Idiopathic multicentric castleman disease - tafro: A potentially curable disease? Free

Idiopathic multicentric Castleman disease (iMCD) is a group of rare and sometimes life-threatening hematological disorders.The Castleman Disease Collaborative Network (CDCN) consensus for treating iMCD has been reached since 2018 and iMCD is recognized as an incurable disease as patients who respond to IL-6 targeted therapy are recommended to receive treatment indefinitely. However, as treatment experiences accumulate in this rare disease, iMCD-TAFRO, the sub-type which is regarded as having the most severe cytokine storm among all iMCD patients, might have chance to discontinue treatment and maintained remission.

This multi-center, retrospective study aimed to evaluate the possibility of maintaining long-term remission after treatment discontinuation in iMCD-TAFRO patients. iMCD-TAFRO patients who were diagnosed in Peking Union Medical College Hospital and the First Affiliated Hospital of Zhejiang University between Aug, 2015 to Nov, 2024 were analyzed. Patients who discontinued treatment and did not suffered from disease progression according to CDCN criteria after 3 months of drug discontinuation were enrolled for further analysis. These patients were followed until June 30, 2025 to see if they could enjoy long-term remission without treatment.

A total of 60 patients were enrolled for analysis. Of them, 33 patients were excluded due to death (n=9), still on planned treatment or switch to next treament (n=22), spontaneous remission without treatment (n=1) and lost to follow up (n=1). Twenty-seven patients, who discontinued treatment and still maintained treatment response, were enrolled with a male-to-female ratio of 15:12. All these 27 patients fulfilled the diagnostic criteria of iMCD-TAFRO and did not have disease progression at 3 months after drug discontinuation. The median age at diagnosis of iMCD-TAFRO was 49 years (range, 20-69). Twenty-two patients (81.5%) fulfilled the 'severe iMCD’ criteria of CDCN. Aside from one patient (3.7%) who was refractory to his first-line therapy and received a second-line of treatment before discontinuation of treatment, all other 26 patients (96.3%) were regarded as newly-diagnosed iMCD-TAFRO patients who received first-line treatment before drug discontinuation. All 27 patients received a median of 18 months (range, 2-41) of treatment targeting iMCD before discontinuation of his or her current line of therapy. With a median follow-up of 31 months (range, 12-108) after treatment discontinuation, only 4 patients (14.8%) suffered from progression of disease (PD) and the majority of patients (85.2%) maintained biochemical complete response (CR). Patients who suffered from PD had a significant lower pre-treatment CRP level than patients who maintained response (43.7±39.3mg/L vs. 126.4±62.5 mg/L, p=0.018). On the other hand, other parameters (gender, age, pathological sub-types, severe iMCD, constitutional symptoms, hemoglobin level, platelet level, renal function, immunoglobin G level) did not predict whether disease would progress. Notably, while all 27 patients achieved biochemical CR at the time-point of drug discontinuation, we did not observe significant impacts of different treatment approaches (myeloma-like, lymphoma-like, IL-6 targeted therapy, etc) or duration of treatment on the chances of achieving long-term remission. Among the 4 patients who experienced PD, the median time between drug discontinuation to disease progression was 9.5 months (range, 5-12). These patients all achieved treatment response with next line of therapy and were still on treatment for iMCD. Among the 23 patients who did not have disease progression, they all maintained biochemical CR without any treatment targeting iMCD-TAFRO by last follow-up. For the 27 patients who were enrolled in this study, the median progression free survival (PFS), which was defined as time from drug discontinuation to progression of disease, was not reached. The estimated PFS at 6 month, 1 year and 3 year were 96.3%, 85.2% and 85.2%, respectively. The progression of disease of the 4 patients all occurred within 1 year. All 27 patients stayed alive by our last follow-up date.

In conclusion, at least for a portion of iMCD-TAFRO patients, this distinct sub-type of iMCD could be regarded as a curable disease and 'indefinite’ treatment is not needed. For patients who achieved biochemical CR, an attempt of discontinuation of treatment might be worth trying.