New Drug Brings Relief for Rare Disease

The investigative agent siltuximab shows promise in treating patients with multicentric Castleman’s disease— a rare lymphoproliferative disorder for which patients have few treatment options, researchers said here.

In an international trial, about 25 percent of patients treated with siltuximab achieved a durable complete response to their disease compared with none of the placebo patients (P=0.0037), said Raymond Wong, MBChB, MD, a radiation oncologist at Prince of Wales Hospital and the Chinese University of Hong Kong.

The median duration of complete symptom response was about 1.3 years; some patients have complete response for more than 2 years, Wong told MedPage Today during a press briefing at the annual meeting of the American Society of Hematology. “We are continuing to treat our patients as long as there are responses,” he said.

In the trial that enrolled 79 patients, 53 of whom were assigned to receive siltuximab, the researchers defined durable response as at least 18 weeks without symptoms or a reduction of tumor size. Wong reported that durable response was not seen in any patient on placebo taken on top of best supportive care while durable responses were observed in 34% of the patients on siltuximab (P=0.0012).

“These results are encouraging and reinforce the potential for siltuximab to be a new treatment for multicentric Castleman’s disease patients who previously had no approved treatment options,” Wong said. “These are very exciting results because none of the placebo patients achieved these durable responses.”

Multicentric Castleman’s disease affects multiple groups of lymph nodes. Although not technically a cancer, the disease can act like lymphoma. According to the American Cancer Society, people with the disease can experience serious infections, fevers, weight loss, fatigue, night sweats, and nerve damage that can cause weakness and numbness. Blood tests often reveal anemia. Wong noted, “This disease not only impacts a person’s quality of life, but it can be fatal.”

Wong said that the disease is driven by dysregulated interleukin-6. Siltuximab is a chimeric monoclonal antibody that binds with human IL-6 with high affinity and prevents IL-6 from interacting with the IL-6 receptor.

The patients in the study were about 48 years old, 66% were men; 39 percent were white and 48 percent were Asian; 93 percent were in ECOG Performance Status of 0-1; 58 percent had undergone at least one other treatment.

“This was the only multinational, randomized, double-blind, placebo-controlled study in multicentric Castleman’s disease,” Wong said. The researchers recruited patients from 36 sites in 19 countries. The rarity of the disease is attested to by the fact that just 79 patients could be recruited for the study over two years.

In addition to proving better than placebo in achieving durable responses, Wong said the median time to treatment failure for placebo patients was 134 days, but the median time to treatment failure in the siltuximab patients has not yet been reached (P=0.0084).

He also noted that hemoglobin increases to at least 15 g/L by week 13 of treatment had been achieved by none of the placebo patients but by 61 percent of the patients on siltuximab (P=0.0002).

Wong said the treatment was well tolerated with an adverse event profile similar to placebo, even though the siltuximab patients were on treatment twice as long as placebo patients. One patient on siltuximab experienced an anaphylactic reaction. The Grade 3 reaction required removing the patient from the study, he said.

Press conference moderator, Joseph Mikhael, MD, a hematologist at the Mayo Clinic in Scottsdale, Ariz., said, “I care for a number of patients with Castleman’s disease. This is a rare condition. We are starting to understand the mechanism which is interleukin-6. Roughly a third of patients not only had a response with this drug but had a durable response and were able to do so with minimal toxicity.

“We have so little to offer these patients and to have a drug like this that is seemingly efficacious and has so little toxicity is encouraging. I think there is a lot of enthusiasm for this,” he told MedPage Today.