Relapse Is Frequent for HIV-Associated Multicentric Castleman Disease, Despite Rituximab Treatment

Author’s Perspective

Study co-author Mark Bower, PhD: “The survival with [rituximab treatment] for HIV-associated MCD is remarkably good. Relapse following treatment still occurs, but every patient with disease relapse was successfully salvaged by repeat treatment. Also, despite the successful treatment of MCD, there remains a high risk of developing HHV8-positive NHLs.”

Though the introduction of rituximab in 2003 “revolutionized” the treatment of patients with HIV-associated multicentric Castleman disease (HIV-MCD) and improved prognosis, the disease appears to follow a relapsing and remitting clinical course even after primary therapy with rituximab, according to a study by Alessia Dalla Pria, MD, and co-authors from the Department of Oncology at The Chelsea and Westminster Hospital in London.

In this report, the researchers retrospectively analyzed longer-term outcomes of 84 patients (mean age = 42 years; range = 21-69 years) with HIV-MCD who were treated with rituximab-containing therapy at the National Centre for HIV Malignancy at The Chelsea and Westminster Hospital in London. Most patients (n=52) were treated with single-agent rituximab 375 mg/m2 administered intravenously every week for four weeks, while 32 patients received rituximab 375 mg/m2 in combination with etoposide 100 mg/2 both administered intravenously every week for four weeks.

Rituximab-treated patients had a five-year overall survival (OS) rate of 88 percent (95% CI 80-96).

After a median follow-up of 6.9 years, 80 patients achieved clinical remission; among these patients, two- and five-year OS rates were 96 percent (95% CI 91-100) and 92 percent (95% CI 85-99) respectively. Median CD19 count at relapse was 474/mL (15%), suggesting full recovery of B lymphocytes following firstline rituximab.

Seven patients died, though, and 19 percent (n=18/80) relapsed at least once after a median of 30 months (range = 3-124 months), highlighting the relapsing and remitting nature of this disease, the authors noted. They were not able to identify any clinical or laboratory factors, including sex, age, use of antiretroviral therapy, or CD4 counts, that were present at MCD diagnosis and would predict subsequent relapse.

Five of the patients with relapsed HIV-MCD had concomitant HHV8-associated lymphoma and MCD at relapse. The remaining 13 patients were re-treated with rituximab-containing therapy up to five times. The authors noted that the rate of second relapse was substantially higher (53% within 5 years of remission, at a median of 2.9 years) than occurred following the first remission (18%).

The risk of developing HHV8-associated lymphoma also was “significantly elevated” in this cohort, with an incidence of 11.4/1000 person-years, the authors noted. “The relatively low relapse rate and high salvage rates at relapse reduce the potential benefit of maintenance therapy.” They added, though, that the safety and efficacy of maintenance rituximab therapy needs to be investigated in a larger randomized trial.

The study is limited by its small patient population and retrospective, single center design.

Source: Pria AD, Pinato D, Roe J, et al. Relapse of multicentric Castleman’s disease following rituximab based therapy in HIV-positive patients: implications for maintenance treatment. Blood. 2017 January 17. [Epub ahead of print]