Routine Immunoglobulin G Testing Reduces Infections in Patients with Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia

Patients with non-Hodgkin lymphomas (NHLs) and chronic lymphocytic leukemia (CLL) who underwent frequent immunoglobulin G (IgG) testing to see whether immunoglobulin replacement therapy (IgRT) would be necessary for their condition had decreased odds of infection and less severe infections overall, according to the results of a study published in Blood Advances.¹

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Concurrently, those who underwent frequent testing and subsequently underwent IgRT had significant reductions in hypogammaglobulinemia, infections–including severe infections–and associated antimicrobials, according to the study authors.

Hypogammaglobulinemia is a common type of secondary immune deficiency (SID), which NHL and CLL are associated with and can be amplified by some treatment options like chemotherapy or immunomodulatory drugs. Hypogammaglobulinemia contributes to the high infection risk in these patients, which is a major driver of mortality in these populations.¹

IgRT is utilized to increase levels of IgG and improve a patient’s ability to overcome infection. Despite the importance of this treatment, there is a high degree of heterogeneity across guidelines regarding frequency of IgG testing, and many patients do not undergo regular IgG monitoring at diagnosis, during infection, or post-infection.¹

The investigators sought to address this unmet need and examine IgG testing patterns, as well as analyze the effectiveness of IgRT in reducing infection rates in patients with NHL and CLL.

This retrospective and observational study used clinical data from 8 hospitals in and around the Boston area between 2010 and 2023. The study population included 13,232 patients with NHL and 3960 patients with CLL, totaling 17,192 patients, the study authors wrote.¹

First, IgG testing during follow-up was assessed. In the NHL cohort, 51.2% (n = 6773) and 32.5% (n = 4306) had ≥ 1 or ≥ 2 IgG tests, respectively. Among patients who had ≥1 IgG test, 35.6% (n = 2411) of patients had hypogammaglobulinemia; at the initial diagnosis of NHL, IgG testing was performed in 16.6% of patients.¹

In the CLL cohort, 67.0% (n = 2652) and 47.2% (n = 1743) had ≥ 1 or ≥ 2 IgG tests during follow-up, respectively. Among those with ≥ 1 IgG test, 34.6% (n = 917) of patients had hypogammaglobulinemia. At the initial diagnosis of CLL, testing was performed in 29% of patients.¹

Next, treatment with IgRT among these patients was analyzed. Only 4.7% (n = 623) of patients with NHL received IgRT, while 6.5% (n = 259) of patients with CLL received the treatment. Most patients who received in IgRT in each subgroup (53.0% in NHL, 56.8% in CLL) received ≥ 2 administrations of IgRT, according to the study investigators.¹

In the cohort of patients who were administered IgRT, their hypogammaglobulinemia and IgG levels were analyzed in the 3, 6, and 12 months before and after they initiated IgRT. For patients with NHL, the median IgG levels at 3-, 6-, and 12-months post-index date was 521, 507, and 507 mg/dL, respectively, with pre-index levels of 337.5, 346.5, and 352 mg/DL (P < .0001) respectively.¹

Patients with CLL who utilized IgRT had median IgG levels at 3-, 6-, and 12- months post-index was 494, 491, and 499 mg/dL, respectively, compared with pre-index levels of 342.5, 355, and 359 mg/dL (P < .0001). In both the NHL and CLL cohorts, the prevalence of hypogammaglobulinemia was lower at each of the 3 follow-up points.¹

Among both the NHL and CLL IgRT cohorts, there were significantly lower odds of both infections overall and severe infections 3 months after IgRT initiation compared to 3 months before, according to the study authors. They noted that these findings were also consistent at the 6- and 12-month follow-up points.¹

“Within each disease cohort, patients with three or more IgG tests were more likely to have low IgG detected and also more likely to receive IgRT,” said Jacob D. Soumerai, MD, the study’s lead investigator. “These findings suggest that patients known to have low levels of IgG might be more likely to communicate recurrent minor infections to their hematologists, leading to improved IgRT use.”²

One of the main takeaways from these results, according to the study authors, is the wide variability in practice regarding IgG testing among hematologists. In each cohort, the number of tests per patient varied strongly; there were a large proportion of patients without any IgG testing at all during the study period.

“As the treatment landscape evolves for patients with CLL and NHL, a critical need exists to develop guidelines and consensus on SID monitoring and management,” the investigators concluded.¹

References

1. Soumerai J, Yousif Z, Gift T, et al. IgG testing, immunoglobulin replacement therapy, and infection outcomes in patients with CLL or NHL: real-world evidence. Blood Adv. 2024. doi:10.1182/bloodadvances.2024013073

2. EurekAlert! Reduced infections seen in CLL and NHL patients undergoing immunoglobulin testing and replacement therapy. Press release. Published June 21, 2024. Accessed June 27, 2024. https://www.eurekalert.org/news-releases/1048703