RESUMO
BACKGROUND: Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. METHODS: This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1-3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1-7), and prednisone (40 mg/m2 orally on days 1-14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503). FINDINGS: Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24-42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65-0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45-0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6-96·1) for BrECADD and 90·9% (88·7-93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7-99·5) and 98·2% (97·2-99·3), respectively. INTERPRETATION: BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma. FUNDING: Takeda Oncology.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin/administração & dosagem , Brentuximab Vedotin/efeitos adversos , Brentuximab Vedotin/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/administração & dosagem , Dacarbazina/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Dexametasona/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Doença de Hodgkin/mortalidade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Peripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV-induced neuropathy (BV-CN) is a mild distal sensory axonal polyneuropathy. Severe BV-induced inflammatory neuropathies (BV-IN) have been described. BV-IN contribute to lymphoma-associated morbidity but might be immunotherapy-responsive. Our primary objective was to evaluate the rate of BV-IN. Our secondary objectives were to determine risk factors and warning signs. METHODS: We conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV-induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV-IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV-CN. RESULTS: Among 83 patients, 41 (49%) developed neuropathy: 35 BV-CN and 6 BV-IN. Thus, the rate of BV-IN was 7.2%. Compared to patients with BV-CN, no predisposing factor was identified. However, patients with BV-IN more frequently presented muscle weakness (67% vs. 5.7%, p < 0.05), gait disorders (83% vs. 20%, p < 0.05), or acute or subacute onset (67% vs. 14%, p < 0.05). BV-IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%, p < 0.05). Four patients were treated with immunotherapy. CONCLUSIONS: Brentuximab vedotin-induced neuropathy is an overlooked complication. Based on four easily identifiable "red flags", we provide an algorithm to help non-neurologist physicians that care for BV-treated patients to detect BV-IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy.
Assuntos
Antineoplásicos Imunológicos , Brentuximab Vedotin , Doenças do Sistema Nervoso Periférico , Humanos , Masculino , Brentuximab Vedotin/efeitos adversos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adulto , Linfoma/tratamento farmacológicoRESUMO
Hodgkin lymphoma is characterized by a high cure rate in the modern era of medicine regardless of stage, but patients suffer from a high risk of comorbidity associated with the administered therapy. The main aim of this review article is to assess and analyze the various comorbidities associated with Hodgkin lymphoma and address the survivorship of patients, including fertility, secondary cancers due to cardiovascular toxicity, and quality of life. Furthermore, this review explores the optimal strategy for detecting relapse. The treatment paradigm of Hodgkin lymphoma has shifted, with a paradigm shift toward achieving a high cure rate and low toxicity as a standard of care in this patient population. Checkpoint inhibitors, especially nivolumab, in combination with chemotherapy are increasingly being studied in the first line of therapy. However, their long-term toxicity remains to be assessed in longer follow-up. In conclusion, Hodgkin lymphoma survivors, regardless of their treatment, should be followed up individually by a multidisciplinary survivorship team in order to detect and properly treat the long-term side effects of therapy.
Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Brentuximab Vedotin/efeitos adversos , Qualidade de Vida , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Brentuximab vedotin (BV) has obtained approval for the therapeutic management of classical Hodgkin lymphoma as well as systemic anaplastic large cell lymphoma. Given the inherent constraints of conventional clinical trials, the correlation between BV and cardiac adverse events (AEs) remains enigmatic. The objective of this investigation is to comprehensively assess cardiac AEs attributed to BV by employing advanced data mining techniques, utilizing the FDA Adverse Event Reporting System (FAERS). The indices for the assessment of disproportionality encompass the reporting odds ratio (ROR), the proportional reporting ratio, the information component, and the empirical Bayesian geometric mean. Employing these sophisticated metrics, we gauged the extent of disproportionate occurrences. The dataset was sourced from the FAERS from the first quarter of 2012 to first quarter of 2023, facilitating a comprehensive analysis of the potential correlation between BV and cardiac AEs. This scrutiny encompassed a comparative analysis of both cardiac and non-cardiac AEs. A total of 495 cases of BV's cardiac AEs were discerned, with the identification of 31 preferred terms (PTs). Among these, 8 PTs emerged as conspicuous signals of cardiac AEs, notably encompassing ventricular hypokinesia (ROR 7.59), tachyarrhythmia (ROR 7.06), sinus tachycardia (ROR 6.18), cardiopulmonary failure (ROR 4.44), pericardial effusion (ROR 4.32), acute coronary syndrome (ROR 4.02), cardiomyopathy (ROR 3.30), and tachycardia (ROR 2.76). The manifestation of severe outcomes demonstrates a discernible correlation with the cardiac AEs (P < 0.001). Our investigation furnishes invaluable insights for healthcare practitioners to proactively mitigate the incidence of BV-associated cardiac AEs.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Brentuximab Vedotin , United States Food and Drug Administration , Humanos , Brentuximab Vedotin/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Estados Unidos/epidemiologia , Bases de Dados Factuais , Cardiotoxicidade , Masculino , Feminino , Antineoplásicos Imunológicos/efeitos adversos , Pessoa de Meia-Idade , Teorema de Bayes , Mineração de DadosRESUMO
BACKGROUND: Brentuximab vedotin (BV) was approved as a therapy for patients with CD30-positive lymphoma in China in 2020 based on the results of multiple clinical trails. Few Chinese real-world data of its use are yet available. Herein, we present the application situation of BV in patients with lymphoma among different hospitals in Henan province in China under real-world conditions. METHODS: This was a multicenter and retrospective study in 104 patients with lymphoma who received BV for the first time between August 2020 and September 2022 across eight centers in Henan province. Data on the clinical use, effectiveness and adverse events (AEs) of BV were extracted from patient medical records. Short-term effectiveness was assessed based on objective response rate (ORR), complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier method. Safety was also evaluated in our study. RESULTS: 104 lymphoma patients were enrolled in our study, who had completed a median of two cycles (range,1-8) of BV-based treatment. A total of 72.1% of patients were relapsed/refractory (R/R) lymphoma, and only 27.9% were previously untreated lymphoma who received BV in frontline treatment settings. Among them who received effectiveness evaluation, the ORR achieved 64.5% (CR 25.8%, PR 38.7%). After a median follow-up of 11 months, the 6-month PFS rate and OS rate achieved 77.2% and 90.1% respectively, and the 12-month PFS rate and OS rate achieved 77.2% and 79.9% respectively. In general, BV-based treatment was well-tolerated, with 38.5% incidence of grade ≥3 AEs. The most commonly reported AEs were hematologic disorders, especially neutropenia, with the incidence reaching 50.0%. CONCLUSIONS: BV-based regimens could be a promising therapeutic option with remarkable effectiveness and moderate toxicity in treating Chinese lymphoma patients with CD30 expression.
Assuntos
Doença de Hodgkin , Imunoconjugados , Linfoma , Humanos , Brentuximab Vedotin/uso terapêutico , Brentuximab Vedotin/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Imunoconjugados/efeitos adversos , Linfoma/tratamento farmacológico , Linfoma/induzido quimicamenteRESUMO
The JSH Practical Guidelines for Hematological Malignancies, 2018 expanded edition, newly adopted brentuximab vedotin, doxorubicin, vinblastine, dacarbazine(A+AVD)protocol as a standard treatment for advanced-stage classical Hodgkin lymphoma(CHL). Therefore, this retrospective analysis compared 15 patients who received A+AVD therapy with 21 patients who received doxorubicin, bleomycin, vinblastine, dacarbazine(ABVD)therapy. All patients were newly diagnosed with CHL and received induction therapy between April 2015 and June 2022 in our hospital. All except 1 patient of the A+AVD group had advanced-stage CHL. The median age was 63(23-85)years. The estimated 2-year overall survival of the A+AVD group was better than that of the ABVD group which included 6 patients with clinical stage â ¢ or higher CHL (100% vs 66.7%, p=0.047). In contrast, there was no significant difference in the complete response rate(53.8% vs 100%, p=0.109)between the 2 groups. The overall response rate after first-line treatment(69.2% vs 100%, p=0.255), and the estimated 2-year progression-free survival(70.1% vs 66.7%, p=0.321)between the A+AVD and the ABVD groups were similar.
Assuntos
Doença de Hodgkin , Humanos , Pessoa de Meia-Idade , Doença de Hodgkin/tratamento farmacológico , Brentuximab Vedotin/efeitos adversos , Vimblastina/uso terapêutico , Vimblastina/efeitos adversos , Dacarbazina/uso terapêutico , Doxorrubicina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Retrospectivos , Bleomicina/uso terapêutico , Estadiamento de NeoplasiasRESUMO
ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) with or without radiation has been the standard treatment for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim positron emission tomography response. Thirty-four patients with nonbulky stage I-II HL were enrolled. Risk was early favorable in 53% and unfavorable in 47%. The overall and complete response rates (CRRs) were 100% and 97%, respectively, with a 5-year progression-free survival (PFS) of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%), and fatigue (56%). There were no cases of grade-4 neutropenia or neutropenic fever, and no patient received granulocyte-colony stimulating factor. Most cases of PN were grade 1, and no patient experienced grade ≥3 PN. BV-AD produced a high CRR and durable PFS with most patients requiring 4 cycles of therapy. Compared with BV-AVD, the toxicity profile appeared improved, with predominantly grade 1 reversible PN and no case of grade 4 neutropenia or neutropenic fever. This regimen warrants further study in HL and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269).
Assuntos
Doença de Hodgkin , Neutropenia , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Brentuximab Vedotin/efeitos adversos , Dacarbazina/efeitos adversos , Doxorrubicina/efeitos adversos , Doença de Hodgkin/patologia , Neutropenia/induzido quimicamente , Vimblastina/efeitos adversosRESUMO
BACKGROUND: In adults with advanced-stage Hodgkin's lymphoma, the CD30-directed antibody-drug conjugate brentuximab vedotin combined with multiagent chemotherapy has been shown to have greater efficacy, but also more toxic effects, than chemotherapy alone. The efficacy of this targeted therapy approach in children and adolescents with Hodgkin's lymphoma is unclear. METHODS: We conducted an open-label, multicenter, randomized, phase 3 trial involving patients 2 to 21 years of age with previously untreated Hodgkin's lymphoma of stage IIB with bulk tumor or stage IIIB, IVA, or IVB. Patients were assigned to receive five 21-day cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (brentuximab vedotin group) or the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (standard-care group). Slow-responding lesions, defined by a score of 4 or 5 (on a 5-point scale, with scores of 1 to 3 indicating rapid-responding lesions), were identified on centrally reviewed positron-emission tomography-computed tomography after two cycles. Involved-site radiation therapy was administered after the fifth cycle of therapy to slow-responding lesions and to large mediastinal adenopathy that was present at diagnosis. The primary end point was event-free survival, defined as the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died. Safety and overall survival were assessed. RESULTS: Of 600 patients who were enrolled across 153 institutions, 587 were eligible. At a median follow-up of 42.1 months (range, 0.1 to 80.9), the 3-year event-free survival was 92.1% (95% confidence interval [CI], 88.4 to 94.7) in the brentuximab vedotin group, as compared with 82.5% (95% CI, 77.4 to 86.5) in the standard-care group (hazard ratio for event or death, 0.41; 95% CI, 0.25 to 0.67; P<0.001). The percentage of patients who received involved-site radiation therapy did not differ substantially between the brentuximab vedotin group and the standard-care group (53.4% and 56.8%, respectively). Toxic effects were similar in the two groups. Overall survival at 3 years was 99.3% (95% CI, 97.3 to 99.8) in the brentuximab vedotin group and 98.5% (95% CI, 96.0 to 99.4) in the standard-care group. CONCLUSIONS: The addition of brentuximab vedotin to standard chemotherapy resulted in superior efficacy, with a 59% lower risk of an event or death, and no increase in the incidence of toxic effects at 3 years. (Funded by the National Institutes of Health and others; AHOD1331 ClinicalTrials.gov number, NCT02166463.).
Assuntos
Antineoplásicos Imunológicos , Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotin , Doença de Hodgkin , Adolescente , Adulto , Criança , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/efeitos adversos , Brentuximab Vedotin/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/efeitos adversosAssuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doença de Hodgkin , Imunoconjugados , Linfoma Anaplásico de Células Grandes , Linfoma , Humanos , Brentuximab Vedotin/efeitos adversos , Linfoma/complicações , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Imunoconjugados/efeitos adversosRESUMO
BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available. METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed. RESULTS: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up. CONCLUSIONS: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).
Assuntos
Antineoplásicos Imunológicos , Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotin , Doença de Hodgkin , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Brentuximab Vedotin/administração & dosagem , Brentuximab Vedotin/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversosAssuntos
Alopecia em Áreas , Micose Fungoide , Neoplasias Cutâneas , Alopecia em Áreas/induzido quimicamente , Alopecia em Áreas/diagnóstico , Alopecia em Áreas/tratamento farmacológico , Brentuximab Vedotin/efeitos adversos , Humanos , Micose Fungoide/diagnóstico , Micose Fungoide/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológicoAssuntos
Doença de Hodgkin , Imunoconjugados , Linfoma Anaplásico de Células Grandes , Linfoma , Pancreatite , Brentuximab Vedotin/efeitos adversos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Humanos , Imunoconjugados/efeitos adversos , Antígeno Ki-1 , Linfoma/complicações , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Pancreatite/induzido quimicamente , Pancreatite/diagnóstico , FarmacovigilânciaRESUMO
INTRODUCTION: Brentuximab vedotin (BV) showed high overall remission rates in refractory/relapsed classical Hodgkin's lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Although the efficacy of BV has been reported in clinical trials, its efficacy as a frontline therapy in real world for patients with CD30 positive subtypes of non-Hodgkin's lymphoma (NHL) such as peripheral T-cell lymphoma with T-follicular helper cell (TFH) phenotype (PTCL, TFH), anaplastic large-cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL) in China has not been well documented. METHODS: Analysis of a real-world, observational, retrospective case series in patients suffering from AITL, sALCL and peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) and other types of PTCL treated with BV in frontline treatment was conducted. The patients were given treatment from May 2020 till June 28, 2021. All patients were pathologically diagnosed to have PTCL before treatment and expressed CD30. Patients received BV (1.8 mg/kg) combined with CEP (cyclophosphamide, epirubicin, prednisone acetate every 3 weeks). The primary endpoint was objective response rates (ORR), and secondary endpoints were duration of response and incidence of adverse events (AEs). Exploratory endpoints such as progression-free survival (PFS) are discussed even though after such a short period. RESULTS: Nineteen patients completed ≥ 1 cycles of BV-CEP treatment (16 cases completed ≥ 4 cycles, 3 cases only completed 1 cycle). Among them, the ORR reached 89.5% [CR 52.7%; partial response (PR) 36.8%]. In the ALCL group, CR reached 100% with the median duration of response of up to 8 months, while in the AITL group, the ORR was 75% and 2 patients had disease progression after treatment with BV + CEP. We also observed that BV-CEP may extend the PFS compared to traditional chemotherapy such as the CHOEP regimen (BV-CEP: not evaluable, CHOEP: 6.5 months), although the median follow-up was only 6.7 months. Adverse events (AEs), including incidence and severity of febrile neutropenia (26% patients in the BV-CEP group and 30% in the CHOEP group), were similar between groups. There was no incidence of AEs leading to treatment withdrawal or death under BV-CEP treatment. CONCLUSION: BV is a promising treatment in patients with ALCL, AITL and PTCL-TFH in frontline treatment settings.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células T Periférico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin/efeitos adversos , Ciclofosfamida/efeitos adversos , Epirubicina/efeitos adversos , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Prednisona/efeitos adversos , Estudos RetrospectivosAssuntos
Infecções por Vírus Epstein-Barr , Doença de Hodgkin , Imunoconjugados , Linfoma Difuso de Grandes Células B , Brentuximab Vedotin/efeitos adversos , Infecções por Vírus Epstein-Barr/induzido quimicamente , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4 , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologiaRESUMO
New therapies are needed for patients with relapsed/refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) who do not benefit from or are ineligible for stem cell transplant and chimeric antigen receptor therapy. The CD30-targeted, antibody-drug conjugate brentuximab vedotin (BV) and the immunomodulator lenalidomide (Len) have demonstrated promising activity as single agents in this population. We report the results of a phase 1/dose expansion trial evaluating the combination of BV/Len in rel/ref DLBCL. Thirty-seven patients received BV every 21 days, with Len administered continuously for a maximum of 16 cycles. The maximum tolerated dose of the combination was 1.2 mg/kg BV with 20 mg/d Len. BV/Len was well tolerated with a toxicity profile consistent with their use as single agents. Most patients required granulocyte colony-stimulating factor support because of neutropenia. The overall response rate was 57% (95% CI, 39.6-72.5), complete response rate, 35% (95% CI, 20.7-52.6); median duration of response, 13.1 months; median progression-free survival, 10.2 months (95% CI, 5.5-13.7); and median overall survival, 14.3 months (95% CI, 10.2-35.6). Response rates were highest in patients with CD30+ DLBCL (73%), but they did not differ according to cell of origin (P = .96). NK cell expansion and phenotypic changes in CD8+ T-cell subsets in nonresponders were identified by mass cytometry. BV/Len represents a potential treatment option for patients with rel/ref DLBCL. This combination is being further explored in a phase 3 study (registered on https://clinicaltrials.org as NCT04404283). This trial was registered on https://clinicaltrials.gov as NCT02086604.
Assuntos
Brentuximab Vedotin , Lenalidomida , Linfoma Difuso de Grandes Células B , Brentuximab Vedotin/efeitos adversos , Humanos , Imunoconjugados/efeitos adversos , Lenalidomida/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do TratamentoRESUMO
Positron emission tomography (PET)-adapted chemotherapy and radiotherapy approaches are currently used for the initial treatment of early-stage Hodgkin lymphoma (HL) with progression-free survival and overall survival exceeding 85% and 95%, respectively. However, despite general agreement on the prognostic value of interim PET in HL, frontline treatment approaches vary among institutions with respect to how pretreatment clinical risk factors determine treatment selection, the definition of PET negativity, which chemotherapy regimen to initiate and how many cycles to administer, and when to incorporate radiation. Furthermore, as recent trials have confirmed improved efficacy and manageable toxicity when brentuximab and checkpoint inhibitors are combined with frontline regimens such as doxorubicin, vinblastine, and dacarbazine in advanced-stage HL, these agents are now under evaluation as frontline therapy in early-stage HL. A number of issues will affect the use of these agents in early-stage HL, including the costs, early and late toxicities with these agents, patient population (favorable or unfavorable risk groups), how to incorporate them (concurrently or sequentially), and whether they can ultimately replace cytotoxic therapy with similar efficacy and fewer late effects. Future treatment paradigms for early-stage HL may change significantly once randomized studies are completed incorporating these agents into frontline therapy. Ideally, frontline use of brentuximab and checkpoint inhibitors in early-stage HL will result in improved outcomes compared with current PET-adapted approaches with decreased risks of late toxicities that continue to afflict long-term survivors of HL.
Assuntos
Doença de Hodgkin/terapia , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/efeitos adversos , Brentuximab Vedotin/uso terapêutico , Gerenciamento Clínico , Detecção Precoce de Câncer , Feminino , Doença de Hodgkin/diagnóstico , Humanos , Tomografia por Emissão de Pósitrons , Adulto JovemRESUMO
BACKGROUND: Relapsed/refractory (R/R) classical HL (cHL) and systemic anaplastic large-cell lymphoma (sALCL) treatment options are limited in China. There is a need for new therapies. RESEARCH DESIGN AND METHODS: This single-arm, open-label, multicenter, Phase II study assessed efficacy, safety, and pharmacokinetics of single-agent brentuximab vedotin in Chinese patients with R/R cHL or sALCL. Patients received brentuximab vedotin 1.8 mg/kg by intravenous infusion on Day 1 of 3-week cycles (maximum 16 cycles). RESULTS: Patients (N = 39) received a median of 10 cycles (range: 2-16) of brentuximab vedotin. The objective response rate was 69% (95% CI: 52-83%), with 27 patients achieving objective responses (complete response: n = 11 [28%]; partial response: n = 16 [41%]). Median duration of response, progression-free survival and overall survival were 12.1 months, 13.5 months (95% CI: 6.8 months-not estimable) and not reached after a median follow-up of 16.6 months. Brentuximab vedotin was well tolerated with no on-study deaths. AEs were generally manageable and reversible. No new safety signals were identified. Pharmacokinetics were consistent with those previously described in Western populations. CONCLUSION: Brentuximab vedotin had a positive benefit-risk profile for Chinese patients with R/R cHL or sALCL, confirming it as a potential treatment option. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT02939014.