All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional.
The gvhd Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the gvhd Hub cannot guarantee the accuracy of translated content. The gvhd and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The GvHD Hub is an independent medical education platform, sponsored by Medac and supported through grants from Sanofi and Therakos. The funders are allowed no direct influence on our content. The levels of sponsorship listed are reflective of the amount of funding given. View funders.
Now you can support HCPs in making informed decisions for their patients
Your contribution helps us continuously deliver expertly curated content to HCPs worldwide. You will also have the opportunity to make a content suggestion for consideration and receive updates on the impact contributions are making to our content.
Find out more
Create an account and access these new features:
Bookmark content to read later
Select your specific areas of interest
View gvhd content recommended for you
TCT Meeting 2019 | Primary data from a phase II trial of ixazomib for the treatment of refractory chronic graft-versus-host disease
On 21 February 2019 at the 2019 TCT Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR in Houston, Texas, USA, Joseph Pidala from H. Lee Moffitt Cancer Center, Tampa, FL, USA, presented results on behalf of colleagues of a single-arm, multicenter, phase II trial, conducted by the Chronic GvHD Consortium, evaluating the efficacy of ixazomib in advanced chronic graft-versus-host disease (cGvHD).
The primary objective of the study was treatment failure by six months (death, relapse, or new line of immune suppressive [IS] therapy). Secondary objectives included response at 3 and 6 months, overall survival (OS), non-relapse mortality (NRM), relapse, failure-free survival (FFS).
Patients and methods
- N = 50 heavily pretreated (≥ 3 prior lines of therapy) patients with cGvHD
- Median age: 58 years (range, 44–65)
- Follow-up: 1 year
- cGvHD organs involved: skin (84%), eye (76%), joint/fascia (74%), mouth (56%), lung (42%)
- Inclusion criteria: NIH cGvHD, failure at least one prior systemic (IS) therapy for cGvHD; age ≥ 18 years; adequate lab parameters (ANC ≥ 1,000, PLT ≥ 75,000, bilirubin ≤5 x ULN, AST/ALT ≤ 3 x ULN, CrCl ≥ 30 mL/min)
- Exclusion criteria: new systemic IS agent added for cGvHD within two weeks; uncontrolled infection; Hep B, C, HIV; strong inhibitors of CYP1A2, CYP3A, or strong CYP3A inducers; neuropathy (grade 2 with pain or grade ≥ 3); other malignancy within 2 years
- Ixazomib was administered at a dose of 4 mg per os weekly on days 1, 8, and 15 of a 28-day cycle for up to 6 total cycles
Key findings
- Twenty-six patients completed all 6 months of planned therapy
- Dose reductions occurred due to thrombocytopenia, fatigue, diarrhea, and infection
- SAEs occurred in 38% of subjects, and 5 deaths occurred in study participants
- Treatment failure rate was significantly improved versus the historical benchmark at 6 months: 28% versus 44%, P = 0.01
- Overall response rate (ORR): 40% (17/50) at 6 months
- OS: 92% at 6 months and 90% at 12 months
Joseph Pidala concluded that ixazomib therapy led to low treatment failure at 6 months, prednisone dose reduction, an ORR of 40% in patients with advanced cGvHD. Ixazomib was well-tolerated, 50% of patients completed 6 cycles of therapy. Dr. Pidala added that there are additional biomarker studies underway.
References