How Pharmacists Can Navigate Key Differences and Toxicities of Emerging Bispecific Antibodies in R/R DLBCL

As bispecific antibodies rapidly expand into treatment pathways for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), pharmacists are taking a central role in guiding agent selection and managing increasingly complex toxicity profiles. In this interview at the Hematology/Oncology Pharmacy Association 2026 Annual Conference, Matthew Warrick, PharmD, BCPS, BCOP, breaks down the subtle mechanistic differences among agents such as epcoritamab, glofitamab, and mosunetuzumab, and explains how dosing logistics, cytokine release syndrome (CRS) risk, neurotoxicity concerns, and infection prophylaxis strategies shape real-world decision-making as these therapies move into combination regimens.

Q: Several bispecific antibodies are now available or in development for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). From a pharmacist’s perspective, what are the key mechanistic or pharmacological differences between agents like epcoritamab, glofitamab, and mosunetuzumab that might influence agent selection for a given patient?

Matthew Warrick, PharmD, BCPS, BCOP: So I think the first thing to consider is that mechanistically, they are going to be very similar between all 3 agents, and by 3 agents, I’m specifically talking about glofitamab (Columvi; Genentech), epcoritamab (Epkinly; AbbVie, Genmab), and mosunetuzumab (Lunsumio; Genentech).

The biggest thing to think about, as far as main mechanistic differences, is their binding sites. With epcoritamab, its binding epitope is similar to that of ofatumumab (Kesimpta; Novartis), so it is actually slightly at a different CD20 site than the other bispecifics. That allows epcoritamab to be combined with other CD20 monoclonal antibodies, such as rituximab (Rituxan; Genentech, Biogen) or something else. So that is one reason why you will see it in combination with another CD20 antibody, which can be confusing when you first see it. That is one unique difference.

Glofitamab has a similar binding site to that of obinutuzumab (Gazyva; Genentech). It is also unique in that it has this 2:1 CD20 to CD3 T-cell structure, so it can actually bind to 2 CD20-positive B cells for every 1 CD3-positive T cell. Lastly, mosunetuzumab has a similar binding site to rituximab. That being said, they all still behave the same way, but there are a few unique differences from that point of view.

The other main differences, when it comes to selecting between them, involve ramp-up dosing and how frequently those doses are escalated, as well as the onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). That is something to think about in terms of selecting these agents and how often patients are able to come to the clinic.

Regarding the onset of CRS—specifically with glofitamab and epcoritamab—it is recommended to hospitalize patients after the doses associated with the highest CRS risk: after the first dose of glofitamab and after the third dose of epcoritamab. That requirement is not there for mosunetuzumab, so that agent can be given completely outpatient if appropriate.

Also, since mosunetuzumab—specifically in combination with chemotherapy or technically immunotherapy with polatuzumab vedotin (Polivy; Genentech)—has less risk of some of those adverse effects than what we see with the other bispecific-combination regimens, particularly CRS and ICANS, you do not have to admit those patients. So in patients where you are concerned that they would not be able to tolerate some of the traditional chemotherapy used in combination with the other 2 agents, using a completely immunotherapy-based regimen, like mosunetuzumab and polatuzumab, could be advantageous.

Q: As bispecific antibodies move into combination with salvage chemotherapy or immunotherapy regimens, how should pharmacists approach the added complexity of overlapping toxicity profiles compared to traditional chemoimmunotherapy backbones?

Warrick: I think the first thing for us to discuss is the elephant in the room of CRS and ICANS. That is something institutions will hopefully have a protocol for—or at least can start planning to have a protocol for—not only for our lymphoma-based CD20 × CD3 bispecific antibodies, but also if institutions are trying to utilize bispecifics in the myeloma space or in some of our solid tumor spaces. I think it is very important for institutions to have a standardized protocol for how we treat CRS and ICANS, and as pharmacists, we need to be very involved in building those protocols.

If we are comfortable with how we treat and monitor CRS and ICANS, that should not be too much of a concern when we use bispecifics in combination with chemotherapy. Interestingly, I do not know that we can say this with absolute certainty, but I think there are data showing that when we use bispecifics as monotherapy, there is a higher risk of CRS and ICANS than when we use them in combination with chemotherapy or immunotherapy. So there could actually be some benefit to using bispecifics in combination—maybe some debulking with chemotherapy and a reduced risk of CRS and ICANS. That should hopefully make providers feel comfortable using these combinations. If they are already comfortable using the monotherapies in the third-line or later setting, knowing that you can use these earlier in combination—with potentially less CRS and ICANS risk—should be reassuring.

Another toxicity to think about is infection risk. Since we are now combining bispecifics with chemotherapy, we get some of those more traditional side effects, and there may be additive or synergistic effects. So we see increased infection risk with bispecific combinations compared to regimens like gemcitabine-oxaliplatin (GemOx), or regimens similar to that. It is important for us to monitor closely for infections.

Given that GemOx is considered an intermediate-risk regimen for febrile neutropenia, you do not technically have to give growth factor, but for example, in the STARGLO trial (NCT04408638) with glofitamab plus GemOx, all patients were required to receive growth factors. I think that is a great supportive-care step we can take upfront for all these patients—making sure we give growth-factor support to reduce infection risk and reduce the depth of the neutropenic nadir.

For other infection prophylaxis, we should keep a close eye on counts so we can add bacterial or fungal prophylaxis if they have extended periods of neutropenia. At our institution, we add Pneumocystis jirovecii pneumonia (PJP) prophylaxis to all patients receiving bispecifics, so that is another additive consideration.

Lastly, something not talked about a lot is peripheral neuropathy rates. With oxaliplatin—being a platinum agent—the hot and cold sensitivities and neuropathies are not necessarily reversible like they are with other chemotherapies. We have seen a trend toward higher neuropathy rates in bispecific-chemo combinations compared to standard chemoimmunotherapy combinations like GemOx.

It is important for us to monitor those toxicities closely. Again, there are no data to support this as a practice change, but with oxaliplatin specifically, if you think about how we use it in regimens like FOLFOX for gastrointestinal cancers, we can potentially drop that drug after 3 or 4 cycles because of adverse effects and still retain efficacy. I am not saying we can do that here—we do not have the data—but I think it is something to consider: if patients are having adequate responses to the bispecific-chemotherapy combination and they are receiving oxaliplatin, is that something we could dose-reduce or even drop in future cycles after a complete response to help spare toxicity?

I will say that with mosunetuzumab and polatuzumab, since that combination does not include oxaliplatin, there is a much lower risk of peripheral neuropathy. That might be a potential benefit of that regimen.