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

Abstract

K E Y P O I N T S l The TCP regimen showed promising efficacy and safety to treat newly diagnosed iMCD.l Although more research is needed, the TCP regimen is an important treatment option, particularly when siltuximab is not available.Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder. The anti-interleukin 6 (IL-6) therapy siltuximab is not available everywhere, and is not effective for over one-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 a 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. The TCP regimen (thalidomide 100 mg daily for 2 years; oral cyclophosphamide 300 mg/m 2 weekly for 1 year; prednisone 1 mg/kg twice a week for 1 year) was administered for 2 years or until treatment failure. The primary end point was durable tumor and symptomatic response for at least 24 weeks. Twelve patients (48%) achieved the primary end point with no relapse, 3 patients (12%) demonstrated stable disease, and 10 patients (40%) were evaluated as treatment failure. Even when considering all patients, there were significant (P < .05) improvements in median symptom score, IL-6 level, hemoglobin, erythrocyte sedimentation rate, albumin, and immunoglobulin G. Among responders, the median levels of all evaluated parameters significantly improved, to the normal range, after treatment. The regimen was well tolerated. One patient died of pulmonary infection and 1 patient had a grade 3 adverse event (rash); 2 patients died following disease progression. Estimated 1-year progression-free survival and overall survival were 60% and 88%, respectively. The TCP regimen is an effective and safe treatment of newly diagnosed iMCD patients, particularly when siltuximab is unavailable. This trial was registered at www.clinicaltrials.gov as #NCT03043105

A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study

“…However, there are few truly effective therapies for iMCD, and its prognosis has remained mostly unchanged over the past 30 years [4, 18]. Recently, several new treatment modalities, including chemotherapy, rituximab, siltuximab, tocilizumab, anakinra (IL‐1RA agonist), thalidomide, and lenalidomide, have been used and, in some cases, shown efficacy [12, 15, 19–22]. However, these treatments have substantial toxicities and are costly.…”

“…Laboratory hallmarks include leukocytosis, anemia, thrombocytosis or thrombocytopenia, elevated erythrocyte sedimentation rate, increased C‐reactive protein (CRP) and fibrinogen, hypergammaglobulinemia, and hypoalbuminemia [9]. iMCD often responds to initial treatment but frequently relapses; thus, the treatment strategy varies from “watchful waiting” to high‐dose chemotherapy, and numerous treatment options have been proposed for patients with iMCD, but no effective regimen has been discovered [2, 10–12].…”

Acute Kidney Injury Caused by TAFRO Syndrome in a Chinese Patient: Efficacy of Long-Term Corticosteroids Combined with Bortezomib and Cyclophosphamide

“…Due to a scarcity of cases and a lack of understanding of the disease mechanisms, there is no standard treatment for TAFRO syndrome. The main therapeutic options include corticosteroids, immunosuppressive therapy, rituximab or rituximab-based therapy, anti-IL-6 therapies (tocilizumab and siltuximab), thalidomide combined with cyclophosphamide and prednisone, and plasma exchange [3,5,6,9,10,[19][20][21][22]. The Japanese TAFRO Research Group recommends high-dose steroids, tocilizumab, and cyclosporine A for TAFRO patients [7].…”

Diagnosis and Management of Castleman Disease

“…A thalidomide/cyclophosphamide/prednisone regimen is an additional option in patients with relapsed disease, 7 and can also be considered in the frontline treatment of patients with hyaline vascular iMCD, he said.…”