Pharmacists Play a Critical Role in Managing Risk and Maximizing Outcomes Before Cilta-Cel

As CARTITUDE-4 continues to clarify how pre–CAR-T disease control shapes both safety and efficacy, new insights emphasize the importance of pharmacist-led decision-making during the bridging period. In this second part of our Q&A, Binod Dhakal, MD, explains how response to bridging therapy should guide counseling on timing, supportive care, and regimen adjustments—and why proactive, multidisciplinary collaboration is essential to reduce cytopenias, prevent infections, and ensure patients reach cilta-cel infusion with the lowest possible disease burden.

Q: How should pharmacists interpret differences in prolonged cytopenia and fatal infection rates across response categories when counseling on timing of apheresis, lymphodepletion, or infusion?

Dhakal: The timing of apheresis and lymphodepletion doesn’t really change because you're trying to get the patient to CAR-T as soon as possible. The most important thing is what happens while they're waiting for CAR-T—that is key. You saw in the data that patients who progress while on bridging therapy ultimately tend to have worse outcomes from both a safety and efficacy standpoint.

So the bridging therapy chosen matters the most. Especially in the late-relapse setting, we did not used to have many good options because these patients had exhausted many drugs. But in the one-to-three prior line setting, patients can still be sensitive to most regimens. So it is important to choose a regimen the patient is not refractory to, that they can tolerate with minimal side effects.

And if patients do not respond to bridging therapy, there is still the opportunity to switch bridging regimens and try to get a response, because there is still a window before CAR-T. If they do not respond after one cycle, you can switch to another regimen. So counseling is important to look at disease tempo and burden.

It is also important to delay CAR-T infusion if the patient still has a high disease burden while on bridging, because you do not want to give CAR-T when disease burden is high or rapidly progressive—that cannot be changed after infusion, only before.

Patients often get T-cell collection and then return to the community setting while waiting for CAR-T to be ready. So close communication with the CAR-T center is essential, understanding disease characteristics and response to bridging, and giving additional therapy if needed.

Q: What considerations should pharmacists keep in mind when evaluating whether a patient with minimal response or progressive disease on bridging therapy might need adjustments or intensified supportive care before infusion?

Dhakal: If the patient has not responded to bridging therapy or has progression during bridging therapy and they are ready for CAR-T, it is important to take that into account. It is probably better to hold off on CAR-T infusion and change the bridging therapy.

In the late-relapse setting it is tricky because patients may not have many options. But in the CARTITUDE-4 population with one to three prior lines of therapy, patients have many options. Even in later lines, now with the use of bispecific antibodies—non-BCMA bispecifics like talquetamab—people are using those as bridging and getting very good responses.

So you have to consider the nature of disease progression, depth of response, underlying comorbidities, bone marrow reserve, infection risk, and how to monitor that during bridging. And if they are not responding, switching to a different therapy—either conventional regimens or even high-intensity chemotherapy—may be necessary, as long as you avoid interfering with T-cell collection.

These are important considerations before CAR-T infusion.

Q: Based on these findings, how might pharmacists collaborate with multidisciplinary teams to proactively address non-relapse mortality risks?

Dhakal: There are multiple ways. One, choosing the right bridging therapy and changing it if it doesn’t work. Another is ensuring patients receiving bridging therapy are well monitored for blood counts, receive enhanced infection prophylaxis, and get intravenous immunoglobulin support if needed.

The timing of lymphodepletion is critical—making sure it is done at an optimal time point along with the CAR-T infusion. Later, after CAR-T infusion, for patients at high risk of prolonged cytopenia or infection, being aggressive with prophylaxis and cytopenia management becomes critical, and pharmacy can help with that.

Escalation of bridging therapy—evaluating options based on prior refractoriness, exposure, and toxicity profile—is also a critical role for pharmacy, especially during the bridging period.

Q: Is there anything you want to add, or anything I didn’t think to ask?

Dhakal: The message of our study is very clear. Cilta-cel is a highly effective therapy. But of course, there are toxicities associated with cilta-cel and, in general, CAR-T. If you give CAR-T to a patient with very high disease burden and rapidly progressive disease, there is a likelihood of both acute and delayed toxicities.

So the strategy in the real world is how to debulk the disease effectively. That has been shown to be superior for safety and efficacy. Here in CARTITUDE-4, patients who achieved at least a partial response to bridging had superior outcomes with minimal toxicities, especially late toxicities.

This is a consistent message we are seeing across the board—that we want to debulk the disease and get this under control. In CARTITUDE-4’s one-to-three prior line population, the options for good bridging therapy to debulk the disease are much greater than in later lines.