Guess the Diagnosis: Case 1 - Episode 5
What are potential treatment options?
Dr. David Fajgenbaum, Perelman School of Medicine, University of Pennsylvania, says HHV-8negative MCD has been treated with corticosteroids, rituximab (Rituxan), anti-IL-6 therapies, and/or chemotherapeutic agents derived from the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen. Corticosteroids may temporarily control symptoms, but patients usually relapse on tapering, and sustained high steroid doses are not feasible. Rituximab has not been systematically evaluated in iMCD, and the limited number of case reports available suggests that patients often relapse with single-agent rituximab. A course of rituximab is often perceived as single-shot curative therapy, but there are no systematic studies that provide supportive evidence. Most of the published cases and series are confined to HIV and HHV-8–positive patients. However, there are some case reports of response, rituximab is widely used for other disorders, and its side effect profile is well known.
Monoclonal antibodies targeting IL-6 have been recently developed and subjected to the most rigorous clinical evaluation. A single-arm study of 28 Japanese patients on tocilizumab (Actemra) demonstrated a high response rate in symptoms, laboratory parameters, and reduction in lymphadenopathy. Siltuximab (Sylvant) was evaluated in a double-blind, placebo-controlled, randomized study using a control arm of best supportive care, including up to 60 mg of prednisone. The combined durable symptomatic and tumor response was 34%, and 50% of patients re- mained on drug for the duration of the study. This study provided the first placebo-controlled evidence for an iMCD therapy, and siltuximab is the only drug approved for iMCD by the US Food and Drug Administration (FDA). Both siltuximab and tocilizumab are safe and well tolerated. Elevations of cholesterol, mild thrombocytopenia, and occasional infusion reactions have been reported. Opportunistic infections with single-agent tocilizumab and siltuximab have not been reported, but both drugs may blunt the acute-phase reaction. The downside of IL-6targeting agents is that therapy is not curative, and in principle, lifelong relapses have been reported on cessation of therapy. In some patients, dosing intervals can be extended. Also, [some] patients do not respond, because IL-6 is not always the critical cytokine driving the disease. Immunosuppressants, immunomodulators, biologics, and cytotoxic chemotherapies, including cyclosporine, sirolimus, bortezomib, thalidomide, anakinra, interferon-α, cyclophosphamide, and etoposide, have been reported to have some success in case reports or in a small series of patients that do not respond to anti–IL-6 therapy.
This patient is symptomatic and requires therapy. Treatment of iMCD is also necessary to prevent transformation to lymphoma. The risk of developing lymphoma is estimated to be 10% to 15%, but there are no long-term longitudinal studies that have quantified the exact risk. Her symptoms are accompanied by abnormal laboratory parameters, which are in keeping with the presence of a proinflammatory syndrome likely driven by IL-6 because her IL-6 was substantially elevated. The patient was started on siltuximab 11 mg/kg every 3 weeks. Her symptoms and laboratory work rapidly normalized on therapy and were back to normal after 4 months. However, as anticipated, the resolution of her lymphadenopathy was slow, and complete resolution occurred after 18 months. Siltuximab neutralizes IL-6 and abrogates a major growth signal for lymphocytes and plasma cells in iMCD. However, it is not directly cytotoxic, which explains the slow involution of her lymphadenopathy.
Guess the Diagnosis: Case 1
Lisa B. is a 47-year-old female store owner from St. Louis, with a 10-month history of fatigue, night sweats, and weight loss.
Lisa’s pathology report shows the following findings:
In view of these findings, the hematologist orders further tests, which yield the following results: