This was a retrospective longitudinal observational study using the data from the Mass General Brigham Research Data registry. We looked at the use of immunoglobulin replacement therapy in patients with multiple myeloma. The timeframe for this retrospective analysis was from January 1st 2010 until February 15th 2023.
What was the study design?
What we were looking at in this study was the use of immunoglobulin replacement therapy in patients with myeloma. We were specifically interested in seeing what the impact of using IVIG, or immunoglobulin replacement therapy, was on the risk of infection in patients. We know that infections are a significant comorbidity of patients with multiple myeloma so our goals were not only to look at the use of immunoglobulin replacement therapy but also the impact on infections and infection risk in this patient population.
What are the key results?
Of a possible 11,000 patients that were diagnosed with myeloma 6,062 patients were eligible from within that cohort. We excluded patients who had a prior diagnosis of primary immune deficiency, HIV, patients who had had a solid organ transplant and we also needed patients to have had at least three visits within our system to be eligible to ensure that we had appropriate longitudinal follow-up. Really what we found was that of those 6,000 patients 471 of those patients had received immunoglobulin replacement therapy at least once.
Then we next looked at the interval three months before and three months after to look at the relative immunoglobulin levels and also risk of infection. Of the total cohort, as I noted, 471 patients did receive immunoglobulin replacement therapy, which was about 8% of that cohort. It’s particularly noteworthy the timeframe in which this was done, this study came to a close before we really had significant usage of the FDA approved CAR T-cell products and bispecifics. As I mentioned, the endpoint of this study was February 15th 2023 and so what’s significant about this is just that even before we had these therapies which cause an even greater degree of hypergammaglobulinemia we see the relevance of this information.
The patients on this study, the majority, about 50%, had been treated with proteasome inhibitors; 43% immunotherapies including monoclonal antibodies like daratumumab, isatuximab and elotuzumab; 40% had received an immunomodulatory agent; about 36.5% alkylating agents; 34.8% stem cell transplant; 5.6% CAR T and 1% bispecifics. What we saw was that of the patients receiving immunoglobulin therapy, of those about 50% received more than two of these administrations. So from the time of a myeloma diagnosis to the onset of receiving immunoglobulin replacement therapy was approximately 32 months. Then what we see is in those patients receiving multiple doses of IVIG it was an interim of about 3.1 months between those doses.
The most important thing that we took away from this was that the odds of infection and particularly severe infections and antimicrobial use were significantly lower after the initiation of immunoglobulin replacement therapy. This included all infections, all severe infections, which we defined as an infection leading to hospitalisation or treatment with IV antibiotics, antivirals or antifungals. We saw statistically significant reductions in any infection requiring antimicrobial use and also these severe infections.
Beyond that, we just looked at the incidence of hypogammaglobulinemia and particularly in patients who had multiple immunoglobulin G measurements. What we saw was about 64% of patients with myeloma in this cohort had hypergammaglobulinemia. What we saw is that after the initiation of immunoglobulin replacement therapy fewer patients had hypergammaglobulinemia, this is not surprising. But, again, this would translate hopefully into a lower risk of infection within this vulnerable population.
To date this is the largest real-world cohort study of patients with myeloma treated with immunoglobulin replacement therapy. We believe that this study provides real-world insights into the patterns of immunoglobulin measurements, replacement therapy, and infectious outcomes in a particularly vulnerable population.
The takeaways are that it’s important to regularly assess immunoglobulin G levels and then IVIG, or immunoglobulin replacement therapy, can significantly reduce infections, infections requiring antimicrobials and the proportion of patients at risk.
