治疗晚期或转移性尿路上皮癌的抗体偶联药物:enfortumab vedotin

enfortumab vedotin为一种抗体偶联药物,可与nectin-4结合释放出小分子细胞毒药物单甲基奥瑞他汀E。单甲基奥瑞他汀E具有抗有丝分裂的作用,能作用于微管蛋白抑制肿瘤生长。enfortumab vedotin可用于治疗晚期或转移性尿路上皮癌。常见不良反应有疲劳、外周神经病变、食欲下降、皮疹等。     

Poikilodermatous mycosis fungoides with CD30‐positive large cell transformation successfully treated by brentuximab vedotin

We present a patient with a 33‐year history of poikilodermatous mycosis fungoides (MF) who subsequently developed CD30‐positive large cell transformation. After 6 years of conventional MF treatment, side effects of therapy and/or concomitant diseases prevented the previously applied treatment modalities. The CD30‐directed antibody‐cytotoxic drug conjugate (brentuximab vedotin) was introduced and followed by quick and excellent therapeutic response.     

Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma

The treatment of patients with relapsed and refractory Hodgkin lymphoma (HL), especially those who relapse after autologous stem cell transplantation, remains challenging. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities, and have a median survival of less than 3 years. Since no new drugs have been approved by the FDA for HL in more than three decades, there is a clear unmet medical need for drug development for this patient population. New treatment strategies that are based on targeting oncogenic signaling pathways are currently explored. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL.     

A Phase II Study of Telisotuzumab Vedotin in Patients With c–MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K,NCT03574753)

IntroductionLung-MAP S1400K was designed to evaluate the response to telisotuzumab vedotin, an antibody-drug conjugate targeting c-MET, in patients with c-MET–positive squamous cell carcinoma (SCC).Patients and MethodsPatients with previously treated SCC with c-MET–positive tumors (H score ≥ 150, Ventana SP44 assay) were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor-naive) and Cohort 2 (immune checkpoint inhibitor refractory). Telisotuzumab vedotin 2.7 mg/kg was administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included progression-free survival, overall survival, response within cohort, duration of response, and toxicities. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment.ResultsForty-nine patients (14% of screened patients) were assigned to S1400K, 28 patients enrolled (15 in Cohort 1 and 13 in Cohort 2), and 23 were eligible. S1400K closed on December 21, 2018 owing to lack of efficacy. Two responses (response rate of 9%; 95% confidence interval, 0%-20%) were reported in cohort 1 (1 complete and 1 unconfirmed partial response), whereas 10 patients had stable disease, with a disease control rate of 52%. The median overall and progression-free survival was 5.6 and 2.4 months, respectively. There were 3 grade 5 events (2 pneumonitis, in Cohort 2, and 1 bronchopulmonary hemorrhage, in Cohort 1).ConclusionTelisotuzumab vedotin failed to meet the pre-specified response needed to justify continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed in patients with SCC.     

A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B-cell lymphoma

Polatuzumab vedotin (pola) is a CD79b-targeted antibody-drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open-label, single-arm study of pola 1.8 mg/kg, bendamustine 90 mg/m², rituximab 375 mg/m² (pola + BR) Q3W for up to six cycles in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received ≥1 prior line of therapy and were ineligible for autologous stem cell transplantation (ASCT) or experienced treatment failure with prior ASCT. Primary endpoint was complete response rate (CRR) at the end of the treatment (EOT) by positron emission tomography–computed tomography (PET-CT) using modified Lugano Response Criteria. Secondary endpoints included efficacy, safety, and pharmacokinetics. Thirty-five patients (median age 71 [range 46-86] years) were enrolled. Twenty-three (66%) patients had refractory disease, and 23 (66%) had ≥2 prior lines of therapy. At a median follow-up of 5.4 (0.7-11.9) months, patients received a median of five treatment cycles. CRR was 34.3% (95% confidence interval [CI] 19.1-52.2) at EOT. Overall response rate was 42.9% at EOT, and median progression-free survival was 5.2 months (95% CI 3.6-not evaluable). Median overall survival was not reached. No fatal adverse events (AEs) were observed. Grade 3-4 AEs were mainly hematological: anemia (37%), neutropenia (31%), white blood cell count decreased (23%), thrombocytopenia/platelet count decreased/neutrophil count decreased (20% each), and febrile neutropenia (11%). Grade 1-2 peripheral neuropathy (PN; sensory and/or motor) was reported in 14% of patients; there were no ≥grade 3 PN events. This study (JapicCTI-184048) demonstrated the efficacy and safety of pola + BR in Japanese patients with R/R DLBCL who were ineligible for ASCT.     

Brentuximab vedotin in pretreated Hodgkin lymphoma patients: a systematic review and meta-analysis

ABSTRACT

Objectives: This meta-analysis evaluated the effect of single agent brentuximab vedotin (BV) in patients with relapsed/refractory Hodgkin lymphoma (HL).

Patients and methods: A systematic literature search was performed and included studies published from 1^st January 2012 to 1^st July 2015 investigating BV in patients with relapsed/refractory HL. Data was extracted and reviewed by two investigators then analyzed using the comprehensive meta-analysis version 3 software.

Results: 22 out of 4048 screened records met the eligibility criteria. These records included 903 patients. The median age of the cohort was 31 years (range: 26-45). 86% received ≥ 3 previous lines of systemic therapy. 529 (58.7%) and 232 (25.7%) underwent high dose chemotherapy and autologous and/or allogeneic stem transplantation prior of BV respectively. The overall response rate to BV was 62.7% (range: 30-100%). The complete response, partial response, stable disease and progressive disease rates were 31.8%, 35.1%, 19.5% and 11.7% respectively. The one year progression free survival and estimated one year overall survival were 47.6% and 79.5% respectively.

Conclusion: In this largest published pooled cohort, BV produces high responses with encouraging progression free and overall survival in relapsed/refractory HL patients. Our results enhance the role of BV in heavily pretreated HL patients.