The disease course of Castleman disease patients with fatal outcomes in the ACCELERATE registry

David C Fajgenbaum, Sheila K Pierson, Karan Kanhai, Adam Bagg, Daisy Alapat, Megan S Lim, Mary Jo Lechowicz, Gordan Srkalovic, Thomas S Uldrick, Frits van Rhee, ACCELERATE Registry Team, David C Fajgenbaum, Sheila K Pierson, Karan Kanhai, Adam Bagg, Daisy Alapat, Megan S Lim, Mary Jo Lechowicz, Gordan Srkalovic, Thomas S Uldrick, Frits van Rhee, ACCELERATE Registry Team

Abstract

Castleman disease (CD) describes a group of rare, potentially fatal lymphoproliferative disorders. To determine factors associated with mortality in CD, we analysed data from deceased patients in the ACCELERATE registry and compared them with matched controls. We analysed demographic, treatment and laboratory data from all deceased CD patients, matched controls and a subgroup of idiopathic multicentric Castleman disease (iMCD) patients. Of the 140 patients in ACCELERATE with a confirmed CD diagnosis, 10 had died. There were 72 patients with confirmed iMCD; six were deceased. The deceased CD cohort had more hospitalisations per year, higher overall hospitalisations and more days hospitalised per month, and received more treatment regimens per year than the matched-control group. Analysis of laboratory values showed a significantly decreased absolute lymphocyte count at months 3 and 6 in the deceased cohort compared with controls. Among iMCD patients, there was a higher proportion of iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction and organomegaly) cases in the deceased group. The deceased iMCD group had significantly lower immunoglobulin M, international normalised ratio and platelet count. These data demonstrate that there may be differences between patients who have fatal and non-fatal outcomes, and provide preliminary suggestions for parameters to evaluate further.

Keywords: ACCELERATE; disease course; idiopathic multicentric Castleman disease; mortality; registry.

Conflict of interest statement

David C. Fajgenbaum has received research funding for the ACCELERATE registry from EUSA Pharma and consulting fees from EUSA Pharma, as well as study drug from Pfizer for a clinical trial of sirolimus, and holds pending provisional patents for “Methods of treating idiopathic multicentric Castleman disease with JAK1/2 inhibition” and “Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease.” Karan Kanhai is an employee of EUSA Pharma. Megan S. Lim received honoraria for participation in advisory board meetings for EUSA Pharma. Gordan Srkalovic reports speakers' bureau involvement with Takeda, Janssen Pharmaceuticals, Foundation Medicine and EUSA Pharma. Thomas S. Uldrick reports research support from Roche and Celgene, receives study drug for a clinical trial from Merck & Co, and is an employee of Regeneron. Frits van Rhee reports a consultancy relationship with Takeda, Sanofi Genzyme, EUSA Pharma, Adicet Bio, Kite Pharma and Karyopharm Therapeutics. All of the other authors report no competing interests.

© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Patients with iMCD in the deceased group (n = 6) and non‐deceased iMCD group (n = 66). (A), (B) and (C) show the mean ± SD of IgM, INR and platelet count respectively, in the deceased iMCD and non‐deceased iMCD groups. IgM, immunoglobin M; iMCD, idiopathic multicentric Castleman disease; INR, international normalised ratio; SD, standard deviation. *, significance
FIGURE 2
FIGURE 2
Repeated‐measures linear mixed model for monthly ALC in the deceased CD and matched‐control CD cohorts. Values in the graph represent mean ± SD. The values at month 0 show the ALC counts at the time of diagnosis. ALC, absolute lymphocyte count; CD, Castleman disease; SD, standard deviation. Note: p values changed over time, but only significant time points have been highlighted
FIGURE 3
FIGURE 3
Kaplan–Meier survival estimates for the Castleman disease patients with a Certification and Access Subcommittee‐approved diagnosis in (A), the general Castleman disease cohort (n = 139) and (B), the idiopathic multicentric Castleman disease cohort (n = 71). CI, Confidence interval; KM, Kaplan–Meier

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