Dr Hans Lee Discusses Infection Mitigation Strategies for MM Treated With CAR T or Bispecific Antibodies

Patients with multiple myeloma (MM) who are being treated with bispecific antibodies or chimeric antigen receptor (CAR) T-cell therapies have an increased risk of infection that needs to be managed, explained Hans Lee, MD, associate professor and director of multiple myeloma clinical research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center.

In an interview with The American Journal of Managed Care^® (AJMC^®), Lee discussed what strategies are being used to mitigate that risk, including multidisciplinary collaboration.

Hans Lee, MD

Credit: The University of Texas MD Anderson Cancer Center

AJMC: What is the infection risk of bispecific antibodies for patients with MM relative to CAR T-cell therapies?

Lee: Both bispecific T-cell antibodies and CAR T-cell therapies are associated with increased infection risk. Although because CAR T-cell therapies are generally a one-and-done therapy, as far as right now, the infection period is a little bit more limited with CAR T-cell therapy, whereas the current paradigm for bispecific T-cell antibodies is to treat until disease progression. So, there is a lengthy duration of response to bispecific T-cell antibodies, which is a great thing. On the other hand, you see more exposure to these agents over a prolonged period of time and, hence, potentially more infection risk over a longer period of time when exposed to these drugs.

A really, really important area of research moving forward is: What's the optimal duration of therapy with these bispecific T-cell antibodies? And should we really treat until progression? I think there's a lot being looked at in terms of, for instance, fixed duration therapy or perhaps decreasing the frequency of the dosing to really limit the exposure to some of these agents and patients who already have a very deep response to their therapies.

AJMC: What are the existing strategies to mitigate infection risk in patients receiving bispecific therapies for relapsed/refractory (R/R) MM, and how effective are they at reducing infection rates?

Lee: So, there's a lot of research being done to try to mitigate the infection risk with bispecific T-cell antibodies. And I think we'll become a lot better at this in the next 3 to 5 years and more data are being gathered generated in this area. But for right now, the areas really involve infection screening, surveillance, and prophylaxis. For instance, our local institution screens for certain pathogens that might put patients at high risk for infections, things like hepatitis B, hepatitis C, and CMV [cytomegalovirus]. You know, we don't necessarily act on these tests if they're positive per se, but for us, if a patient is hepatitis B seropositive, we put them on hepatitis B prophylaxis. In terms of CMV, we do see quite a bit of asymptomatic CMV viremia. So, we don't necessarily act on and treat asymptomatic viremia, but we monitor CMV levels, and then if they get to a certain level, then potentially act on that as well.

Another aspect of infection mitigation strategy is prophylaxis, and so we definitely would recommend viral prophylaxis with valacyclovir or acyclovir. I think there's more emerging data on the risk of PJP [pneumocystis jiroveci pneumonia] with bispecific T-cell antibody treatment, so PJP prophylaxis is important. And finally, vaccination. So, we know that vaccination responses are probably still blunted in patients getting immunotherapy and MM, but vaccination is nevertheless very, very important. So, staying up to date on your influenza vaccine, pneumococcal vaccine, and COVID-19 vaccines are really, really imperative for our patients. This is going to be an evolving sort of area in the field. And we're just learning, about this and bispecific T-cell antibody therapies. And so, I think as more data are generated, these recommendations, these mitigation strategies will continue to evolve based on evidence.

AJMC: What are the gaps in our current knowledge and research surrounding infection risk and mitigation strategies in patients who have R/R MM?

Lee: Really, we don't really have much data still. And so, I think we need to generate data in a very systematic manner, really document infections consistently across different trials. I think we need to gather more data with the real-world studies,, and also prospective studies on ways we can mitigate infection risk. And I think really, through these studies, I think we'll get a lot more information on an evidence-based manner of how we can mitigate infections and how we can prophylax and how you screen and also conduct surveillance for high-risk pathogens. And finally, trying to determine the optimal duration of therapy, I think will be important in mitigating infection risk in the future; in patients who are already have a deep response to therapy, looking at decreasing the frequency of dosing as well as perhaps a fixed-duration therapy to really limit exposure to some of these agents and responding patients.

AJMC: How can multidisciplinary collaboration between hematologists, infectious disease specialists, and other health care professionals improve infection management in patients with R/R MM?

Lee: Multidisciplinary care in MM patients is so important. It's really, really important to collaborate with infectious disease physicians, especially managing our MM patients. And this is something we do at our local institution, and they're really a big part of the team. They know a lot about infectious disease, we know about myeloma, and really putting our minds together to best help our patients is so important for the best care for our patients.

We know that patients on bispecific T-cell antibody–based therapies can get hypogammaglobulinemia—basically a decrease in their IgG [immunoglobulin G] levels. And so, there's emerging data, for instance, that giving prophylactic IVIG [intravenous immunoglobulin], if the IgG levels are less than 400 mg/dL, could be beneficial in mitigating the risk for infection. So, this is another very, very important mitigation strategy for patients getting by bispecific T-cell antibody therapy.