A Prospective, Multicenter Study of Bortezomib, Cyclophosphamide and Dexamethasone in Relapsed/Refractory Idiopathic Multicentric Castleman's Disease

【Introduction】Relapsed and refractory idiopathic Multicentric Castleman's disease (R/R iMCD) is a challenge for hematologists with poor prognosis. In the current study, we aimed to investigate the efficacy and safety of BCD regimen (bortezomib, cyclophosphamide, dexamethasone) in R/R iMCD patients.

【Methods】From 2017 to 2020, R/R iMCD patients who met the diagnostic criteria (Blood. 2017;129(12):1646-1657) were enrolled from Peking Union Medical College Hospital and Peking University First Hospital. BCD regimen (botezomib 1.3mg/m² weekly, cyclophosphamide 300mg/m² weekly, dexamethasone 40mg weekly out of a 28-day cycle) was administered for 9 cycles; after 9 cycles of BCD treatment, BD regimen (botezomib 1.3mg/m² twice a week, dexamethasone 20mg twice a week) was used as maintenance for the next 1 year. Treatment was discontinued after 1 year of maintenance or until treatment failure which was defined as death or progression of disease. Treatment responses were evaluated according to the treatment guidelines published recently (Blood. 2018;132(20):2115-2124). Biochemical, lymph node and symptomatic responses were evaluated which all contributed to the assessment of overall response. An overall CR (complete response) requires a complete biochemical, lymph node, and symptomatic response. An overall PR (partial response) requires nothing less than a PR across all categories, but not meeting criteria for CR. Overall SD (stable disease) requires no PD in any of the categories and not meeting the criteria for CR or PR. An overall PD (progression of disease) occurs when any category has a PD.

【Results】Data from 20 patients who were followed for at least 6 months were analyzed. The median age was 42 years (range 22-65 years), with a male: female ratio of 1.5:1. Six patients were defined as ‘refractory’ and fourteen patients were classified as ‘relapsed’. ALL patients (n=20) received BCD regimen and was followed every three months. As for biochemical response, 75.0% (n=15) achieved PR; 15.0% (n=3) were assessed as SD; 10% (n=2) were evaluated as PD. As for lymph node response, 5% (n=1) achieved CR and 75.0% (n=15) achieved PR; 10% (n=2) had SD while 10% (n=2) suffered from PD. As for symptomatic response, 85% (n=17) had PR (45%) or CR (40%); 15% (n=3) experienced PD. After incorporation of all the above evaluation results, 75.0% (n=15) patients achieved overall treatment responses (all were overall PR); 10% (n=2) patients were evaluated as overall SD; 15% (n=3) patients suffered from overall PD and were evaluated as treatment failure. As for safety issues, no patient suffered from Grade 3 or above adverse events and no patient died from treatment-related toxicity. With a median follow-up of 22 months (range 8-38), 40.0% (n=8) patients experienced disease of progression and two of them died from progression of iMCD. The estimated 1-year progression-free survival (PFS) and overall survival (OS) were 85.0% and 90.0% respectively (Fig 1).

【Conclusions】BCD regimen is an effective and safe treatment option for relapsed/refractory iMCD patients.

Fig 1. Kaplan–Meier survival analyses of relapsed/refractory iMCD patients receiving BCD regimen showing the overall survival and progression-free survival.