Pancreatitis in patients treated with brentuximab vedotin: a previously unrecognized serious adverse event.
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ABSTRACT:
SUBMITTER: Gandhi MD
PROVIDER: S-EPMC4007615 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
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Pancreatitis in patients treated with brentuximab vedotin: a previously unrecognized serious adverse event.
Gandhi Mitul D MD Evens Andrew M AM Fenske Timothy S TS Hamlin Paul P Coiffier Bertrand B Engert Andreas A Moskowitz Alison J AJ Ghosh Nilanjan N Petrich Adam M AM Lomasney Jon J Chadburn Amy A Wood Gary S GS Salva Katrin K Nardone Beatrice B Trifilio Steven M SM Raisch Dennis W DW West Dennis P DP Gordon Leo I LI Winter Jane N JN
Blood 20140501 18
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Project description:Brentuximab vedotin (SGN-35; Adcetris®) is an anti-CD30 antibody conjugated via a protease-cleavable linker to the potent anti-microtubule agent monomethyl auristatin E (MMAE). Following binding to CD30, brentuximab vedotin is rapidly internalized and transported to lysosomes where MMAE is released and binds to tubulin, leading to cell cycle arrest and apoptosis. Several trials have shown durable antitumor activity with a manageable safety profile in patients with relapsed/refractory Hodgkin lymphoma, systemic anaplastic large cell lymphoma, or primary cutaneous CD30-positive lymphoproliferative disorders. Peripheral sensory neuropathy is a significant adverse event associated with brentuximab vedotin administration. Neuropathy symptoms are cumulative and dose-related. Multiple ongoing trials are currently evaluating brentuximab vedotin alone or in combination with other agents in relapsed/refractory patients, as well as patients with newly diagnosed disease.
| S-EPMC3499340 | biostudies-literature
Project description:Brentuximab vedotin (cAC10-vcMMAE; SGN 35; SGN-35) is an anticancer antibody-drug conjugate under development by Seattle Genetics Inc. and its licensee Millennium: The Takeda Oncology Company. It comprises the anti-CD30 monoclonal antibody cAC10 conjugated to the cytotoxic agent monomethyl auristatin E, a synthetic analog of the tubulin polymerization inhibitor dolastatin 10. It is under investigation for use in Hodgkin lymphoma and non-Hodgkin lymphoma (specifically anaplastic large cell lymphoma) in North America and Europe. This review discusses the key development milestones and therapeutic trials of this drug.
| S-EPMC3585690 | 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:BackgroundPatients with advanced urothelial carcinoma have poor overall survival after platinum-containing chemotherapy and programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor treatment.MethodsWe conducted a global, open-label, phase 3 trial of enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and had had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor. Patients were randomly assigned in a 1:1 ratio to receive enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight on days 1, 8, and 15 of a 28-day cycle) or investigator-chosen chemotherapy (standard docetaxel, paclitaxel, or vinflunine), administered on day 1 of a 21-day cycle. The primary end point was overall survival.ResultsA total of 608 patients underwent randomization; 301 were assigned to receive enfortumab vedotin and 307 to receive chemotherapy. As of July 15, 2020, a total of 301 deaths had occurred (134 in the enfortumab vedotin group and 167 in the chemotherapy group). At the prespecified interim analysis, the median follow-up was 11.1 months. Overall survival was longer in the enfortumab vedotin group than in the chemotherapy group (median overall survival, 12.88 vs. 8.97 months; hazard ratio for death, 0.70; 95% confidence interval [CI], 0.56 to 0.89; P = 0.001). Progression-free survival was also longer in the enfortumab vedotin group than in the chemotherapy group (median progression-free survival, 5.55 vs. 3.71 months; hazard ratio for progression or death, 0.62; 95% CI, 0.51 to 0.75; P<0.001). The incidence of treatment-related adverse events was similar in the two groups (93.9% in the enfortumab vedotin group and 91.8% in the chemotherapy group); the incidence of events of grade 3 or higher was also similar in the two groups (51.4% and 49.8%, respectively).ConclusionsEnfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based treatment and a PD-1 or PD-L1 inhibitor. (Funded by Astellas Pharma US and Seagen; EV-301 ClinicalTrials.gov number, NCT03474107.).
| S-EPMC8450892 | biostudies-literature
Project description: Not available
| S-EPMC6589112 | biostudies-literature
Project description:BackgroundAntibody-drug conjugates have recently been introduced as a treatment for advanced urothelial carcinoma. The EV-301 study demonstrated that enfortumab vedotin (EV) improved overall survival compared with conventional chemotherapy. To assess the cost-effectiveness of EV for the treatment of advanced urothelial carcinoma (UC) from a payer perspective in middle- and high-income countries.MethodsA decision analysis model was developed to assess the efficacy and economic viability of EV as a subsequent-line treatment following disease progression in patients with advanced urothelial carcinoma already treated with PD-1 or PD-L1 inhibitors. Clinical and utility values were obtained from the published literature and available databases. Cost data were obtained from payer perspectives in the United States, United Kingdom, and China. Quality-adjusted life-years (QALYs) were used to measure health outcomes, and incremental cost-effectiveness ratios (ICERs) used to evaluate cost-effectiveness in comparison to willingness-to-pay in the United States, United Kingdom, and China. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model.ResultsCompared with chemotherapy, EV increased the benefit by 0.16-0.17 QALYs, resulting in ICERs of $2,168,746.71, $2,164,494.38, and $1,775,576.56 per QALY in the United States, United Kingdom, and China, respectively. One-way sensitivity analysis indicated that the largest effect on outcome was the utility value for progression-free survival. Probabilistic sensitivity analysis demonstrated that the probability of EV being cost-effective was 0%.ConclusionsEV provides an additional health benefit over chemotherapy for patients with advanced urothelial carcinoma but is not cost-effective from a payer perspective in the United States, United Kingdom, or China.
| S-EPMC8796084 | biostudies-literature
Project description:BackgroundBrentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856).MethodsTwenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment.ResultsThe objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year.Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment.DiscussionWith the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials.ConclusionsRetreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL.Trial registrationUnited States registry and results database ClinicalTrials.gov NCT00947856.
| S-EPMC3994656 | biostudies-literature
Project description:Brentuximab vedotin is a conjugate drug used mainly in Hodgkin lymphoma, systemic and primary cutaneous anaplastic large cell lymphomas, and CD30-expressing peripheral T-cell lymphoma. We report a unique case of acute pancreatitis associated with brentuximab vedotin in a 17-year-old male patient suffering from classical Hodgkin lymphoma. Diagnosed in 2020, the patient was classified to an intermediate therapeutic group and disease's grade was IIIAE. The patient was treated with brentuximab vedotin and bendamustine in the third line. Two weeks after the drug administration, the patient developed acute epigastric pain. Laboratory and radiological findings confirmed the clinical suspicion of acute pancreatitis that was managed with opioid pain medications, meropenem, parenteral nutrition, ondansetron and omeprazole. This is the first case report of brentuximab vedotin-associated acute pancreatitis in the pediatric patient reported in the literature to the best of our knowledge.
| S-EPMC9416696 | biostudies-literature
Project description:Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted accelerated approval in 2011 by the US Food and Drug Administration. Thereafter, many large-scale trials in various situations have been performed, which led to extensions of the original indication. The aim of this review was to describe the latest updates on clinical trials of BV and the in-practice guidance for the use of BV.
| S-EPMC5762734 | biostudies-literature
Project description:PurposeBrentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with classical Hodgkin lymphoma (HL), was introduced in this frontline trial to reduce prescribed radiation in children and adolescents with classical HL.MethodsOpen-label, single-arm, multicenter trial for patients (age ≤ 18 years) with stage IIB, IIIB, or IV classical HL was conducted. Brentuximab vedotin replaced each vincristine in the OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) regimen according to GPOH-HD2002 treatment group 3 (TG3); two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after two cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free (EFS) and overall survival (OS). The trials are registered at ClinicalTrials.gov (identifier: NCT01920932).ResultsOf the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3.4 years, the 3-year EFS was 97.4% (SE 2.3%) and the OS was 98.7% (SE 1.6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% of patients experienced grade 3 neuropathy.ConclusionThe integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes.
| S-EPMC8260923 | biostudies-literature