CDCN Treatment Discoveries and Repurposing Advances

Because of your support, the Castleman Disease Collaborative Network (CDCN) is fundamentally changing treatment options for and saving the lives of children and adults with Castleman disease (CD). Together, we’re providing hope where there was none before. We’re excited to share with you the highlights of our achievements in research! We will continue to update this page with our research progress as it becomes available.

6 New Medications Identified and Advanced as Treatments!

We supported the initial approval of siltuximab, recommend it as a first-line treatment in our updated guidelines, and continue to provide support through a study to help maintain its approval in Europe.

We discovered that sirolimus may be an effective therapy, succeeded in treating patients effectively, and subsequently launched a clinical trial. The first iMCD patients were treated with sirolimus in 2014, and the NIH-funded clinical trial launched in 2019. Treatment guidelines were updated in 2018 to include this therapy.

We discovered that ruxolitinib may be effective, succeeded in treating the first couple of patients effectively, and are now working to launch a clinical trial. The first iMCD patients were treated in 2021, and the first patient treated with ruxolitinib has been in remission for more than two years.

We collaborated on a clinical trial in the Annals of Hematology indicating that rituximab should be considered for treatment of iMCD in siltuximab-refractory cases and in cases where siltuximab is unavailable. This therapy was included in the iMCD treatment guidelines in 2018.

We collaborated on a clinical trial in 2022 indicating that velcade-dexamethasone-thalidomide can be utilized as a second- or third-line treatment.

We collaborated on a clinical trial in 2019 indicating that thalidomide-cyclophosphamide-prednisone can be utilized as a second- or third-line treatment.

10 Additional Treatments Have Been Identified for Further Investigation!

Evidence from a study we collaborated on identified cases of UCD with an MCD-like inflammatory state which suggested common biological behavior. As such, while siltuximab has been traditionally utilized first-line  in the treatment of iMCD, it has been identified as a potential treatment for investigation in the context of unresectable unicentric Castleman disease (UCD) and added to international evidence-based guidelines.

Rituximab has demonstrated potential in iMCD as a second- and third-line treatment and is actively used in cases of iMCD where siltuximab is ineffective or unable to be utilized. However, it is being actively investigated as a therapy in the setting of unresectable UCD and discussed in corresponding international evidence-based guidelines for UCD by an expert committee convened by the CDCN.

Embolization, a process wherein blood vessels that feed a mass are obstructed, is being actively investigated as an alternative to surgery in cases of unresectable UCD. One of our CDCN co-founders collaborated on a study in which several patients with unresectable UCD were treated with embolization. It is discussed and incorporated in the most recent international guidelines for UCD published in 2020.

We collaborated on a study that demonstrated increased activation of the complement system, a part of the immune system, in samples from patients with UCD and iMCD. Eculizumab, a potent complement inhibitor, has been identified as a potential therapeutic target for iMCD.

We collaborated on a study regarding the genetic basis for iMCD-TAFRO which suggested mutations in MEK can sensitize some iMCD patients to MEK inhibitors. MEK inhibitors like trametinib are suggested to benefit certain subsets of patients with iMCD and are an area for investigation.

In a study we conducted, we found that there is increased mTORC2 expression in lymph nodes of patients with iMCD-TAFRO. This has supported the investigation of an inhibitor such as sapanisertib which targets both mTORC1/mTORC2 for the treatment of iMCD.

We identified the protein CXCL13 is prominently up-regulated in iMCD and can also help predict a patient’s likelihood of responding to siltuximab. The utility of anti-CXCL13/CXCR5 therapies as a treatment for iMCD is an area for active investigation.

Through the collaborative efforts at Every Cure, artificial intelligence was used to guide the discovery of adalimumab as a potential treatment for iMCD. It was used to successfully treat the first patient with iMCD that was refractory to existing treatments.

We discovered that increased interferon gamma signaling is implicated in iMCD and that inhibitors of interferon gamma signaling, such as emapalumab (Gamifant), may be investigated as potential treatments.

We collaborated on a study that found that there is an increased type I interferon response associated with flares in iMCD-TAFRO subtype. Inhibitors of the type I interferon response, including anifrolumab, have potential for the treatment of iMCD.


While the CDCN has made remarkable progress, nearly 50% of children and adults with CD don’t respond to any of the standard therapies uncovered to date. Many are still suffering and losing their lives to this rare and often deadly disease. We will continue our relentless pursuit until there is an effective treatment, and ultimately a cure, for every single individual with CD. To find out more about how to support research for CD, please visit the “Get Involved” page on our website. With your support, we know we can achieve our goal!

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