2016研究t细胞淋巴瘤课件

ALCANZA: Brentuximab Vedotin vs Methotrexate or Bexarotene in Patients With CD30-Positive Cutaneous T-Cell Lymphoma,New Findings in Hematology: Independent Conference Coverage of ASH 2016*; December 3-6, 2016; San Diego, California,*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.,This activity is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, and Seattle Genetics.,ALCANZA: Background,CTCL: heterogeneous group of TCLs with skin involvement1,2 Generally chronic with quality of life affected by debilitating pruritus and skin infections MF and pcALCL most common CD30+ CTCLs Current treatments for advanced disease not associated with consistent long-term responses3 Brentuximab vedotin: anti-CD30 mAb conjugated to monomethyl auristatin E4 Phase II studies found clinical activity in MF and pcALCL with reasonable safety profile4,5 Current ALCANZA trial evaluated efficacy and safety of brentuximab vedotin vs methotrexate or bexarotene in treatment-experienced pts with CD30+ CTCL6,1. Swerdlow SH, et al. Blood. 2016;127:2375-2390. 2. Rosen ST, et al. Hematology Am Soc Hematol Educ Program. 2006:323-330. 3. Jawed SI, et al. J Am Acad Dermatol. 2014;70:223.e1-17. 4. Duvic M, et al. J Clin Oncol. 2015;33:3759-3765. 5. Kim YH, et al. J Clin Oncol. 2015;33:3750-3758. 6. Kim YH, et al. ASH 2016. Abstract 182.,Slide credit: ,ALCANZA: Study Design,Open-label, randomized, phase III trial1 Primary endpoint: ORR4 by independent review Secondary endpoints Rate of CR PFS Symptom burden/pt-reported outcomes (quality-of-life measurement with Skindex-292),Slide credit: ,1. Kim YH, et al. ASH 2016. Abstract 182. 2. Chren MM, et al. Arch Dermatol. 1997;133:1433-1440.,*Diagnosed by central review of 1 biopsy (2 for MF), where 10% neoplastic cells/lymphoid infiltrate CD30+.,ALCANZA: Baseline Characteristics of Intent-to-Treat Population,Slide credit: ,Kim YH, et al. ASH 2016. Abstract 182.,*1 pt per arm excluded because of incomplete staging data. Stage IVB MF only in brentuximab arm (n = 7).,ALCANZA: ORR4, PFS, CR, and Change in Symptom Burden,PFS significantly improved for subgroups defined by pt characteristics (baseline ECOG PS of 0, sex, age 65 yrs, geographical region), disease characteristics (MF and pcALCL, skin involvement, baseline skin tumor score), and treatment (bexarotene and methotrexate),Kim YH, et al. ASH 2016. Abstract 182.,*Adjusted P value from weighted Holms procedure. HR: 0.270 (95% CI: 0.169-0.430).,Slide credit: ,ALCANZA: ORR4 by Disease Type and Stage,Slide credit: ,Kim YH, et al. ASH 2016. Abstract 182.,ALCANZA: ORR4 by Key Demographic Subgroups,Slide credit: ,Kim YH, et al. ASH 2016. Abstract 182.,ALCANZA: ORR4 by Key Disease and Treatment Subgroups,Slide credit: ,Kim YH, et al. ASH 2016. Abstract 182.,ALCANZA: Safety and Tolerability,4 deaths in brentuximab arm during study period 3 deemed unrelated to study drug (1 each: lymphoma progression, pulmonary embolism, sepsis) 1 pt with T3bN0M1 pcALCL died due to multiple organ dysfunction related to tumor necrosis at visceral disease sites attributed to brentuximab vedotin,*Brentuximab arm: peripheral neuropathy, n = 9; skin hypersensitivity, n = 3; E coli infection, n = 1; impetigo, n = 1; pulmonary embolism, n = 1; urticaria, n = 1; vertigo, n = 1. Methotrexate or bexarotene arm: maculopapular rash, n = 1; asthenia, n = 1; hematuria, n = 1; hypernatremia, n = 1; neutropenia, n = 1; periorbital infection, n = 1; somnolence, n = 1.,Slide credit: ,Kim YH, et al. ASH 2016. Abstract 182.,ALCANZA: Common Treatment-Emergent AEs,*Drug exposure: median 12 cycles (36 wks) of brentuximab vedotin vs 17 wks of bexarotene or 9 wks of methotrexate. 30% of pts receiving bexarotene experienced elevated triglycerides.,Slide credit: ,Kim YH, et al. ASH 2016. Abstract 182.,ALCANZA: Conclusions,Brentuximab vedotin showed significantly longer ORR4 vs methotrexate/bexarotene in pts with CD30+ MF and pcALCL (56.3% vs 12.5%, respectively; P .0001) Significantly higher rates observed with brentuximab vedotin vs methotrexate/bexarotene for ORR, CR, PFS, and life quality symptom burden Brentuximab vedotin safety profile consistent with previous reports Investigators suggest that brentuximab vedotin may be valuable in managing pts with CD30+ CTCL requiring systemic treatment,Slide credit: ,Kim YH, et al. ASH 2016. Abstract 182.,/oncology,Go Online for More CCO C