Immunoglobulin Replacement Therapy for Hypogammaglobulinemia in Multiple Myeloma Should Not Be Ignored

To the Editor,

The letter entitled “Invasive Aspergillosis and Candidiasis in a Patient with Plasma Cell Myeloma,” written by Khadwal et al. [1], as well as Yavaşoğlu’s [2] comment on it, published in recent issues of your journal, were quite interesting. Here we would like to highlight another critical issue that may be overlooked, which is the role of immunoglobulin replacement therapy (IgRT) for hypogammaglobulinemia in multiple myeloma (MM) in the prevention of invasive fungal infection. Khadwal et al. [1] reported that a 65-year-old woman diagnosed with immunoglobulin G (IgG) kappa MM 4 years previously had died of her illness within 5 days of admission to the hospital and that invasive fungal infections were found in this patient. We noticed that this patient had severe hypogammaglobulinemia at the time of her final admission, including IgG of 364 mg/dL (normal: 658-1837 mg/dL), IgM of <21.0 mg/dL (normal: 40-263 mg/dL), and IgA of 41.0 mg/dL (normal: 71-263 mg/dL). However, from our perspective, severe hypogammaglobulinemia was not temporarily induced, and there was a long period since the diagnosis or first chemotherapy of this MM patient.

As we know, the overall survival of MM patients has significantly improved since the introduction of bortezomib and lenalidomide. However, chemotherapy is significantly associated with myelosuppression or DNA synthesis inhibition, further impairing humoral or cellular immunity. These chemotherapies also significantly reduce Ig production and result in secondary immunodeficiency (SID) in MM patients. Therefore, MM patients who have received these chemotherapies are at a high risk of infection, and infections are still the main cause of morbidity and mortality in MM patients.

IgRT and prophylactic antibiotics are two main strategies for the care of patients with SID, especially secondary to hematological diseases [3]. Recent data demonstrated that MM patients receiving IgRT had a lower reduction in the use of antibiotics, fewer days of hospitalization, and fewer infections compared to patients not receiving IgRT [4]. Moreover, in our country, hematological SID specialists are still lacking, and IgRT for SID patients is not covered by health insurance, which results in a high infection rate among MM patients.

Thus, in this letter, we want to highlight another critical issue that may overlooked, which is the role of IgRT for hypogammaglobulinemia in MM in the prevention of invasive fungal infection. Moreover, monitoring Ig levels at diagnosis or after chemotherapy for MM could further enhance the surveillance of fungal infection risk and reduce the mortality rate in MM patients.