Tag: Non-Hodgkin Lymphoma

SUMMARY: Castleman Disease (CD) also known as giant lymph node hyperplasia and angiofollicular lymph node hyperplasia is a disease of lymph nodes and related tissues and can be Unicentric (localized) or Multicentric. Younger individuals are more likely to have the localized form whereas older adults and those with HIV infection are more likely to have the Multicentric form. Unicentric CD only affects a single group of lymph nodes and curative resection of the affected lymph nodes is feasible. Multicentric Castleman Disease (MCD) behaves like a lymphoma and is classified as a lymphoproliferative disorder and requires treatment intervention. The number of people diagnosed with MCD has been increasing with the rising incidence of HIV infection. Even though retroviral therapies have improved survival in patients with HIV infection, this has not impacted the incidence of MCD. Approximately 50% of the MCD cases have been attributed to Kaposi's Sarcoma-associated Herpes Virus (KSHV), also known as HHV-8, a gamma herpes virus which is a causative factor for Kaposi's sarcoma and Primary Effusion Lymphoma, while the cause of the remainder of the MCD cases is unknown. There are three microscopic subtypes of CD – The hyaline vascular type which is localized (Unicentric) type, the plasma cell type which is more likely to be Multicentric, and the mixed subtype which occurs less often. The microscopic findings are less important when it comes to treatment whereas treatment is based on whether the disease is Unicentric or Multicentric. KSHV is closely associated with plasmacytic form of MCD while the hyaline vascular type is generally negative for KSHV. Patients with Multicentric CD usually experience fevers, night sweats, weight loss, fatigue as well as leukocytopenia, hypergammaglobulinemia, generalized lymphadenopathy and possible splenic involvement. It resembles angioimmunoblastic lymphadenopathy and the symptoms and signs have been attributed to dysregulated interleukin (IL)-6 production. Some patients with CD may have normal IL-6 levels and present with microcytic anemia without iron deficiency, which resolves after effective therapy. MCD is seen in patients with POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) and has been implicated in 10% of cases of paraneoplastic pemphigus. Based on the preliminary data demonstrating the efficacy of SYLVANT® (Siltuximab), a chimeric monoclonal antibody targeting human IL-6, in MCD patients, an international, multicenter, randomized phase II trial was conducted. Patients with Multicentric Castleman Disease (MCD) who were Human Immunodeficiency Virus (HIV) negative and Human Herpes Virus-8 (HHV-8) negative (N=79) were randomized 2:1 to receive SYLVANT® (Siltuximab) given every three weeks, as an IV infusion at a dose of 11 mg/kg along with Best Supportive Care (N=53) or Placebo plus Best Supportive Care (N=26). The median age was 48 yrs, 30% were on corticosteroids and 58% had prior systemic therapy. Primary endpoint was durable tumor and symptomatic response defined as PR or CR by independent review and improvement or stabilization in MCD-related symptoms for 18 weeks or more. Secondary endpoints included additional predefined efficacy measures and safety. The durable tumor and symptomatic response rates (Primary endpoint) were 34% versus 0% for the SYLVANT® and Placebo groups respectively (P=0.0012). With regards to secondary endpoints, tumor response rates were 38% versus 4% for the SYLVANT® and placebo groups, respectively (P<0.05), the median time to treatment failure was 134 days in those receiving placebo and had not been reached in the SYLVANT® (P=0.0084), an increase in the hemoglobin of at least 1.5 grams/dL at week13 in anemic patients was seen in 61% of the patients receiving SYLVANT® vs 0% in those receiving Placebo (P=0.0002). There were sustained decreases in C-Reactive Protein (a marker of IL-6 activity), ESR, and fibrinogen as well as an increase in albumin in the SYLVANT® group. The common adverse reactions (>10% compared to placebo) during treatment with SYLVANT® were pruritus, weight gain, rash, hyperuricemia and upper respiratory tract infections. The authors concluded that this is the first randomized study involving patients with Multicentric Castleman Disease, that has demonstrated significant efficacy with SYLVANT®, resulting in durable tumor and symptom responses and added clinical benefit. Wong RS, Casper C, Munshi N, et al. Abstract #505. ASH Annual Meeting and Exposition, 2013

SUMMARY: In this intriguing analysis, the authors reported the outcomes, when patients with low grade Follicular Lymphoma received maintenance RITUXAN® (Rituximab) beyond 2 years. The randomized, PRIMA (Primary Rituximab and Maintenance) study established that 2 years of RITUXAN® maintenance therapy after a RITUXAN® plus chemotherapy regimen, as first-line treatment for follicular lymphoma, significantly improves Progression Free Survival (PFS). The decision to give 2 years of maintenance RITUXAN® in the PRIMA study was arbitrary. It is estimated however that over 30% of the patients receiving 2 yrs of maintenance RITUXAN®, relapse at 3 years and beyond. The authors in this single institution study analyzed clinical data on 25 consecutive, unselected, treatment naïve patients with biopsy-proven diagnosis of Follicular Lymphoma. All these patients had a high tumor burden, with at least one indication for initiation of systemic therapy, which included B symptoms, cytopenia(s), bulky disease, disease progression, or impending organ damage. These patients achieved a Partial Response (PR) or a Complete Response (CR), after systemic induction treatment and subsequently received Maintenance RITUXAN® indefinitely or until disease progression. The median follow up was 5 years. The PFS in this group was 100% and 5 year overall survival was 82%. Forty five percent (45%) of the patients who achieved PR improved to CR on Maintenance RITUXAN® treatment. This benefit was accomplished with minimal toxicity with no additional complications related to hypogammaglobinemia. The authors concluded that Maintenance RITUXAN® beyond the arbitrary 2 years, is safe and may result in prolonged PFS in responding patients following chemoimmunotherapy. This provocative data begs the question whether maintenance RITUXAN® should be continued until disease progression rather than stopping at the 2 year arbitrary time frame. Yared J, Kimball A, Baer MR, et al. Clinical Lymphoma Myeloma and Leukemia 2013;13:253-257