https://orcid.org/0000-0002-0308-6458
TO THE EDITOR:
We commend Carrillo de Albornoz et al for contributing to evidence regarding immunoglobulin replacement therapy (IgRT) in patients with chronic lymphocytic leukemia (CLL). Hypogammaglobulinemia is common in CLL, and infections contribute to a sizable proportion of CLL-related deaths.1 Despite its widespread uptake, evidence for IgRT is limited and largely from small studies conducted in the chemotherapy era.2,3
The authors found regular IgRT was not associated with reduced infection-related admissions,1 which suggests ineffectiveness in patients with hypogammaglobulinemia. However, we urge caution in drawing conclusions from these data alone.
Patients with serious infections were more likely to commence IgRT within 30 days, suggesting that those receiving IgRT had a higher baseline infection risk. The ability of IgRT to ameliorate infection is likely to be influenced by factors such as lung pathology and baseline and postreplacement immunoglobulin levels, as well as the delivery of CLL-directed therapy.
Patients receiving IgRT were more often diagnosed before 2015 and treated with chemoimmunotherapy, rather than newer agents. The declining use of chemoimmunotherapy today limits generalizability.
Soumerai et al4 reported an association between IgRT usage and infections and between IgRT use and antimicrobial use in a before-and-after analysis. Their IgRT usage rate (6.5%) was lower than that in the present study (12.1%), suggesting that prescribing variability influences outcomes. However, regression to the mean could exaggerate apparent benefits because IgRT was likely commenced during periods of high infection rates and subsequent declines may reflect natural fluctuation rather than treatment effect.5
We agree that further research is needed to clarify the causal relationship between IgRT and infections. Given the increased mortality among patients with serious infections, robust evidence is essential before altering clinical practice. This question can best be answered in a randomized trial. Although IgRT is widely available, designing a sufficiently powered study to identify the patients with CLL who benefit from this therapy will require strict inclusion criteria and international collaboration.
Another important question is when to stop IgRT. The RATIONALISE trial (ACTRN12622000359730) is evaluating cessation vs continuation of IgRT, with or without prophylactic antibiotics.
Contribution: S.O. and R.S. wrote and edited the manuscript and approved the final version.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Stephen Opat, Clinical Haematology, Monash Medical Centre, Level 3, 246 Clayton Rd, Clayton, VIC 3168, Australia; email: stephen.opat@monash.edu.
