What to do when first-line anti–IL-6 therapy fails in nonsevere idiopathic multicentric Castleman disease

This protocol applies to patients with idiopathic multicentric Castleman disease (iMCD) who do not have severe organ dysfunction and whose disease has not achieved an adequate response on first-line anti–IL-6 therapy.

Patient Profile

The target patient meets criteria for nonsevere iMCD: ECOG performance status below 2, eGFR at or above 30, hemoglobin above 8.0 g/dL, and no anasarca, ascites, pleural or pericardial effusion, or interstitial pneumonitis with dyspnea. These patients are typically managed in the outpatient setting and retain a good functional capacity without evidence of abnormal organ function.

First-Line Failure — Escalation Trigger

First-line anti–IL-6 monoclonal antibody therapy (siltuximab, or tocilizumab when siltuximab is unavailable) did not achieve the required targets: normalization of CRP, hemoglobin, albumin, and GFR, or meaningful improvement in fatigue, anorexia, fever, and weight. When these goals are not met, escalation to a second-line regimen is indicated.

Second-Line Approach

Second-line therapy is built around rituximab, with the option of adding steroids and, where clinically indicated, an immunomodulatory or immunosuppressive agent. The full selection criteria, sequencing, and management algorithm are in the complete protocol.

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References

DOI: 10.1182/blood-2018-07-862334

iMCD patients who are not severely sick are typically diagnosed in the outpatient setting and have a good performance status without evidence of abnormal organ function, whereas other patients are more symptomatic and often exhibit an IL-6–driven inflammatory response that interferes significantly with their ability to function and work.
Patients should be classified as nonsevere iMCD if the above criteria are not met.
Second-line therapy should comprise rituximab to which immunomodulatory/immunosuppressive agents (Figure 2), and steroids may be added.
Immunomodulatory/immunosuppressive agents for second- or third-line therapy include thalidomide, cyclosporine A, sirolimus, anakinra, or bortezomib, but we recommend consulting with an expert at this stage.

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