P1130: FRONTLINE BRENTUXIMAB VEDOTIN AND CHP (A+CHP) IN PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA WITH LESS THAN 10% CD30 EXPRESSION: INITIAL SAFETY AND EFFICACY RESULTS FROM THE PHASE 2 STUDY SGN35-032
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SUBMITTER: Iyer S
PROVIDER: S-EPMC10430937 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30+ peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.8+ to 66.0+ months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV+CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789.
| S-EPMC5946765 | biostudies-literature
Project description:Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas, the majority of which have high relapse rates 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; clinicaltrials.gov) demonstrated 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+ PTCL (ALK- anaplastic large cell lymphoma [ALCL] and non-ALCL) who were in complete response (CR) after frontline treatment with A+CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone. Median PFS follow-up was 47.57 months. The PFS hazard ratio was 0.36, equating to a 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, vs 55.66 months in patients who did not undergo SCT. PFS results favored the use of SCT in both ALK- ALCL and non-ALCL subgroups. These data support the consideration of consolidative SCT in patients with CD30+PTCL who achieve CR following treatment with A+CHP.
| S-EPMC9647727 | biostudies-literature
Project description:Intravenous brentuximab vedotin (ADCETRIS®) is a targeted antibody-drug conjugate (ADC) active against CD30-positive cancer cells such as those associated with classical Hodgkin lymphoma (HL). In noncomparative, phase 2 trials and in the real-world setting, salvage therapy with brentuximab vedotin resulted in high objective response (complete plus partial remission) rates in patients with relapsed or refractory CD30-positive HL, including as retreatment in patients who had an objective response to previous brentuximab vedotin therapy and subsequently relapsed. These beneficial outcomes were durable during long-term follow-up. As consolidation therapy after autologous haematopoietic stem cell transplant (ASCT) in the multinational, phase 3 AETHERA trial, brentuximab vedotin prolonged progression-free-survival (PFS) compared with placebo at a median follow-up of 30 months (primary analysis), with a 43% reduction in the risk of disease progression or death. The beneficial effects of brentuximab vedotin consolidation therapy were maintained during long-term follow-up. In the clinical trial and real-world setting, brentuximab vedotin had an acceptable tolerability and safety profile, with most adverse events manageable with dose reductions and/or delays [including peripheral sensory neuropathy (PSN) and neutropenia]. With a paucity of treatments available for many patients with relapsed or refractory HL, brentuximab vedotin represents an important option for the management of patients who have failed high-dose chemotherapy/ASCT or at least two prior chemotherapy regimens and as post-ASCT consolidation therapy in patients who are at increased risk/high-risk of relapse or progression after ASCT.
| S-EPMC7102329 | biostudies-literature
Project description:Monoclonal antibodies (mAb) have become an effective treatment strategy for hematologic malignancies. CD30 is a rational target for therapy due to its limited expression on normal tissues and the strong and uniform expression on malignant cells in classical Hodgkin's lymphoma (cHL) and anaplastic large-cell lymphoma (ALCL). Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, utilizes the targeting properties of mAb to deliver a cytotoxic agent inside the malignant cell. Brentuximab vedotin has significant clinical activity in patients with relapsed or refractory cHL and relapsed or refractory ALCL, and has the potential to represent a significant advance in modern oncology.
| S-EPMC3873074 | biostudies-other
Project description:BackgroundIn the randomised controlled trial ECHELON-2 (NCT01777152; January 2013), brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin and prednisone (CHP) demonstrated improved efficacy compared with CHOP (CHP and vincristine) in frontline CD30+ peripheral T-cell lymphoma (PTCL), an aggressive cancer with poor survival. In ECHELON-2, 70% of patients had systemic anaplastic large cell lymphoma (sALCL), a subtype of PTCL. Of sALCL patients who progressed from BV+CHP and CHOP, 36% (n = 17) and 56% (n = 36) received subsequent BV-containing therapy, respectively. As BV re-treatment was not funded in England at the time, our objective was to estimate adjusted efficacy and cost-effectiveness by excluding BV re-treatment from BV+CHP.MethodsTo remove the effects of BV re-treatment, the inverse probability of censoring weights (IPCW) and two-stage estimator (TSE) approaches, with and without re-censoring, were applied to overall survival (OS) in the BV+CHP arm of the ECHELON-2 sALCL population. Cost-effectiveness was determined in a three-state partitioned survival (PartSA) model from the perspective of the National Health Service (NHS) in England.ResultsThe unadjusted hazard ratio (HR) for death in patients with sALCL with BV+CHP versus CHOP was 0.54 (95% CI 0.34, 0.87; p = 0.011). The model base case used TSE analysis without re-censoring, which provided an adjusted HR for death of 0.55 (95% CI 0.33, 0.86; p = 0.014). Incremental cost-effectiveness ratios (ICERs) including and excluding re-treatment with BV were £29,760/QALY and £27,761/QALY, respectively.ConclusionTSE without re-censoring provided the most clinically plausible estimate of survival whilst retaining sufficient information for OS extrapolation. After adjustment for BV re-treatment, BV+CHP remains an efficacious and cost-effective treatment in frontline sALCL compared with CHOP.
| S-EPMC9596633 | biostudies-literature
Project description:The expression of CD30 receptors is one of the defining characteristics of the malignant Reed-Sternberg cells of Hodgkin lymphoma (HL). CD30 is rarely expressed by normal cells and is rapidly internalized, making it an ideal therapeutic target for monoclonal antibodies and for antibody-drug conjugates. Brentuximab vedotin is the first antibody-drug conjugate to be approved by regulatory agencies for the treatment of patients with relapsed HL, with a single-agent response rate of 75%. In this review article, we discuss the current and ongoing development of brentuximab vedotin in patients with relapsed and newly diagnosed HL.
| S-EPMC5042201 | biostudies-literature
Project description:BackgroundThe safety and efficacy of brentuximab vedotin (BV), an antibody-drug conjugate directed to the CD30 antigen, has been assessed in several trials in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell non-Hodgkin lymphoma (NHL). The objective of this research was to examine the relationship between CD30 expression level and clinical response to BV.Patients and methodsWe analyzed response in patients treated with BV monotherapy in 5 prospective clinical studies in relapsed or refractory PTCL, CTCL, or B-cell NHL. CD30 expression was assessed by immunohistochemistry (IHC) using the Ber H2 antibody for 275 patients.ResultsAcross all 5 studies, 140 (50.9%) patients had tumors with CD30 expression <10%, including 60 (21.8%) with undetectable CD30 by IHC. No significant differences were observed for any study in overall response rates between patients with CD30 expression ≥10% or <10%. Median duration of response was also similar in the CD30 ≥10% and <10% groups for all studies.ConclusionsIn this analysis of studies across a range of CD30-expressing lymphomas, CD30 expression alone, as measured by standard IHC, does not predict clinical benefit from BV, making the determination of a threshold level of expression uncertain.
| S-EPMC9526494 | biostudies-literature
Project description:Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Brentuximab vedotin is an effective treatment of relapsed CD30-expressing Classical Hodgkin and systemic anaplastic large cell lymphomas. Herein, we demonstrated that PEL cell lines and primary tumors express CD30 and thus may serve as potential targets for brentuximab vedotin therapy. In vitro treatment with brentuximab vedotin decreased cell proliferation, induced cell cycle arrest, and triggered apoptosis of PEL cell lines. Furthermore, in vivo brentuximab vedotin promoted tumor regression and prolonged survival of mice bearing previously reported UM-PEL-1 tumors as well as UM-PEL-3 tumors derived from a newly established and characterized Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-positive PEL cell line. Overall, our results demonstrate for the first time that brentuximab vedotin may serve as an effective therapy for PEL and provide strong preclinical indications for evaluation of brentuximab vedotin in clinical studies of PEL patients.
| S-EPMC3744990 | biostudies-literature
Project description:IntroductionBrentuximab vedotin (SGN-35), an anti-cluster of differentiation (CD)-30 antibody conjugated to the anti-tubulin agent monomethyl auristatin E, has demonstrated promising efficacy and tolerability in relapsed and heavily treated Hodgkin lymphoma (HL). In this study, we report the Asian experience with brentuximab vedotin in patients with relapsed or refractory CD30-positive (CD30+) HL.MethodsThis is an observational, multicenter, retrospective study. Between October 2011 and June 2013, a total of 22 patients were treated with brentuximab vedotin under a named patient program in Asia. Patients received a 30 min infusion of brentuximab vedotin at a dose of 1.8 mg/kg of body weight every 3 weeks.ResultsFour patients (18.2%) showed a complete response, and the overall response rate was 72.7%. The median duration of response was 4.4 months (range 1.0-17.4). The median progression-free survival was 5.7 months, and the median overall survival has not yet been reached. The 1-year expected survival rate was 67.2%. The most common grade 3/4 adverse events were neutropenia (n=7; 31.8%). No patients experienced grade 3/4 sensory neuropathy.ConclusionsThese results confirm that brentuximab vedotin as a single agent is also effective and well tolerated when used in Asian patients with relapsed and refractory CD30+ HL.
| S-EPMC4196794 | biostudies-literature
Project description: Not available
| S-EPMC6290106 | biostudies-literature