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Phase 2 study using oral thalidomide-cyclophosphamide-prednisone for idiopathic Multicentric Castleman disease

Lu Zhang, Ai-lin Zhao, Ming-hui Duan, Zhi-yuan Li, Xin-xin Cao, Jun Feng, Dao-bin Zhou, Ding-rong Zhong, David C. Fajgenbaum and Jian Li

Key points

  • Thalidomide-cyclophosphamide-prednisone regimen showed promising efficacy and safety to treat newly diagnosed iMCD.

  • Though more research is needed, the TCP regimen is an important treatment option, particularly when siltuximab is not available.

Abstract

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder. The anti-interleukin(IL)-6 therapy siltuximab is not available everywhere, and is not effective for over half of patients. Alternative treatment approaches are urgently needed. In the first iMCD clinical trial directed against a target other than IL-6 signaling, we investigated thalidomide-cyclophosphamide -prednisone (TCP) regimen in newly diagnosed iMCD patients. This single-center, single-arm, phase 2 study enrolled 25 newly diagnosed iMCD patients between June 2015 and June 2018 (registered on ClinicalTrials.gov: NCT03043105). The TCP regimen (thalidomide 100mg daily for 2 years; oral cyclophosphamide 300mg/m2 weekly for 1 year; prednisone 1mg/kg twice a week for 1 year) was administered for 2 years or until treatment failure. The primary endpoint was durable tumor and symptomatic response for at least 24 weeks. 12 (48%) patients achieved the primary endpoint with no relapse; 3 (12%) patients demonstrated stable disease; and 10 (40%) patients were evaluated as treatment failure. Even when considering all patients, there were significant (P< .05) improvements in median symptom score, IL-6 level, hemoglobin, ESR, albumin, and IgG. Among responders, the median levels of all evaluated parameters significantly improved after treatment to the normal range. The regimen was well tolerated. One patient died from pulmonary infection and one patient had a Grade 3 adverse event (rash); two patients died following disease progression. The estimated 1-year progression-free survival and overall survival was 60% and 88%, respectively. The TCP regimen is an effective and safe treatment for newly diagnosed iMCD patients, particularly when siltuximab is unavailable.

  • Submitted November 6, 2018.
  • Accepted February 1, 2019.