Long-term outcome and prospective validation of NIH response criteria in 39 patients receiving imatinib for steroid-refractory chronic GVHD

被引:79
作者
Olivieri, Attilio [1 ]
Cimminiello, Michele [2 ]
Corradini, Paolo [3 ]
Mordini, Nicola [4 ]
Fedele, Roberta [5 ,6 ]
Selleri, Carmine [7 ]
Onida, Francesco [8 ]
Patriarca, Francesca [9 ]
Pavone, Enzo [10 ]
Svegliati, Silvia [11 ]
Gabrielli, Armando [11 ]
Bresciani, Paola [12 ]
Nuccorini, Roberta [2 ]
Pascale, Sara [2 ]
Coluzzi, Sabrina [2 ]
Pane, Fabrizio [13 ]
Poloni, Antonella [1 ]
Olivieri, Jacopo [14 ]
Leoni, Pietro [1 ]
Bacigalupo, Andrea [15 ]
机构
[1] Univ Politecn Marche, Clin Ematol, Ancona, Italy
[2] Azienda Osped Reg San Carlo, UO Ematol Ctr Trapianto Cellule Staminali, Potenza, Italy
[3] Univ Milan, Fdn IRCCS Ist Nazl Tumori Milano, Milan, Italy
[4] Azienda Osped S Croce e Carle, Div Ematol, Cuneo, Italy
[5] Osped Bianchi Melacrino Morelli, Div Ematol, Reggio Di Calabria, Italy
[6] Osped Bianchi Melacrino Morelli, TMO, Reggio Di Calabria, Italy
[7] Univ Salerno, Dipartimento Med & Chirurgia, UOC Ematol, I-84100 Salerno, Italy
[8] Fdn IRCCS CaGranda, Div Ematol, Milan, Italy
[9] AOU Santa Maria della Misericordia, Clin Ematol, Udine, Italy
[10] Azienda Osped Card G Panico, Dipartimento Ematol, Ctr Trapianti Midollo Osseo, Tricase, Italy
[11] Univ Politecn Marche, Clin Med, Ancona, Italy
[12] Azienda Osped Univ Policlin, Modena, Italy
[13] Univ Naples Federico II, Div Ematol, Naples, Italy
[14] Univ Politecn Marche, Dipartimento Sci Clin & Mol, Ancona, Italy
[15] Azienda Osped Univ S Martino, Div Ematol 2, Genoa, Italy
关键词
VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; PDGF RECEPTOR; STIMULATORY AUTOANTIBODIES; THERAPEUTIC RESPONSE; LIMITED EFFICACY; CLINICAL-TRIALS; RISK-FACTORS; PHASE-II; MESYLATE;
D O I
10.1182/blood-2013-05-494278
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Forty adults aged 28 to 73 years were entered into a prospective trial of imatinib for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD). After 6 months, intention-to-treat (ITT) analysis of 39 patients who received the drug, regardless of the duration of treatment, revealed 14 partial responses (PR), 4 minor responses (MR) with relevant steroid sparing (46%) according to Couriel criteria, and 20 >= PR (51.3%), as per the National Institutes of Health (NIH) criteria and NIH severity score changes. The best responses were seen in the lungs, gut, and skin (35%, 50%, and 32%, respectively). After a median follow-up of 40 months, 28 patients were alive, with a 3-year overall survival (OS) and event-free survival of 72% and 46%, respectively. The 3-year OS was 94% for patients responding at 6 months and 58% for nonresponders according to NIH response, suggesting that these criteria represent a reliable tool for predicting OS after second-line treatment. Monitoring of anti-platelet-derived growth factor receptor (PDGF-R) antibodies showed a significant decrease in PDGF-R stimulatory activity in 7 responders, whereas it remained high in 4 nonresponders. This study confirms the efficacy of imatinib against SR-cGVHD and suggests that the response at 6 months significantly predicts long-term survival. This study is registered at https://eudract.ema.europa.eu/(EUDRACT number: 2009-012927-27).
引用
收藏
页码:4111 / 4118
页数:8
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