Imbruvica Receives FDA Approval to Treat Adult Chronic Graft-Versus-Host-Disease Patients

The U.S. Food and Drug Administration (FDA) has approved Imbruvica (ibrutinib) to treat adult patients with chronic graft-versus-host-disease (cGVHD) who failed prior therapy, such as corticosteroids.

Stem cell transplants have been a standard of care for patients with blood disorders like leukemia and myeloma. Pre-clinical and early clinical studies suggest that it may also be a promising approach for patients with autoimmune disorders like systemic sclerosis.

Despite the promising results, however, 30 to 70 percent of patients who receive stem cell or bone marrow transplants soon develop cGVHD. This severe condition occurs when the transplanted immune cells recognize the recipient as foreign, triggering a life-threatening immune reaction.

Imbruvica, a drug already approved to treat several leukemias and lymphomas, blocks a protein called Bruton’s tyrosine kinase (BTK), which helps immune B-cells survive. Several animal studies indicated that B-cells may also drive cGVHD, which led researchers to see whether Imbruvica could prevent this serious condition.

The multi-center, open-label, single-arm PCYC-1129 Phase 1b/2 trial (NCT02195869) that led to FDA approval assessed the safety and efficacy of Imbruvica in 42 patients (median age 56) with cGVHD who failed first-line corticosteroid therapy.

Patients in the study had received bone marrow transplants due to acute lymphocytic leukemia, acute myeloid leukemia or chronic lymphocytic leukemia.

Patients had been diagnosed with cGVHD for a median time of 14 months before enrolling in the trial, and had received one to three cGVHD treatments before Imbruvica therapy. In addition, 88 percent of them had at least two organs affected with cGVHD at baseline — usually the mouth, skin, gastrointestinal tract or liver.

Trial results showed that Imbruvica induced a response in 67 percent of patients, including 21 percent complete responses and 45 percent partial responses. Responses lasted five months or longer in 48 percent of patients.

The most common adverse effects in cGVHD patients included fatigue, bruising, diarrhea, low platelet levels, muscle spasms, nausea, hemorrhage, anemia and pneumonia. One-quarter of patients discontinued treatment due to adverse reactions, the most common of which were fatigue and pneumonia. Another 25 percent had to reduce the dosage of Imbruvica.

“The FDA’s approval of Imbruvica in chronic graft-versus-host-disease after failure of one or more lines of systemic therapy addresses an area of high unmet medical need for patients and marks the first approved use for the therapy outside of blood cancers,” Lori Styles, GVHD program clinical lead at Pharmacyclics — a unit of AbbVie — said in a press release. “This approval is an indicator of what is possible with Imbruvica, and we remain excited about the clinical utility of Imbruvica in other disease areas.”