Contributions
Abstract: PB2445
Type: Publication Only
Background
Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation affecting 30% to 70% of patients. It is the leading cause of late non-relapse mortality, contributes to morbidity and impairs quality of life of transplant patients. Corticosteroids are standard first-line therapy for cGVHD, but around 50% of patients do not respond adequately. Evidence on the comparative efficacy of second-line treatments is limited, partly because, until the 2005 National Institutes of Health (NIH) Consensus Conference (revised in 2014) no uniform criteria for the diagnosis of cGVHD and response were available.
Aims
To systematically review the available clinical trials to investigate the efficacy of systemic treatments on response in patients with steroid-refractory (SR) cGVHD.
Methods
A systematic review of English-language publications was performed using Scopus and Cochrane Central Register of Controlled Trials databases. Literature was searched from 2005 to October 2017. The review was limited to phase 2 to 4 clinical trials that used the NIH Consensus Criteria for diagnosing cGVHD and determining response, and included >25 patients per study arm. Data on response were extracted from the included trials. Overall response rate [ORR] was defined as: (number of patients with complete response [CR] + number of patients with partial response [PR]) / total number of patients treated.
Results
Four phase 2, single arm trials were included. These investigated the efficacy of ibrutinib (n=1), interleukin-2 (IL-2; n=1), imatinib (n=1), and rituximab (n=1). Most trials failed to report response at a fixed time point and reported best response at any time during the follow-up, thus CR and PR data presented below are maximum response rates. At median follow-up of 13.9 months, CR with ibrutinib was 21% and PR was 45% (ORR: 67%; 28/42 patients); 71% (20/28 patients) and 48% (12/25 patients) responders showed a sustained response of ≥20 and ≥32 weeks, respectively. With ibrutinib, 56% of patients with ≥2 involved organs showed a response in ≥2 organs, and 42% of patients with ≥3 involved organs showed a response in ≥3 organs. During 1 year follow-up, CR with rituximab was 22% and PR was 65% (ORR: 87%; 32/37 patients); 21 patients maintained their response for 1 year. Response rates with rituximab were higher in the musculoskeletal system (ORR: 100%), skin (ORR: 77%) and oral cavity (ORR: 71%) than those in the liver (ORR: 44%), eyes (ORR: 43%), gut (ORR: 33%), and lungs (ORR: 9%). Patients treated with IL-2 or imatinib had no CR. By week 12, 61% of patients (20/33 patients) treated with IL-2 had PR; response sites included skin (PR: 27%), joint/fascia (PR: 17%), lung (PR: 15%), liver (PR: 13%), and gastrointestinal tract (PR: 10%). During 6 months, PR with imatinib was 51% (20/39 patients); the best response rates were observed in the gut (PR: 50%), lungs (PR: 35%) and skin (PR: 32%). The definitions of SR cGVHD varied in the included clinical trials.
Conclusion
Findings suggest that patients with SR cGVHD treated with ibrutinib and rituximab can reach CR. However, none of the included clinical trials reported comparative data demonstrating superior efficacy in response for one particular agent over others. Heterogeneity in the definition of SR cGVHD and follow-up time did not allow direct comparison of results. Further controlled clinical trials with larger cohorts are needed.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Chronic graft-versus-host, Clinical outcome, Stem cell transplant, Systematic review
Abstract: PB2445
Type: Publication Only
Background
Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation affecting 30% to 70% of patients. It is the leading cause of late non-relapse mortality, contributes to morbidity and impairs quality of life of transplant patients. Corticosteroids are standard first-line therapy for cGVHD, but around 50% of patients do not respond adequately. Evidence on the comparative efficacy of second-line treatments is limited, partly because, until the 2005 National Institutes of Health (NIH) Consensus Conference (revised in 2014) no uniform criteria for the diagnosis of cGVHD and response were available.
Aims
To systematically review the available clinical trials to investigate the efficacy of systemic treatments on response in patients with steroid-refractory (SR) cGVHD.
Methods
A systematic review of English-language publications was performed using Scopus and Cochrane Central Register of Controlled Trials databases. Literature was searched from 2005 to October 2017. The review was limited to phase 2 to 4 clinical trials that used the NIH Consensus Criteria for diagnosing cGVHD and determining response, and included >25 patients per study arm. Data on response were extracted from the included trials. Overall response rate [ORR] was defined as: (number of patients with complete response [CR] + number of patients with partial response [PR]) / total number of patients treated.
Results
Four phase 2, single arm trials were included. These investigated the efficacy of ibrutinib (n=1), interleukin-2 (IL-2; n=1), imatinib (n=1), and rituximab (n=1). Most trials failed to report response at a fixed time point and reported best response at any time during the follow-up, thus CR and PR data presented below are maximum response rates. At median follow-up of 13.9 months, CR with ibrutinib was 21% and PR was 45% (ORR: 67%; 28/42 patients); 71% (20/28 patients) and 48% (12/25 patients) responders showed a sustained response of ≥20 and ≥32 weeks, respectively. With ibrutinib, 56% of patients with ≥2 involved organs showed a response in ≥2 organs, and 42% of patients with ≥3 involved organs showed a response in ≥3 organs. During 1 year follow-up, CR with rituximab was 22% and PR was 65% (ORR: 87%; 32/37 patients); 21 patients maintained their response for 1 year. Response rates with rituximab were higher in the musculoskeletal system (ORR: 100%), skin (ORR: 77%) and oral cavity (ORR: 71%) than those in the liver (ORR: 44%), eyes (ORR: 43%), gut (ORR: 33%), and lungs (ORR: 9%). Patients treated with IL-2 or imatinib had no CR. By week 12, 61% of patients (20/33 patients) treated with IL-2 had PR; response sites included skin (PR: 27%), joint/fascia (PR: 17%), lung (PR: 15%), liver (PR: 13%), and gastrointestinal tract (PR: 10%). During 6 months, PR with imatinib was 51% (20/39 patients); the best response rates were observed in the gut (PR: 50%), lungs (PR: 35%) and skin (PR: 32%). The definitions of SR cGVHD varied in the included clinical trials.
Conclusion
Findings suggest that patients with SR cGVHD treated with ibrutinib and rituximab can reach CR. However, none of the included clinical trials reported comparative data demonstrating superior efficacy in response for one particular agent over others. Heterogeneity in the definition of SR cGVHD and follow-up time did not allow direct comparison of results. Further controlled clinical trials with larger cohorts are needed.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Chronic graft-versus-host, Clinical outcome, Stem cell transplant, Systematic review