Potential Opportunity for Drug Discontinuation in Idiopathic Multicentric Castleman Disease: Evaluating the Efficacy of TCP Protocol
Authors: Dang Yue , Gao Yuhan , Li Siyuan , Zhang Lu , Li Jian 
Published: December 2024

Introductions: Remarkable strides forward in the field of idiopathic multicentric Castleman disease (iMCD) have been witnessed in recent years. The first ever treatment consensus formulated by the Castleman Disease Collaborative Network (CDCN) in 2018 advocates the use of monoclonal antibodies (mAbs) that target the IL-6 signaling pathway, including siltuximab and tocilizumab, and has significantly improved survival rates. However, significant challenges persist, as anti-IL-6 mAb therapy requires frequent and indefinite intravenous infusions, is financially burdensome, and may not be accessible globally. In this context, Zhang et al.‘s introduction of the oral Thalidomide-cyclophosphamide-prednisone (TCP) regimen stands out as a promising alternative (Blood. 2019;133(16):1720-1728.). With a high response rate and a cost-effective profile, this regimen has garnered favor and has subsequently been incorporated into the National Comprehensive Cancer Network (NCCN)‘s treatment guidelines for iMCD. Notably, unlike the lifelong commitment required with anti-IL-6 mAbs, the TCP protocol suggests the possibility of discontinuation after two years of treatment. This study aimed to investigate whether the TCP regimen can offer patients with iMCD the opportunity for drug discontinuation.

Methods: This single-center, retrospective study enrolled patients with newly-diagnosed iMCD between July 2015 and Dec 2021 who initiated the TCP treatment and subsequent thalidomide maintenance for a total of 2 years (TCP regimen for 1year and thalidomide (T) monotherapy for 1year). The diagnostic criteria for iMCD were based on the CDCN consensus. The primary endpoint of the study is the progression-free survival (PFS) after drug withdrawal. Response was defined according to the CDCN criteria (symptomatic response and biochemical response). Patients were followed until March 2024.

Results: 19 patients were enrolled in this study. The median age at the initiation of TCP was 38 (15-70) years, with a male to female ratio of 11:8. All of the enrolled patients were treatment-naive, and five were evaluated as severe iMCD. All patients discontinued therapy for iMCD after two years of TCP-T treatment. Upon drug withdrawal, all patients achieved symptomatic and biochemical responses, among whom 13 (68.4%) attaining complete response (CR) while others (31.6%) were evaluated as partial response (PR). The median follow-up duration post-discontinuation was 45.9（range 1.4-81.5）months. During the final follow-up, 16 patients remained in a treatment-free state, whereas 3 patients who had PR at drug discontinuation experienced disease progression with recorded progression times of 1.4, 6.2, and 46.7 months after thalidomide discontinuation, respectively. Of them, two subsequently transitioned to the next line of therapy, while the third patient restarted thalidomide-based treatment and achieved response again. All patients who achieved CR at the time of drug discontinuation did not suffer from disease progression with a median follow up time of 45.9 months. The median PFS had not yet been reached due to few progression events, yet the estimated 3-year PFS rate (after drug discontinuation) were 88.4 (74.5-100) %. Additionally, no fatalities were reported throughout the study period.

Conclusions: The TCP regimen might bring a chance for newly-diagnosed iMCD patients to discontinue treatment.