T/imunologiaRESUMO
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.
Assuntos
Doença de Hodgkin/patologia , Medição de Risco , Rituximab/uso terapêutico , Adulto , Idoso , Feminino , Histiócitos/patologia , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Linfócitos/patologia , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão/métodos , Rituximab/administração & dosagem , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The basilic/brachial (BBV), internal jugular (IJV), and subclavian veins (SCV) are commonly used as central venous catheter (CVC) sites. A BBV approach [peripherally inserted central catheter (PICC)] is increasingly used for short- to intermediate-term CVCs for acute leukemias undergoing cytotoxic intensive regimens. In this retrospective study, the catheterization of the BBV, IJV, and SCV in patients with previously untreated acute leukemia was assessed. The primary outcome was the composite incidence of catheter-related symptomatic deep-vein thrombosis (sDVT) and bloodstream infection (BSI) from catheterization up to 30 days later. In a 10-year period, 336 CVC were inserted in the BBV (n = 115), IJV (n = 111), and SCV (n = 110) in 336 patients suffering from AML (n = 201) and ALL (n = 135) and undergoing induction chemotherapy. The primary outcome events were 8, 20, and 27 in the BBV, SCV and IJV cohorts (2.6, 6.9, and 9.6 per 1000 catheter-days, respectively; p = 0.002). The primary outcome risk was significantly higher in the IJV-cohort than in the BBV-cohort (HR, 3.6; 95% CI, 1.6 to 7.9; p = 0.001) and in the SCV-cohort than in the BBV-cohort (HR, 2.6; 95% CI, 1.2 to 5.9; p = 0.02). PICC was a valid CVC for the induction chemotherapy of acute leukemia for the lowest risk of sDVT and BSI.