Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

被引：592

作者：

Sehn, Laurie H. ^{[1
,2
]}

Herrera, Alex F. ^{[3
]}

Flowers, Christopher R. ^{[4
]}

Kamdar, Manali K. ^{[5
]}

McMillan, Andrew ^{[6
]}

Hertzberg, Mark ^{[7
,8
]}

Assouline, Sarit ^{[9
]}

Kim, Tae Min ^{[10
]}

Kim, Won Seog ^{[11
]}

Ozcan, Muhit ^{[12
]}

Hirata, Jamie ^{[13
]}

Penuel, Elicia ^{[13
]}

Paulson, Joseph N. ^{[13
]}

Cheng, Ji ^{[14
]}

Ku, Grace ^{[13
]}

Matasar, Matthew J. ^{[15
]}

机构：

[1] BC Canc Ctr Lymphoid Canc, 600 West 10th Ave, Vancouver, BC V5Z 4E6, Canada

[2] Univ British Columbia, Vancouver, BC, Canada

[3] City Hope Natl Med Ctr, Duarte, CA USA

[4] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[5] Univ Colorado, Aurora, CO USA

[6] Nottingham Univ Hosp, Nottingham, England

[7] Prince Wales Hosp, Sydney, NSW, Australia

[8] Univ NSW, Sydney, NSW, Australia

[9] Jewish Gen Hosp, Montreal, PQ, Canada

[10] Seoul Natl Univ Hosp, Seoul, South Korea

[11] Samsung Med Ctr, Seoul, South Korea

[12] Ankara Univ, Ankara, Turkey

[13] Genentech Inc, San Francisco, CA 94080 USA

[14] F Hoffmann La Roche & Cie AG, Mississauga, ON, Canada

[15] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2020年 / 38卷 / 02期

关键词：

ANTIBODY-DRUG CONJUGATE; NON-HODGKIN-LYMPHOMA; PLUS RITUXIMAB; EXPRESSION; LEUKEMIA; BINDING;

D O I：

10.1200/JCO.19.00172

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE Patients with transplantation-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) fare poorly, with limited treatment options. The antibody-drug conjugate polatuzumab vedotin targets CD79b, a B-cell receptor component. METHODS Safety and efficacy of polatuzumab vedotin with bendamustine and obinutuzumab (pola-BG) was evaluated in a single-arm cohort. Polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) was compared with bendamustine and rituximab (BR) in a randomly assigned cohort of patients with transplantation-ineligible R/R DLBCL (primary end point: independent review committee [IRC] assessed complete response [CR] rate at the end of treatment). Duration of response, progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods. RESULTS Pola-BG and pola-BR had a tolerable safety profile. The phase Ib/II pola-BG cohort (n = 27) had a CR rate of 29.6% and a median OS of 10.8 months (median follow-up, 27.0 months). In the randomly assigned cohort (n = 80; 40 per arm), pola-BR patients had a significantly higher IRC-assessed CR rate (40.0% v 17.5%; P = .026) and longer IRC-assessed PFS (median, 9.5 v 3.7 months; hazard ratio [HR], 0.36, 95% CI, 0.21 to 0.63; P < .001) and OS (median, 12.4 v 4.7 months; HR, 0.42; 95% CI, 0.24 to 0.75; P = .002; median follow-up, 22.3 months). Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% v 33.3%), anemia (28.2% v 17.9%), and thrombocytopenia (41% v 23.1%), but similar grade 3-4 infections (23.1% v 20.5%), versus the BR group. Peripheral neuropathy associated with polatuzumab vedotin (43.6% of patients) was grade 1-2 and resolved in most patients. CONCLUSION Polatuzumab vedotin combined with BR resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with BR in patients with transplantation-ineligible R/R DLBCL. (C) 2019 by American Society of Clinical Oncology

引用

页码：155 / +

页数：22

共 22 条

[1]

[Anonymous], NCCN GUID DIFF LARG

[2]

[Anonymous], 2017, BLOOD S1

[3] New approach to classifying non-hodgkin's lymphomas: Clinical features of the major histologic subtypes [J].

Armitage, JO ;

Weisenburger, DD .

JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (08) :2780-2795

[4]

BAI R, 1990, J BIOL CHEM, V265, P17141

[5] Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification [J].

Cheson, Bruce D. ;

Fisher, Richard I. ;

Barrington, Sally F. ;

Cavalli, Franco ;

Schwartz, Lawrence H. ;

Zucca, Emanuele ;

Lister, T. Andrew .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :3059-+

[6] CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. [J].

Coiffier, B ;

Lepage, E ;

Brière, J ;

Herbrecht, R ;

Tilly, H ;

Bouabdallah, R ;

Morel, P ;

Van den Neste, E ;

Salles, G ;

Gaulard, P ;

Reyes, F ;

Gisselbrecht, C .

NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (04) :235-242

[7] Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study [J].

Crump, Michael ;

Neelapu, Sattva S. ;

Farooq, Umar ;

Van den Neste, Eric ;

Kuruvilla, John ;

Westin, Jason ;

Link, Brian K. ;

Hay, Annette ;

Cerhan, James R. ;

Zhu, Liting ;

Boussetta, Sami ;

Feng, Lei ;

Maurer, Matthew J. ;

Navale, Lynn ;

Wiezorek, Jeff ;

Go, William Y. ;

Gisselbrecht, Christian .

BLOOD, 2017, 130 (16) :1800-1808

[8] Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma [J].

Dornan, David ;

Bennett, Fiona ;

Chen, Yvonne ;

Dennis, Mark ;

Eaton, Dan ;

Elkins, Kristi ;

French, Dorothy ;

Go, Mary Ann T. ;

Jack, Andrew ;

Junutula, Jagath R. ;

Koeppen, Hartmut ;

Lau, Jeffrey ;

McBride, Jacqueline ;

Rawstron, Andy ;

Shi, Xiaoyan ;

Yu, Nancy ;

Yu, Shang-Fan ;

Yue, Peng ;

Zheng, Bing ;

Ebens, Allen ;

Polson, Andrew G. .

BLOOD, 2009, 114 (13) :2721-2729

[9] Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era [J].

Gisselbrecht, Christian ;

Glass, Bertram ;

Mounier, Nicolas ;

Gill, Devinder Singh ;

Linch, David C. ;

Trneny, Marek ;

Bosly, Andre ;

Ketterer, Nicolas ;

Shpilberg, Ofer ;

Hagberg, Hans ;

Ma, David ;

Briere, Josette ;

Moskowitz, Craig H. ;

Schmitz, Norbert .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (27) :4184-4190

[10] Preclinical Activity of the Type II CD20 Antibody GA101 (Obinutuzumab) Compared with Rituximab and Ofatumumab In Vitro and in Xenograft Models [J].

Herter, Sylvia ;

Herting, Frank ;

Mundigl, Olaf ;

Waldhauer, Inja ;

Weinzierl, Tina ;

Fauti, Tanja ;

Muth, Gunter ;

Ziegler-Landesberger, Doris ;

Van Puijenbroek, Erwin ;

Lang, Sabine ;

Minh Ngoc Duong ;

Reslan, Lina ;

Gerdes, Christian A. ;

Friess, Thomas ;

Baer, Ute ;

Burtscher, Helmut ;

Weidner, Michael ;

Dumontet, Charles ;

Umana, Pablo ;

Niederfellner, Gerhard ;

Bacac, Marina ;

Klein, Christian .

MOLECULAR CANCER THERAPEUTICS, 2013, 12 (10) :2031-2042

← 1 2 3 →