, according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.
Andrew D. Bowser/MDedge News
Dr. Franco Locatelli
The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.
Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.
Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.
Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.
In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.
The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.
The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.
Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.
Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.
In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.
There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.
However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”
The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.
SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.