Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Intravenous immunoglobulin reduced infections in multiple myeloma

ACP J Club. 1994 Sept-Oct;121:32. doi:10.7326/ACPJC-1994-121-2-032


Source Citation

Chapel HM, Lee M, Hargreaves R, Pamphilon DH, Prentice AG, for the UK Group for Immunoglobulin Replacement Therapy in Multiple Myeloma. Randomised trial of intravenous immunoglobulin as prophylaxis against infection in plateau-phase multiple myeloma. Lancet. 1994 Apr 30;343:1059-63.


Abstract

Objective

To evaluate the effectiveness of intravenous immunoglobulin (IVIg) in preventing infections in patients with multiple myeloma.

Design

Randomized, double-blind, placebo-controlled trial with a maximum follow-up of 1 year.

Setting

9 hospitals in the United Kingdom.

Patients

A prevalence sample of 83 patients (mean age 66 y, 51% men) with multiple myeloma who were fit enough to receive infusions and were expected to complete ≥ 6 months of treatment. Exclusion criteria were anaphylaxis to a blood product, immunoglobulin therapy within the past month, or total selective deficiency of serum IgA. Patients did not receive prophylactic antibiotics in the 2 weeks before entry and were not expected to during the study.

Intervention

Patients were allocated to receive IVIg, 0.4 g/kg (n = 42), or an equivalent volume of placebo, 0.4% albumin (n = 41), every 4 weeks for 12 months. Infusions of IVIg were delayed if an infection was present. Patients were stratified into the 2 treatment groups according to their serum nonparaprotein immunoglobulin level.

Main outcome measures

Severity and type of infection.

Main results

The median time from diagnosis was 14.5 months in the IVIg group compared with 18 months in the placebo group. 138 episodes of infection occurred during 919 patient-months at risk; 57 were serious, 19 in the IVIg group compared with 38 in the placebo group (95% CI for the 0.039 difference in infections per patient-month 0.007 to 0.071). No episodes of septicemia or pneumonia occurred in patients receiving IVIg compared with 10 episodes in patients receiving placebo (P = 0.002). 6 episodes of chest infection occurred in patients receiving IVIg compared with 18 episodes in patients receiving placebo (P = 0.01). IVIg protected against recurrent infection in the patients who were at risk for the full year (P = 0.021). IVIg also delayed the time to the first infection (P = 0.008). Mild adverse reactions were seen in 12% of IVIg infusions and in 5% of placebo infusions.

Conclusion

Intravenous immunoglobulin protected against life-threatening infections and reduced the risk for recurrent infections in patients with multiple myeloma in the stable phase.

Source of funding: Baxter Healthcare.

For article reprint: Dr. H.M. Chapel, Department of Immunology, John Radcliffe Hospital, Oxford 0X3 9DU, England, United Kingdom. FAX 44-865-742-180.


Commentary

Infections occur in patients with myeloma at presentation and after chemotherapy. Patients with objective responses to chemotherapy have a decreased risk for infection during this stable disease phase. Infections in patients with myeloma are secondary to suppression of normal humoral antibody responsiveness.

In an earlier prospective study, biweekly intramuscular injections of immunoglobulin failed to decrease infection rates (1). Chapel and colleagues are the first to present a controlled study showing a benefit from prophylactic IVIg. They studied a select subset of patients with response to chemotherapy, high performance status, and life expectancy of ≥ 6 months. 64 of their 83 patients were studied for plateau-phase myeloma (no substantial increase of paraprotein over 6 months). 44 of these 64 patients (69%) met this criterion. Prophylactic IVIg produced a statistically significant decrease in life-threatening infections, defined as septicemia or pneumonia. The patients who benefited were those who responded poorly to pneumococcal vaccination. This was only 43% (23 of 54) of the patients studied for antibody response. As the authors noted, "There was no significant protection (P = 0.65) in those patients who had demonstrated a good Ig response just before study." If patients with myeloma were treated in our center with Chapel and colleagues' program, the cost of IVIg therapy for 12 months (the duration of their study) for a patient weighing 70 kg would be $25 824.

Although the study by Chapel and colleagues showed a statistically significant protection against life-threatening infections by the use of IVIg, the practice should not be extended to all patients. Patients for whom prophylactic IVIg is being considered should be tested for their response to pneumococcal vaccine. Only patients with stable disease who are poor responders to pneumococcal vaccine should be treated with this program of prophylactic IVIg.

Phillip Periman, MD
The Don & Sybil Harrington Cancer CenterAmarillo, Texas, USA


Reference

1. Salmon SE, Samal BA, Hayes DM, et al. Role of gamma globulin for immunoprophylaxis in multiple myeloma. N Engl J Med. 1967;277:1336-40.