Ibrutinib Salvage in Relapsed CLL After Allogeneic Transplantation

Conference Correspondent - ASH 2014 - CLL

The treatment of relapsed CLL with ibrutinib has been shown to result in high rates of PFS and OS, including in patients with del17p (Byrd JC, et al. N Engl J Med. 2013;369:32-42, 1278-1279). Ryan and colleagues now report the results of the use of ibrutinib as salvage therapy in 5 patients with CLL who relapsed 1 year to 8.5 years after allogeneic SCT and who never achieved >95% CD3 donor T-cell chimerism after the transplant (Blood. 2014;124. Abstract 1186).

Ibrutinib 420 mg daily was started 1 month to 2 years after clinical relapse. In 4 patients with pathologic lymphadenopathy before ibrutinib therapy, all experienced a 68% average reduction in lymph node size within 3 months of starting ibrutinib, and all 4 achieved undetectable MRD. One patient who achieved undetectable MRD was evaluated for donor T-cell chimerism; evidence of donor T-cell immune modulation, donor CD3 chimerism, and the resolution of oral and skin chronic graft-versus-host disease (GVHD) were all achieved, and the donor T-cells remain >1% of peripheral blood mononuclear cells, 8 months after the discontinuation of ibrutinib as a result of the attainment of negative MRD. In addition, the patient’s B-cells have diverse, low-frequency immunoglobulin H clonotypes.

These findings show rapid, sustained, and diverse immune reconstitution without CLL recurrence after the discontinuation of ibrutinib, and suggest that ibrutinib provides effective salvage therapy for patients with relapsed CLL after allogeneic SCT. Treatment with ibrutinib demonstrated promising donor immune modulation by promoting full donor chimerism and the resolution of chronic GVHD. The results of this study prompt additional clinical trials to determine the ideal duration of ibrutinib therapy after allogeneic SCT relapse and the role of ibrutinib maintenance after allogeneic SCT in these patients.