Leo Gordon, MD: With standard chemotherapy, say R-CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone], it’s a worry mostly about neutropenia, fevers, and infection. And infection is high up on the on the list of things we see. Nausea [and] vomiting is better controlled now than it’s ever been. Neuropathy that we see from the vincristine in the in the CHOP regimen, we see [a] similar amount of neuropathy with polatuzumab in the pola-R-CHP [polatuzumab plus rituximab, cyclophosphamide, doxorubicin, and prednisone] regimen. Hair loss and fatigue are present. And then with any Adriamycin [doxorubicin]-containing regimen, there’s the risk of cardiac failure. We try to mitigate that by looking at echocardiograms before, and then I like to look at it in the middle of treatment. We don’t see it too often, and we only really see it when the dose of Adriamycin gets to a certain level.

Prednisone is part of all the regimens. So there’s bone loss that we probably don’t think about enough, that we should be replacing calcium and thinking about bone loss. We do worry a little bit about tumor lysis syndrome when starting chemotherapy. Honestly, I don’t see that too often in DLBCL unless the LDH is 1000 or 1500 U/L. So, I don’t worry too much about that when starting most patients with chemotherapy for DLBCL [diffuse large B-cell lymphoma]. The cellular therapies and I’ll speak about CAR T [chimeric antigen receptor T-cell therapy] first and then the bispecific therapies. The cellular therapy has a unique constellation of toxicities that I think takes some getting used to and understanding before we can routinely do it, which is why CAR T is not done everywhere. The hope is that bispecifics will be done everywhere. I don’t know. We’ll see. But [with] CAR T, there are 2 major toxicities that we see. One is the so-called cytokine release syndrome. It’s probably a result of the body’s response to the manipulated T cells that we’ve just given them. It’s mediated by interleukin 6 [IL-6] and similar to what happens when somebody has a bad infection and they get a fever, low blood pressure and manage mostly by IV [intravenous] fluids. We do have available a drug called tocilizumab, which is an IL-6 blocker. I’d say fluids is the first line of defense. The second line of defense is tocilizumab and then finally giving steroids. Dexamethasone often will help mitigate those. Then the other toxicities that that we worry about this. The first part is usually the first 4 or 5 days and then day 5 through about 8 we worry about neurologic toxicity, [which] can result anywhere from mild forgetfulness to encephalopathy and coma and seizures.

We don’t know what happens, what causes that. That’s unexplained. We just treat with steroids there. And there is some evidence that maybe using IL-1 blockers, a drug called anakinra, may help mitigate that. Those are the main cellular therapy toxicities with CARs. And I would say with the with bispecific antibodies, both are true again, but to a much lower extent, much less severe, much more manageable and manageable mostly as an outpatient, I would say, with the bispecific antibodies. These are unique toxicities. Long-term with the cellular therapies people have low immunoglobulin levels because we’re depleting B cells, which make immunoglobulin, and then we may see cytopenia [drop in white count and platelet count] that can last for several months or even 6, 8 months after CAR T[-cell] therapy. We don’t know why that happens. It’s probably an immune-mediated process, we think. So, those are those are the major toxicities: chemotherapy and then cellular therapy.

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