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.