Malignancy in neuromuscular patients on chronic IVIG

Abstract

Background: Intravenous immunoglobulin (IVIG) has been widely used to treat immune-mediated neuromuscular disorders. The relationship between IVIG and cancer is unclear. Preclinical studies have suggested that IVIG may influence cellular mechanisms pertinent to cancer development. This hypothesis is supported by clinical evidence, predominantly through case reports, although these findings are limited in scope and methodological rigor.

Methods: A retrospective review was conducted on patients receiving chronic IVIG treatment for Myasthenia Gravis (MG) and chronic immune demyelinating polyradiculoneuropathy (CIDP), at our tertiary medical center between 2000 and 2023.

Results: We identified 436 patients with MG and 102 patients with CIDP. Patients were divided into IVIG and non-IVIG treated in each of the disease groups. Seventy-five and 64 patients received IVIG in MG and CIDP groups, respectively. Cancer incidence was counted if it appeared at least 1 year after the diagnosis of MG or CIDP. In the MG group, cancer incidence was 12 / 75 (16%) among IVIG-treated patients compared to 87/350 (25%) in the MG-non-IVIG group (p = 0.09). Excluding mild MG cases, who were treated only by pyridostigmine, cancer incidence in the MG-non-IVIG group increased to 72/250 (28.8%), significantly higher than in the IVIG-MG group, p = 0.01. For CIDP patients receiving IVIG, incidence of cancer was 6/59 (10%), while in the non-IVIG-treated CIDP group, it was 9/34 (26%) (p = 0.03). Analyzing all IVIG-treated patients together (of both disease groups) showed a negative correlation between "time on IVIG treatment" and cancer (p = 0.001). Using logistic regression, we observed a negative coefficient for IVIG exposure (-0.03, p = 0.004), indicating that an increase in time from diagnosis is associated with a decreased likelihood of developing cancer in the IVIG-treated group.

Conclusion: Chronic IVIG therapy may be associated with a reduced incidence of cancer, particularly among patients with CIDP. Additionally, we found a negative correlation between duration of IVIG treatment and cancer incidence, suggesting a potential protective effect of long-term IVIG exposure. To our knowledge, this is the first study to explore the relationship between sustained IVIG therapy and long-term cancer risk in neuromuscular autoimmune diseases.

Keywords: CIDP; IVIG; Myasthenia Gravis; autoimmune disorders; cancer.

Figure 1

Schematic view of the study. Patients were investigated regarding the incidence of cancer in each of the disease groups (MG and CIDP). The date of autoimmune disease diagnosis was established as time zero for the purpose of our analysis. The dashed red arrow represents the time interval of cancer investigation (after at least 1 year of zero time). Red-colored Individuals represent patients with a cancer diagnosis while those who are green colored did not develop any kind of cancer.

Figure 2

The effect of IVIG on cancer incidence in each of the disease groups. (A) Cancer incidence is presented for each of the disease groups with or without chronic IVIG treatment. The X-axis represents the patient’s group while the Y-axis enumerates cancer incidence during the time interval after MG/CIDP diagnosis. In both disorders, the IVIG group had lower cancer incidence in the post-diagnosis time compared with the non-IVIG groups (p = 0.09 and p = 0.03 for MG and CIDP, respectively). (B) Scatter Plot of Cancer Occurrence by Time from Diagnosis and IVIG Exposure. This scatter plot illustrates the relationship between the time from diagnosis (in years) and the occurrence of cancer, with data points representing individual patients in both of the disease groups MG and CIDP, combined. The x-axis shows the time from diagnosis, while the y-axis indicates cancer occurrence (0 = No cancer, 1 = Cancer). Patients are categorized by their IVIG exposure status: those who received IVIG (IVIG = 1) and those who did not (IVIG = 0). Each point is color-coded based on IVIG status.

Figure 3

Box plot of time under IVIG treatment until cancer development or last follow up for patients who developed cancer vs. those who did not. This box plot compares the distribution of time under chronic IVIG treatment between patients who developed cancer (red) and those who did not (blue). The y-axis represents the time in years under IVIG treatment until cancer diagnosis or last follow up (if no cancer developed). The plot shows the median, quartiles, and outliers for each group. Patients who did not develop cancer (blue) generally received IVIG for a longer time (median around 10 years), while those who developed cancer (red) received IVIG treatment for shorter time durations (median around 2 years). Outliers are indicated by dots outside the whiskers.