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ICML 2025 | Advice for managing the toxicities of ADCs, bispecifics & CAR T-cells in lymphoma
Stephen Ansell, MD, PhD, Mayo Clinic, Rochester, MN, discusses adverse events associated with antibody-drug conjugates (ADCs), bispecifics, and CAR T-cells used in the treatment of lymphoma. He highlights the need for providers to be aware of potential toxicities and explains that proactive steps should be taken to mitigate these risks, including prophylaxis and early intervention. This interview took place during the 18th International Conference on Malignant Lymphoma (18-ICML) in Lugano, Switzerland.
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Transcript
I think we’re very excited about novel therapies. As you mentioned, antibody-drug conjugates, which are bringing a payload directly to the tumor, and then immunotherapies that are activating the immune system to target the malignancy. The challenge we’re finding, and again not unexpected, is that those toxicities are directly proportional to the way in which the treatments work. So antibody-drug conjugates delivering a payload to the tumor, there are some slightly off-target or on-target but off-tumor effects which do end up causing side effects...
I think we’re very excited about novel therapies. As you mentioned, antibody-drug conjugates, which are bringing a payload directly to the tumor, and then immunotherapies that are activating the immune system to target the malignancy. The challenge we’re finding, and again not unexpected, is that those toxicities are directly proportional to the way in which the treatments work. So antibody-drug conjugates delivering a payload to the tumor, there are some slightly off-target or on-target but off-tumor effects which do end up causing side effects. And we see neuropathy, for example, with brentuximab vedotin, for example, as a significant challenge. When you’re looking at bispecific antibodies or CAR T-cell treatments, where you’re targeting the malignant B-cell, for example, we’re seeing really long-term depletion of antibody-producing cells. And so infections end up being a substantial challenge. So to the point of what can a provider do to anticipate that, firstly, know that it happens. Secondly, ask the patient about any side effects associated with that. But then most importantly, particularly in infections, prophylaxis is important and early intervention if patients get sick. All told, though, I think these therapies are reasonably well tolerated and outcomes are excellent. So the goal is really to use these drugs judiciously. And I think most providers are doing that.
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