David Fajgenbaum, MD, MBA, MSc: Treatment Options

What are potential treatment options for this patient?

Treatment for HHV-8-negative Multicentric Castleman Disease can be one of 4 categories. Corticosteroids are often used, B-cell depletion with a drug called rituximab, cytotoxic chemotherapy with combinations that often include Cytoxan, and finally anti—IL-6 therapy. The order that I went in is really the historical order. So corticosteroids were really the earliest options. Cytotoxic chemotherapy certainly came around at a later stage. But as we’ve gotten into the age of monoclonal antibodies rituximab is used more commonly, but anti–IL-6 therapy with siltuximab, which is the only FDA-approved therapy and EMA-approved therapy, is really the gold standard. It’s the only drug that has ever been tested in a randomized controlled trial to test the effectiveness against idiopathic or HHV-8-negative Multicentric Castleman Disease. So a patient like this with a very classic MCD scenario with clear systemic inflammatory symptoms with a systemic cytokine storm, like we’re seeing, should respond very well to anti–IL-6 therapy. So that would be the first choice.

Unfortunately, two-thirds of patients with Multicentric Castleman Disease will not respond to siltuximab, to anti—IL-6 therapy. For those patients, after trying siltuximab, if that does not work, then physicians should be considering things like rituximab on those targeted B-cells and also cytotoxic chemotherapy—cytoxan, etoposide, drugs that can eliminate the activated immune cells. At the heart of idiopathic Multicentric Castleman Disease is an activated immune system. We don’t yet know which immune cell is driving this cytokine storm, but, until that time, we use cytotoxic chemotherapy in really treatment refractory patients, so that way we can eliminate all immune cells.

But what I should also say is that patients that do respond to anti—IL-6 therapy will generally have a pretty quick or brisk response. So that the ones that will respond will usually begin to turn around pretty quickly after the first dose. It’s important to give it at least 1 to 2 doses before making a decision of continuing therapy, but it is generally a fairly quick response.

Multicentric Castleman Disease: Case 1

Mary is a 13-year old female who presents with a 10-month history of night sweats, fatigue, and weight loss. She presents to urgent care with complaints of flu-like symptoms. Her physical exam is notable for bilateral cervical lymphadenopathy (1-2 cm), mild splenomegaly, and mild edema. She has no neuropathy and no joint pain. She is referred to a hematologist to rule out lymphoma. Her medical history is unremarkable. Her family history is relevant for a mother with systemic lupus erythematous and father who died from colon cancer at 65 years old.

At the hematology office, the following laboratory abnormalities are noted:

• Anemia (Hgb 11 gm/dL), elevated CRP (35mg/L) and ESR (80mm/hr), elevated platelets (400,000/mK), Igs (IgG: 4500 mg/dL, IgM: 1500mg/dL, IgA: 300mg/dL).
• Negative ANA, negative dsDNA, anti-Smith and anti-phosholipid antibodies; monospot negative.
• PET scan showed generalized lymphadenopathy with a maximum SUV of 4.5; FNA of the Lymph node is uninformative. She was referred to a general surgeon for excisional lymph node biopsy.