Effect of Various Doses of Intravenous Polyclonal IgG on in vivo Levels of 12 Pneumococcal Antibodies in Patients with Chronic Lymphocytic Leukaemia and Multiple Myeloma

Abstract

Polyclonal intravenous IgG (IVIG) was administered as an infusion 6 times every 3 weeks (weekO, 3, 6, 9, 12, 15) in doses of 0.1, 0.4 and 0.8 g/kg BW to determine the dose causing an increase in 12 pneumococcal antibody types above the protective level of 200 ng/ml of antibody N. The dose of 0.4 g/kg BW was found to be optimal in patients with chronic lymphocytic leukaemia (CLL). From the first infusion onwards at least 80% of CLL patients had increases in all 12 antibodies. Five weeks after the last infusion the antibody levels were still elevated in 80% of patients with CLL. The dose of 0.8 g/kg raised all 12 antibodies in 53–73% of CLLpatients when assessments were made after each infusion. In multiple myeloma (MM) patients, 73–82% and 73–91 % of patients had increased antibody levels, respectively, before and after the 4th–6th infusions at the 0.8 g/kg dose level. However, in only 45–50% of patients did the antibodies remain increased 2 weeks after the treatment at this dose. The dose of 0.4 g/kg caused antibody increases in only 30–50% of patients when measured before the 4^th–6th infusion. Serum IgG increased significantly only in the CLL patients, whereas in the MM patients it was high from the beginning owing to the disease. Therefore, the pneumococcal antibody levels were a better marker for the purpose of dose finding. The dosage recommendation in CLL is 0.4 g/kg every 3 weeks until week 12, when steady state is reached. The maintenance dose is 0.4 g/kg every 5 weeks. In MM patients, who have a faster elimination rate of antibodies, the recommended loading dose is 0.8 g/kg, followed by 0.4 g/kg every week as a continuous treatment. Treatment with IVIG in CLL and MM was generally well tolerated. Only 25% of patients experienced minor side-effects, the most frequent being febrile reactions, shivering and headache.

A Canadian Perspective on the Use of Immunoglobulin Therapy to Reduce Infectious Complications in Chronic Lymphocytic Leukemia

“…Similar results have been observed in dose evaluation studies in secondary immunodeficiency disorders, suggesting the need for regular medical evaluation of patients 20,41 .…”

“…In studies examining ivig, the initial dose has ranged from 100 mg/kg to 800 mg/kg or a total dose of 10-24 g per infusion. The study by Sklenar et al 41 found the ideal dose to be 400 mg/kg every 3 weeks until a steady state is reached, followed by a maintenance dose of 400 mg/kg every 5 weeks. However, the study by Boughton et al 20 that used a dose of 18 g every 3 weeks found that, by increasing the dose in patients with breakthrough infections, 50% were kept infection-free.…”

“…In addition to variabilit y in dose, frequency of treatment has also varied, with igrt being given every 3 weeks in five studies and every 4 weeks in four studies (Table ii) 20,21,[39][40][41][42][43][44][45] . With respect to duration of therapy, most studies have been given ivig for a period of 1 year (Table ii) 20,21,39,40,42,43 .…”

Secondary antibody deficiencies

“…Intravenous immunoglobulin was found to be effective at reducing the incidence of bacterial infections [23][24][25][26], although no effect on overall mortality has been reported [27]. A starting dose of 400 mg/kg every 3 weeks was suggested [28]; however, evidence in the context of CLL [29] and primary antibody deficiencies [30] suggests that the dose may need to be altered in individual patients with the aim of preventing breakthrough infections and progression of structural lung disease. Although the cost-effectiveness of replacement immunoglobulin has previously been questioned in this setting [31], it is likely that rigorous patient selection, the increasing use of subcutaneous immunoglobulin in home therapy programmes and improved patient survival will have altered the cost-benefit ratio, although this remains to be formally assessed [21 & ].…”

Immunization in cancer patients: Where we stand

“…In a similar approach, oseltamivir prophylaxis given for 12 weeks has been shown to reduce culture-or PCR-confirmed influenza infection in solid organ and SCT recipients [80]. Finally, patients with hypogammaglobulinemia such as CLL or myeloma patients, and especially those who do not respond to vaccines, may benefit from immune globulines [81,82].…”