Long‐term remission in HIV‐negative patients with multicentric Castleman's disease using rituximab

Abstract

Multicentric Castleman's disease (MCD) is an indolent lymphoproliferative disorder. The pathogenesis of MCD has not been established, and its treatment remains uncertain. Several authors have described the relationship of human herpes virus type 8 (HHV-8) to MCD in human immunodeficiency virus (HIV)-positive patients. Recently, anti-CD20 monoclonal antibody (rituximab) is increasingly being used to treat HIV-positive MCD; although it is uncertain whether rituximab is effective for HIV-negative patients with MCD. To explore the benefit of rituximab for HIV-negative patients with MCD, we describe the clinical and biologic course in three HIV-negative patients with MCD, and examined the relationship of HHV-8 infection to HIV-negative MCD. Their polymerase chain reaction analyses for the HHV-8 sequence in peripheral blood were negative, and there was no relationship between HHV-8 infection and symptoms of HIV-negative MCD. Two of three patients (66%) achieved a near complete remission with no clinical symptoms due to MCD with a follow-up of 16-40 months after rituximab administration. One of the three patients presented no clinical remission of MCD after rituximab administration, although a significant decrease of inflammatory parameters was observed. These findings suggest that rituximab treatment may be an appropriate first-line therapy for HIV-negative MCD.

HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy

“…85,86 Rituximab, which is a frequent first-or second-line therapy in iMCD, is only partially effective and typically does not provide long-term disease control. [87][88][89] Cytotoxic lymphoma-based chemotherapies (eg, cyclophosphamide, doxorubicin, vincristine, and prednisone) induce responses in a large portion of the most severely ill iMCD patients by eliminating a large portion of hypercytokine-secreting cells, but relapses are common and side effects are significant. 90,91 Over the last decade, treatments directly targeting IL-6 have been used.…”

Remissions of different quality following rituximab, tocilizumab and rituximab, and allogeneic stem cell transplantation in a patient with severe idiopathic multicentric Castleman’s disease

“…Although encouraging reports and single arm trials on rituximab in HMCD patients exist [2,3,8], published experiences in iMCD are scarce, comprising, to our knowledge, four reports on collectively six patients [5][6][7]9]. Four achieved CRs of at least 14-40 months, while one improved clinically and stabilized on maintenance chemotherapy for at least 10 months [6,7,9].…”

“…Four achieved CRs of at least 14-40 months, while one improved clinically and stabilized on maintenance chemotherapy for at least 10 months [6,7,9]. The sixth patient responded, but succumbed to preexistent end-stage cardiac amyloidosis 2 months after initiation [5].…”

“…HIV and HHV8 serology and PCR were negative. Nevertheless, we treated the patient with 4 cycles of weekly rituximab (375 mg/m 2 ), known to induce remissions in HMCD [2,[5][6][7]. In January 2009, final examination established clinical, laboratory ( Fig.…”

A woman with rheumatoid arthritis, Sjögren's Syndrome, leg ulcer, and significant weight loss

“…However, in Castleman's disease, the response with tocilizumab is temporary due to the emergence of neutralizing antibodies (50). The immunopathogenic role of CD20-positive B cells in RA and Sjö gren's syndrome is documented, and in Castleman's disease correlates with a near-complete response of the hyaline vascular type to rituximab (51)(52)(53). In RA patients who responded inadequately to TNF, rituximab is an alternate disease-modifying antirheumatic therapy, and in patients with Sjö gren's syndrome, small studies report equivocal efficacy, with improvement in individual disease parameters in the early stages of treatment (54,55).…”