Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study

被引：289

作者：

Ansell, Stephen M. ^{[1
]}

Minnema, Monique C. ^{[2
]}

Johnson, Peter ^{[3
]}

Timmerman, John M. ^{[4
]}

Armand, Philippe ^{[5
]}

Shipp, Margaret A. ^{[5
]}

Rodig, Scott J. ^{[5
,6
]}

Ligon, Azra H. ^{[6
]}

Roemer, Margaretha G. M. ^{[5
]}

Reddy, Nishitha ^{[7
]}

Cohen, Jonathon B. ^{[8
]}

Assouline, Sarit ^{[9
]}

Poon, Michelle ^{[10
]}

Sharma, Manish ^{[11
]}

Kato, Kazunobu ^{[11
]}

Samakoglu, Selda ^{[11
]}

Sumbul, Anne ^{[11
]}

Grigg, Andrew ^{[12
,13
]}

机构：

[1] Mayo Clin, 200 First St SW, Rochester, MN 55905 USA

[2] Univ Med Ctr Utrecht, Canc Ctr, Utrecht, Netherlands

[3] Univ Southampton, Southampton, Hants, England

[4] Univ Calif Los Angeles, Los Angeles, CA USA

[5] Dana Farber Canc Inst, Boston, MA 02115 USA

[6] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[7] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA

[8] Emory Univ, Atlanta, GA 30322 USA

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

[10] Natl Univ Canc Inst, Singapore, Singapore

[11] Bristol Myers Squibb, Princeton, NJ USA

[12] Austin Hosp, Melbourne, Vic, Australia

[13] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 37卷 / 06期

基金：

美国国家卫生研究院;

关键词：

DEATH LIGAND 1; HODGKIN LYMPHOMA; OPEN-LABEL; EXPRESSION; PD-L1; MULTICENTER; BLOCKADE; OUTCOMES;

D O I：

10.1200/JCO.18.00766

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PurposeTreatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL.MethodsIn this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1.ResultsAmong 121 treated patients, patients in the auto-HCT-failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT-ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT-failed cohort and 6 months in the auto-HCT-ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT-failed cohort and 1.4 and 5.8 months in the auto-HCT-ineligible cohort respectively. All three patients with complete remission3% of the auto-HCT-failed cohorthad durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification.ConclusionNivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.

引用

页码：481 / +

页数：13

共 29 条

[1] Programmed Death Ligand 1 Is Expressed by Non-Hodgkin Lymphomas and Inhibits the Activity of Tumor-Associated T Cells [J].

Andorsky, David J. ;

Yamada, Reiko E. ;

Said, Jonathan ;

Pinkus, Geraldine S. ;

Betting, David J. ;

Timmerman, John M. .

CLINICAL CANCER RESEARCH, 2011, 17 (13) :4232-4244

[2]

[Anonymous], 2014, WORLD CANC REP 2014

[3]

[Anonymous], NCCN CLIN PRACT GUID

[4] PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma [J].

Ansell, Stephen M. ;

Lesokhin, Alexander M. ;

Borrello, Ivan ;

Halwani, Ahmad ;

Scott, Emma C. ;

Gutierrez, Martin ;

Schuster, Stephen J. ;

Millenson, Michael M. ;

Cattry, Deepika ;

Freeman, Gordon J. ;

Rodig, Scott J. ;

Chapuy, Bjoern ;

Ligon, Azra H. ;

Zhu, Lili ;

Grosso, Joseph F. ;

Kim, Su Young ;

Timmerman, John M. ;

Shipp, Margaret A. ;

Armand, Philippe .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) :311-319

[5] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[6]

Bristol Myers Squibb, NIV OPD PRESCR INF

[7] PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies [J].

Chen, Benjamin J. ;

Chapuy, Bjoern ;

Jing Ouyang ;

Sun, Heather H. ;

Roemer, Margaretha G. M. ;

Xu, Mina L. ;

Yu, Hongbo ;

Fletcher, Christopher D. M. ;

Freeman, Gordon J. ;

Shipp, Margaret A. ;

Rodig, Scott J. .

CLINICAL CANCER RESEARCH, 2013, 19 (13) :3462-3473

[8] Revised response criteria for malignant lymphoma [J].

Cheson, Bruce D. ;

Pfistner, Beate ;

Juweid, Malik E. ;

Gascoyne, Randy D. ;

Specht, Lena ;

Horning, Sandra J. ;

Coiffier, Bertrand ;

Fisher, Richard I. ;

Hagenbeek, Anton ;

Zucca, Emanuele ;

Rosen, Steven T. ;

Stroobants, Sigrid ;

Lister, T. Andrew ;

Hoppe, Richard T. ;

Dreyling, Martin ;

Tobinai, Kensei ;

Vose, Julie M. ;

Connors, Joseph M. ;

Federico, Massimo ;

Diehl, Volker .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) :579-586

[9] 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

[10] Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation [J].

Freeman, GJ ;

Long, AJ ;

Iwai, Y ;

Bourque, K ;

Chernova, T ;

Nishimura, H ;

Fitz, LJ ;

Malenkovich, N ;

Okazaki, T ;

Byrne, MC ;

Horton, HF ;

Fouser, L ;

Carter, L ;

Ling, V ;

Bowman, MR ;

Carreno, BM ;

Collins, M ;

Wood, CR ;

Honjo, T .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :1027-1034

← 1 2 3 →