Reinduction of PD1-inhibitor therapy: first experience in eight patients with metastatic melanoma

被引:46
作者
Blasig, Hanna [1 ]
Bender, Carolin [2 ]
Hassel, Jessica C. [2 ]
Eigentler, Thomas K. [3 ]
Sachse, Michael M. [4 ]
Hiernickel, Julia [1 ]
Koop, Anika [1 ]
Satzger, Imke [1 ]
Gutzmer, Ralf [1 ]
机构
[1] Hannover Med Sch, Skin Canc Ctr Hannover, Dept Dermatol & Allergy, Carl Neuberg Str 1, D-30625 Hannover, Germany
[2] Univ Hosp Heidelberg, Dept Dermatol, Heidelberg, Germany
[3] Univ Hosp Tuebingen, Dept Dermatol, Tubingen, Germany
[4] Hosp Bremerhaven Reinkenheide, Dept Dermatol Phlebol & Allergol, Bremerhaven, Germany
关键词
checkpoint-inhibitor; melanoma; PD1-inhibitor; retreatment; UNTREATED MELANOMA; BRAF-INHIBITOR; NIVOLUMAB; IPILIMUMAB;
D O I
10.1097/CMR.0000000000000341
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Significant progress has been made in the treatment of metastatic melanoma during the last years. Approval of immune-checkpoint inhibitors and targeted therapies has been achieved recently. The sequencing of these therapies is an important issue. Here, we report our experience with the treatment and retreatment with PD1-inhibitors (PD1i) in eight patients. The patients (two female and seven male with a median age of 70 years, all melanoma stage IV, M1c) underwent a first treatment period with PD1i for a median of 5.5 months. Three (37.5%) patients had a stable disease as best response, two (25%) showed progression, two (25%) showed partial response, and one (12.5%) achieved complete remission. PD1i was discontinued due to disease progression in seven patients and due to side effects (pancreatitis) in one patient. Patients were subsequently treated with ipilimumab (n=2), or chemotherapy (n=4), or no other medical treatment (n=2). All eight patients were subsequently retreated with PD1i for a median of 2.5 months. One (12.5%) developed a partial response, whereas in three patients (37.5%) the disease was stabilized. PD1i have shown a high and durable response rate in the first-line treatment of metastatic melanoma. Our study suggests PD1i retreatment as a reasonable option for selected patients. Further investigations are needed to verify the value of PD1i re-exposure and to identify subgroups of patients who can benefit.
引用
收藏
页码:321 / 325
页数:5
相关论文
共 10 条
[1]
Final Version of 2009 AJCC Melanoma Staging and Classification [J].
Balch, Charles M. ;
Gershenwald, Jeffrey E. ;
Soong, Seng-jaw ;
Thompson, John F. ;
Atkins, Michael B. ;
Byrd, David R. ;
Buzaid, Antonio C. ;
Cochran, Alistair J. ;
Coit, Daniel G. ;
Ding, Shouluan ;
Eggermont, Alexander M. ;
Flaherty, Keith T. ;
Gimotty, Phyllis A. ;
Kirkwood, John M. ;
McMasters, Kelly M. ;
Mihm, Martin C., Jr. ;
Morton, Donald L. ;
Ross, Merrick I. ;
Sober, Arthur J. ;
Sondak, Vernon K. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (36) :6199-6206
[2]
Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial. [J].
Hodi, F. Stephen ;
Sznol, Mario ;
Kluger, Harriet M. ;
McDermott, David F. ;
Carvajal, Richard D. ;
Lawrence, Donald P. ;
Topalian, Suzanne Louise ;
Atkins, Michael B. ;
Powderly, John D. ;
Sharfman, William Howard ;
Puzanov, Igor ;
Smith, David C. ;
Leming, Philip D. ;
Lipson, Evan J. ;
Taube, Janis M. ;
Anders, Robert ;
Horak, Christine E. ;
Kollia, Georgia ;
Gupta, Ashok Kumar ;
Sosman, Jeffrey Alan .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (15)
[3]
Hodi FS, 2015, COMMUNICATION
[4]
Hodi FS, 2010, J CLIN ONCOL, V28, P8509
[5]
Intermittent BRAF-inhibitor therapy is a feasible option: report of a patient with metastatic melanoma [J].
Koop, A. ;
Satzger, I. ;
Alter, M. ;
Kapp, A. ;
Hauschild, A. ;
Gutzmer, R. .
BRITISH JOURNAL OF DERMATOLOGY, 2014, 170 (01) :220-222
[6]
Larkin J, 2015, NEW ENGL J MED, V373, P23, DOI [10.1056/NEJMoa1504030, 10.1056/NEJMc1509660]
[7]
Durable Cancer Regression Off-Treatment and Effective Reinduction Therapy with an Anti-PD-1 Antibody [J].
Lipson, Evan J. ;
Sharfman, William H. ;
Drake, Charles G. ;
Wollner, Ira ;
Taube, Janis M. ;
Anders, Robert A. ;
Xu, Haiying ;
Yao, Sheng ;
Pons, Alice ;
Chen, Lieping ;
Pardoll, Drew M. ;
Brahmer, Julie R. ;
Topalian, Suzanne L. .
CLINICAL CANCER RESEARCH, 2013, 19 (02) :462-468
[8]
Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma [J].
Postow, Michael A. ;
Chesney, Jason ;
Pavlick, Anna C. ;
Robert, Caroline ;
Grossmann, Kenneth ;
McDermott, David ;
Linette, Gerald P. ;
Meyer, Nicolas ;
Giguere, Jeffrey K. ;
Agarwala, Sanjiv S. ;
Shaheen, Montaser ;
Ernstoff, Marc S. ;
Minor, David ;
Salama, April K. ;
Taylor, Matthew ;
Ott, Patrick A. ;
Rollin, Linda M. ;
Horak, Christine ;
Gagnier, Paul ;
Wolchok, Jedd D. ;
Hodi, F. Stephen .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (21) :2006-2017
[9]
Successful rechallenge in two patients with BRAF-V600-mutant melanoma who experienced previous progression during treatment with a selective BRAF inhibitor [J].
Seghers, Amelie Clementine ;
Wilgenhof, Sofie ;
Lebbe, Celeste ;
Neyns, Bart .
MELANOMA RESEARCH, 2012, 22 (06) :466-472
[10]
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial [J].
Weber, Jeffrey S. ;
D'Angelo, Sandra P. ;
Minor, David ;
Hodi, F. Stephen ;
Gutzmer, Ralf ;
Neyns, Bart ;
Hoeller, Christoph ;
Khushalani, Nikhil I. ;
Miller, Wilson H., Jr. ;
Lao, Christopher D. ;
Linette, Gerald P. ;
Thomas, Luc ;
Lorigan, Paul ;
Grossmann, Kenneth F. ;
Hassel, Jessica C. ;
Maio, Michele ;
Sznol, Mario ;
Ascierto, Paolo A. ;
Mohr, Peter ;
Chmielowski, Bartosz ;
Bryce, Alan ;
Svane, Inge M. ;
Grob, Jean-Jacques ;
Krackhardt, Angela M. ;
Horak, Christine ;
Lambert, Alexandre ;
Yang, Arvin S. ;
Larkin, James .
LANCET ONCOLOGY, 2015, 16 (04) :375-384