Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 402
Filtrar
1.
Chemotherapy ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35537403

RESUMO

Hepatosplenic T-cell lymphoma is a very difficult lymphoma to deal with, almost impossible to cure. "Tandem" consolidation therapy with auto- stem cell transplant and allo- stem cell transplant can induce a long-lasting response and potentially cure this disease.

2.
Tumori ; : 3008916221090327, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35441544

RESUMO

The follow-up of the pivotal trial and large case series reports of a proportion of patients, between 5% and 9%, with relapsed or refractory Hodgkin lymphoma failing autologous stem cell transplantation and treated with brentuximab vedotin, achieving and maintaining long lasting complete responses with no further treatment. Very long-term data on the outcomes of such patients are indeed underreported. Our institutional experience with patients meeting these characteristics and in continuous complete response for more than 5 years after brentuximab vedotin was reviewed. Five patients achieved a median duration of complete response of 7.4 (range 5.1-8.1) years, and none of them encountered disease relapse or received any subsequent consolidation, including allogeneic transplantation. A proportion of patients failing autologous transplantation and receiving subsequent brentuximab vedotin may reach a long-lasting complete response with no need of further treatment. These patients are therefore considered cured. The role of allogeneic transplantation in such patients is matter of debate.

3.
Blood Adv ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35470385

RESUMO

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas, the majority of which have a high relapse rate following standard therapy. Despite use of consolidative stem cell transplant (SCT) following frontline therapy, there remains no consensus on its utility. The double blind randomized phase 3 ECHELON-2 study (NCT01777152) demonstrated an improved progression-free survival (PFS) and overall survival with frontline brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP). Herein, we conducted an exploratory subgroups analysis of the impact of consolidative SCT on PFS in patients with previously untreated, CD30-positive PTCL (ALK-negative anaplastic large cell lymphoma [ALCL] and non-ALCL) who were in complete response (CR) at end of treatment with frontline A+CHP or CHOP. Median PFS follow-up was 47.57 months (95% CI, 41.89-48.16). The PFS hazard ratio was 0.36 (95% CI, 0.17-0.77), equating to an 64% reduction in the risk of a PFS event in patients who underwent SCT. The median PFS in patients who underwent SCT was not reached (95% CI, 49.81, NA), versus 55.66 months (95% CI, 19.88, NA) in patients who did not undergo SCT. PFS results favored the use of SCT in both ALK-negative ALCL and non-ALCL subgroups. These data support the consideration of consolidative SCT in patients with CD30-positive PTCL who achieve a CR following treatment with A+CHP.

4.
Cancers (Basel) ; 14(6)2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35326578

RESUMO

The preservation of fertility in cancer patients is a crucial aspect of modern reproductive medicine. Amenorrhea and infertility often occur after cancer therapy, worsening the quality of life. Cryopreservation of oocytes in young cancer patients is a therapeutic option for preserving fertility. A prospective study was conducted on 508 cancer patients who underwent oocyte cryopreservation to preserve fertility between 1996 and 2021 including the COVID-19 pandemic period. Patients underwent ovarian stimulation, followed by egg retrieval, and oocytes were cryopreserved by slow freezing or vitrification. Sixty-four thawing/warming cycles were performed. Survival, fertilization, pregnancy, and birth rate over the thawing/warming cycles were obtained. The data were compared with those from a group of 1042 nononcological patients who cryopreserved supernumerary oocytes. An average of 8.8 ± 6.9 oocytes were retrieved per cycle, and 6.1 ± 4.2 oocytes were cryopreserved. With their own stored oocytes, 44 patients returned to attempt pregnancy. From a total of 194 thawed/warmed oocytes, 157 survived (80%). In total, 100 embryos were transferred in 57 transfer/cycles, and 18 pregnancies were achieved. The pregnancy rate per transfer and pregnancy rate per patient were 31% and 41%, respectively. No statistically significant differences were observed between oncological patients and nononcological patients. A total of 15 babies were born from oncological patients. Children born showed normal growth and development. One minor malformation was detected.

5.
Hematol Oncol ; 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247223

RESUMO

The introduction of Bruton's tyrosine kinase (BTK) inhibitors transformed the management of patients with mantle cell lymphoma (MCL). Ibrutinib, the first-in-class BTK inhibitor is now approved in more than 80 countries and there are over 20 new BTK inhibitors in development. In addition, novel agents show potential clinical activity (alone and in combination) and are in the approval phase and/or being studied in ongoing clinical trials. How does the practicing clinician decide on the optimal therapeutic strategy for this highly heterogenous disease? In July 2020 a group of experts from Italy, convened a meeting to address and provide clarification on a series of outstanding issues in the treatment of MCL with the view of providing clinical guidance on its management. This expert opinion statement represents the panel's collective analysis, evaluation, and recommendations and is made up of a series of questions and answers (in the form of a review of the pertinent literature) designed to replicate those posed by practicing clinicians in Italy but which are applicable to clinical settings worldwide.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35239000

RESUMO

PURPOSE: One of the most critical issues in the management of Hodgkin lymphoma (HL) patients who resulted as primary relapsed or refractory is to obtain a minimal disease status before autologous stem cell transplantation (ASCT). Finding a salvage regimen able to induce this status without severe toxicity would represent a major achievement in this setting. METHODS: A single-center retrospective study was conducted to assess effectiveness and safety of BEGEV (bendamustine, gemcitabine, and vinorelbine) regimen as first salvage setting prior to ASCT in HL patients. RESULTS: Forty-three patients were treated in our institution between October 2017 and November 2020. Median age at BEGEV therapy was 35.0 years (range 17.2- 70.0), and the median time from frontline therapy to the first cycle of BEGEV was 79.5 days (range 4-2267). At the end of treatment, 31 patients achieved a complete response (CR), with an overall response rate of 76.7%. Forty-one patients harvested CD34+ cells and 35/43 (81.4%) patients underwent ASCT. With a median follow-up of 22 months, 4 CR patients had disease relapse, yielding an estimated disease-free survival of 73.9% at 34 months. The estimated 2-year progression-free survival was 66.7%. Response to first-line chemotherapy did not significantly influence prognosis. CONCLUSIONS: BEGEV regimen was well tolerated, and reversible haematological toxic effects were the most common adverse events. Real-life data on BEGEV regimen as first salvage setting showed a relevant rate of objective responses and a limited myelotoxicity with no impairment of a subsequent mobilization of peripheral blood stem cells.

8.
Hematol Oncol ; 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35168291

RESUMO

Rapid infusion (RI) of the rituximab biosimilar CT-P10 is currently only an approved treatment regimen for the treatment of rheumatoid arthritis. Although both CT-P10 and reference rituximab are known to be frequently administered using a RI regimen (≤90 min) in clinical practice, published data on the safety of RI of CT-P10 in patients with NHL and CLL are limited. Hence, this study collected real-world safety and effectiveness data on RI-CT-P10 from the medical records of 196 patients with NHL or CLL in 10 European centers, 6 months after the date of the first RI (index date); the infusion-related reaction (IRR) rate was compared to previously published data. Ten percent (95% confidence interval 6%-15%; n = 20/196) of patients experienced an infusion-related reaction (IRR) on day 1-2 post-index, which was not significantly different (p = 0.45) to the IRR rate for rituximab described in a previous meta-analysis (8.8%). During the observation period, 2% of patients experienced grade 3-5 IRRs and 85% (n = 166) experienced an adverse event (non-IRR). The most common reason for discontinuation of first-line CT-P10 was planned treatment completion (81%; n = 158). Complete response and partial response to CT-P10 was observed in 74% (n = 142/192) and 22% (n = 42/192) of patients, respectively. The results of this real-world study demonstrate that the safety and effectiveness profile of RI-CT-P10 is similar to RI of reference rituximab and therefore support the current use of RI-CT-P10 in patients with NHL and CLL.

9.
Blood Adv ; 6(7): 2035-2044, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35196377

RESUMO

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered.


Assuntos
Herpes Zoster , Linfoma de Zona Marginal Tipo Células B , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/efeitos adversos , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Pessoa de Meia-Idade , Rituximab/efeitos adversos , Adulto Jovem
10.
Hematol Oncol ; 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35212014

RESUMO

The pivotal role that ibrutinib plays in the management of Waldenström macroglobulinemia (WM) is undisputed but there are ongoing questions regarding its positioning in the therapeutic algorithm of WM as well as in some peculiar clinical situations. A panel of experts from Italy was convened to provide real world recommendations on the use of BTK inhibitors in lymphoproliferative diseases in general, and in patients with WM in particular. This position paper represents the panel's collective analysis, evaluation, and opinions and is made up of a series of questions frequently asked by practicing clinicians and answers based on currently available evidence.

11.
Sci Rep ; 12(1): 1753, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35110658

RESUMO

Immune checkpoint inhibitors (ICIs) show efficacy in the treatment of non-Hodgkin lymphomas (NHL). However, these agents are associated with a unique group of side effects called immune-related adverse events (irAEs). We conducted an observational retrospective/prospective study on patients with relapsed/refractory NHL treated with ICI to determine the incidence of irAEs assessing the type, severity, and timing of onset, outcome and relationship with study drugs of these events. Thirty-two patients underwent ICI as single agent (N = 20) or in combination (N = 12). Ten patients (31.3%) developed at least one irAE for a total of 17 irAEs. Median time to presentation of irAEs was 69 days (range 0-407) with a median resolution time of 16 days (range 0-98). Progression free survival at 24 months for patients who developed an irAE was 40% and 31.8% for who did not. Overall survival for the two groups did not differ (at 24 months 40.0% and 62.5% for patients without and with irAE, respectively), but the median for who developed an irAE was not reached. The incidence of irAEs was associated with better long-term survival in NHL treated with ICIs but patients' disease conditions need to be carefully evaluated to decide the optimal management.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Inibidores de Checkpoint Imunológico/efeitos adversos , Linfoma não Hodgkin , Adulto , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Doenças do Sistema Imunitário/etiologia , Imunoterapia/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
12.
Cancers (Basel) ; 14(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35158922

RESUMO

Follicular lymphoma (FL) is an indolent hematological disease, often responsive to the first line of treatment, but characterized by repeated relapses. The therapeutic algorithm for relapsed/refractory FL patients comprises phosphatidylinositol 3-kinase inhibitors. Idelalisib showed anticancer activity, while inducing a significant rate of toxicities. Since the evidence in the literature on its use in normal clinical practice is scarce, a retrospective multicenter study was conducted to evaluate effectiveness and tolerability in a real-life context. Seventy-two patients with a median age at diagnosis of 57.2 years-mostly with an advanced stage (88.9%) and relapsed to the most recent therapy (79.1%)-were enrolled. The median number of prior therapies was three (20.8% refractory to the last therapy before idelalisib). With a median number of 4 months of treatment, the overall response rate was 41.7% (20.8% complete responses). Median disease-free survival and overall survival were achieved at 8.4 months and at 4 years, respectively. Forty-four percent of patients experienced at least one drug-related toxicity: 6.9% hematological ones and 43% non-hematological. The study confirmed that idelalisib has anticancer effectiveness and an acceptable safety profile in relapsed/refractory FL with unfavorable prognostic characteristics, even in the context of normal clinical practice.

14.
Blood Adv ; 6(2): 590-599, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-34644372

RESUMO

KEYNOTE-204 (NCT02684292) demonstrated a progression-free survival advantage for pembrolizumab over brentuximab vedotin (BV) in patients who had relapsed or refractory classical Hodgkin lymphoma (R/R cHL) following, or who were ineligible for, autologous stem cell transplantation (ASCT). Health-related quality of life (HRQoL), measured by patient-reported outcomes (PROs) from KEYNOTE-204, are reported from patients who received ≥1 dose of study treatment and completed ≥1 PRO assessment. The EORTC QoL Questionnaire Core 30 (QLQ-C30) and EuroQoL EQ-5D were administered at baseline, every 6 weeks until week 24, and every 12 weeks thereafter. Prespecified end points included least squares mean (LSM) changes from baseline to week 24 and time to true deterioration (TTD; ≥10-point decline from baseline). Comparisons were evaluated using 2-sided P values uncontrolled for multiplicity. High compliance at baseline (>90%) and through week 24 (>80%) was demonstrated across treatment groups (PRO analysis set: pembrolizumab, n = 146; BV, n = 150). The EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) score improved from baseline to week 24 on pembrolizumab and worsened on BV and demonstrated significant LSM differences at 24 weeks (GHS/QoL: 8.60 [95% confidence interval, 3.89-13.31]; P = .0004). Significant improvements were observed in each QLQ-C30 domain except emotional and cognitive functioning. Compared with BV, pembrolizumab prolonged TTD for GHS/QoL (hazard ratio, 0.40 [95% CI, 0.22-0.74]; P = .003) and each QLQ-C30 domain except cognitive functioning. In conclusion, pembrolizumab demonstrated overall improvements in PROs of HRQoL measures over BV in the KEYNOTE-204 study. These data and previously reported efficacy results support pembrolizumab as the preferred treatment option for patients with R/R cHL who are ineligible for or experience relapse after ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin , Doença Crônica , Doença de Hodgkin/patologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Qualidade de Vida , Transplante Autólogo
15.
J Cancer Res Clin Oncol ; 148(1): 177-190, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34741682

RESUMO

PURPOSE: CD19 is a cell surface protein that is found on both healthy and malignant B cells. Accordingly, it has become an important target for novel treatments for non-Hodgkin lymphomas and B-cell leukaemia. Three anti-CD19 monoclonal antibodies with distinct mechanisms of action have been developed for the treatment of B-cell malignancies. METHODS: We reviewed the preclinical and clinical data on the development of the newly approved anti-CD19 monoclonal antibodies blinatumomab, tafasitamab and loncastuximab tesirine, and consider their place in the treatment of relapsed or refractory B-cell malignancies. RESULTS: Blinatumomab is a bispecific T-cell engager that binds to both CD19 on B cells and CD3 on T cells, facilitating antibody-dependent cytotoxicity. Blinatumomab significantly prolongs overall survival in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, although cytokine release syndrome and severe neurotoxicity may necessitate discontinuation. Tafasitamab, which has modified anti-CD19 Fab and Fc regions, has significantly enhanced affinity for both CD19 and effector cell receptors compared with unmodified anti-CD19. In L-MIND, tafasitamab plus lenalidomide provided an overall response rate (ORR) of 57.5% in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients non-transplant eligible. Loncastuximab tesirine is an antibody-drug conjugate that has been studied as monotherapy and in combination with ibrutinib in 3L + relapsed or refractory DLBCL. The ORR was 48.3% in a phase II trial of loncastuximab tesirine. The optimal place of anti-CD19 monoclonal antibodies in therapy has yet to be determined, but the prospect of improved outcomes for at least some patients with treatment-resistant B-cell malignancies appears likely, particularly in those with limited therapeutic options and poor prognosis.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD19/imunologia , Antineoplásicos/uso terapêutico , Benzodiazepinas/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adenina/análogos & derivados , Adenina/uso terapêutico , Linfócitos B/imunologia , Linfócitos B/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Piperidinas/uso terapêutico
16.
Acta Haematol ; 145(2): 207-209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34818217

RESUMO

Mycosis fungoides (MF) is a disease almost impossible to cure. In the context of heavily pretreated patients, the anti-programmed cell death protein 1 (anti-PD-1) pembrolizumab is a valid therapeutic option. The alteration of the PD-1-PD ligand 1 (PD-L1) axis is often present in MF, and this aspect explains the feasibility of this therapy. We report the case of a 60-year-old woman diagnosed with MF in 2003, Olsen stage IA (T1M0NXBO). Since the moment of the diagnosis, she received 10 lines of therapy, with a short duration of response after each one of them. In April 2020, our patient started pembrolizumab 2 mg/kg every 3 weeks, and she achieved a partial response after the 4th cycle, consistent with the modified severity assessment tool (mSWAT) 1, which she is still maintaining after 10 cycles. No grade ≥3 adverse events were recorded. We conclude that pembrolizumab can induce extremely rapid responses in MF, with very low toxicity.


Assuntos
Micose Fungoide , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Micose Fungoide/induzido quimicamente , Micose Fungoide/diagnóstico , Micose Fungoide/tratamento farmacológico , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico
17.
Hematol Oncol ; 40(1): 57-62, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34653277

RESUMO

BRAFV600E mutation is the pathogenic driver of hairy cell leukemia (HCL) found in the vast majority of cases both at onset and during recurrences. The identification of the mutated allele in blood and marrow correlates with the presence of neoplastic cells and can be considered a marker of active disease. Likewise, the absence of the mutation after treatment may indicate a state of deep response. The BRAFV600E burden was measured by droplet digital polymerase chain reaction (ddPCR) and expressed as fractional abundance in 35 HCL patients at different stages of disease (onset, relapse, complete response [CR] after treatment, long-term remission) in peripheral blood and/or bone marrow (when available). Mean values of fractional abundance for patients at diagnosis, relapse and response, respectively, were 12.26%, 16.52% and 0.02% in peripheral blood and 23.51%, 13.96% and 0.26% in bone marrow. Four patients out of 6 evaluated at response were molecularly negative for BRAFV600E in peripheral blood. Mean fractional abundance in peripheral blood tested in 14 patients with long lasting CR was 0.05%, and 10 patients were BRAFV600E negative. These preliminary results suggest that ddPCR permits to assess the active tumor burden in HCL at different disease phases and support the hypothesis that some patients in CR qualify for a molecular CR.


Assuntos
Biomarcadores Tumorais/genética , Leucemia de Células Pilosas/patologia , Mutação , Recidiva Local de Neoplasia/patologia , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Humanos , Leucemia de Células Pilosas/genética , Recidiva Local de Neoplasia/genética , Prognóstico
18.
Leukemia ; 36(1): 197-209, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34304248

RESUMO

Standard chemotherapies for diffuse large B-cell lymphoma (DLBCL), based on the induction of exogenous DNA damage and oxidative stress, are often less effective in the presence of increased MYC and BCL-2 levels, especially in the case of double hit (DH) lymphomas harboring rearrangements of the MYC and BCL-2 oncogenes, which enrich for a patient's population characterized by refractoriness to anthracycline-based chemotherapy. Here we hypothesized that adaptive mechanisms to MYC-induced replicative and oxidative stress, consisting in DNA damage response (DDR) activation and BCL-2 overexpression, could represent the biologic basis of the poor prognosis and chemoresistance observed in MYC/BCL-2-positive lymphoma. We first integrated targeted gene expression profiling (T-GEP), fluorescence in situ hybridization (FISH) analysis, and characterization of replicative and oxidative stress biomarkers in two independent DLBCL cohorts. The presence of oxidative DNA damage biomarkers identified a poor prognosis double expresser (DE)-DLBCL subset, characterized by relatively higher BCL-2 gene expression levels and enrichment for DH lymphomas. Based on these findings, we tested therapeutic strategies based on combined DDR and BCL-2 inhibition, confirming efficacy and synergistic interactions in in vitro and in vivo DH-DLBCL models. These data provide the rationale for precision-therapy strategies based on combined DDR and BCL-2 inhibition in DH or DE-DLBCL.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Enzimas Reparadoras do DNA/antagonistas & inibidores , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Ureia/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Ureia/farmacologia , Adulto Jovem
19.
Cancer ; 128(5): 1004-1014, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34726773

RESUMO

BACKGROUND: The clinical benefit of cusatuzumab, a CD70-directed monoclonal antibody with enhanced effector functions, was investigated in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL). METHODS: In this cohort expansion of the ARGX-110-1201 study, 27 patients with R/R CTCL received cusatuzumab at 1 (n = 11) or 5 mg/kg (n = 16) once every 3 weeks to investigate its safety, dose, and exploratory efficacy. The pharmacokinetics, immunogenicity, CD70 expression, and CD70/CD27 biology were also assessed. RESULTS: The most common adverse events included infusion-related reactions, pyrexia, and asthenia. Eighteen serious adverse events (grade 1-3) were reported in 11 patients; 1 of these (vasculitis) was considered drug-related. For 8 of the 11 patients receiving 1 mg/kg, anti-drug antibodies (ADAs) affected the minimal concentration, and this resulted in undetectable cusatuzumab concentrations at the end of treatment and, in some cases, a loss of response. This effect was greatly reduced in the patients receiving 5 mg/kg. The overall response rate was 23%; this included 1 complete response and 5 partial responses (PRs) in 26 of the 27 evaluable patients. In addition, 9 patients achieved stable disease. The mean duration on cusatuzumab was 5.2 months, and the median duration was 2.5 months. Patients with Sézary syndrome (SS) achieved a 60% PR rate with a dosage of 5 mg/kg and a 33% PR rate with a dosage of 1 mg/kg; this resulted in an overall response rate of 50% for patients with SS at both doses. CONCLUSIONS: Cusatuzumab was well tolerated, and antitumor activity was observed at both 1 and 5 mg/kg in highly pretreated patients with R/R CTCL. The observed dose-dependent effect on exposure supports the use of 5 mg/kg for future development.


Assuntos
Anticorpos Monoclonais , Antineoplásicos , Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/uso terapêutico , Ligante CD27 , Humanos , Linfoma Cutâneo de Células T/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
20.
Nat Med ; 28(2): 325-332, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34921238

RESUMO

Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8-20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8-78.3) and ORR 86.2% (95% confidence interval, 77.5-92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients.


Assuntos
Imunoterapia Adotiva , Linfoma Folicular , Receptores de Antígenos de Linfócitos T , Adulto , Antígenos CD19 , Humanos , Imunoterapia Adotiva/efeitos adversos , Linfoma Folicular/tratamento farmacológico , Projetos Piloto , Receptores de Antígenos de Linfócitos T/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...