Developing Standard Operating Procedures for Using Bispecific Agents

Robert Mancini, PharmD, BCOP, FHOPA

BMT/Heme Pharmacy Program Coordinator

PGY2 Oncology Pharmacy Residency Director

St. Luke's Cancer Institute

Boise, ID

Targeted Oncology: How were standard operating procedures (SOPs) for bispecific T-cell engagers developed at your institution?

MANCINI: At our institution, I wrote all the protocols and I sent them to our physicians who signed off and made the changes that they wanted to see. I helped develop that base. As physicians, we have enough on our plates, but if you can have someone who helps develop those [SOPs] to at least give you a starting point, then you can weigh in on it, so that becomes a good option.

If you can find someone to…reach out to those institutions, and then help take that back and say, “What are we going to do with that?” That's one option. We also have a working group that developed this, sat down together, included all of those key stakeholders…to hash that out. But in the end, you're still going to have to have one person who is actually writing the protocols and initiating. If you're in the process, or you haven't yet started, it’s an important thing to consider who's going to be that one person that's going to write the protocol.

What was your experience at your institution setting up a bispecific administration program?

What happened was, we had our first patient and we flailed in the water. [We weren’t sure] what we were supposed to do with this patient. Luckily, the first patients were those receiving mosunetuzumab [Lunsumio]—patients who did not require inpatient administration. The risks and the tolerability were a little bit easier.

We knew how to manage cytokine release syndrome [CRS] and neurotoxicity. We have those pieces down. Now we need to think about where this patient can be treated with the mosunetuzumab. It does not require inpatient administration. We set that up, and we use EPIC, so we had to build our treatment plans and get that prepared for when the patient came in. Having gone through it with that first patient, we realized we need to formalize this process, because everyone's asking different questions [concerning] why we did this or that. The physician may see him with the first dose but an advanced practice provider may see him with the second dose and they don't necessarily know what the process is.

The [first] thing that we found that we needed was deciding how these patients are going to be selected. Is a patient a good patient for a bispecific agent? Is this a drug that requires inpatient vs outpatient administration? Is the patient capable of managing this? If not, do you need a caregiver? We developed caregiver requirements into our protocols…because what we found is the most important thing, especially if you're dealing with ICANS [immune effector cell–associated neurotoxicity syndrome] or neurotoxicity, is you can't rely on a patient knowing that they're having ICANS, or even some degrees of CRS.

We looked at how we are going to…determine what setting they're going to be treated in. Then, what are you requiring of the patients? This is a 2-way street. We as providers need to determine how we're going to treat these patients and give them those resources. But patients also have to take some of that responsibility on their own to have success with their treatment. What are those components they're going to require? And last, what are the caregiver requirements? Those are the pieces that we looked at in terms of how to develop [an SOP].

How do you initiate the first doses of a bispecific T-cell engager in your practice?

We are a larger community [cancer] center. We have our main site in Boise, Idaho, and then we have multiple clinics across Idaho. All of our patients will come to our primary site in Boise for initiation. They'll get referred to 1 of our bone marrow transplant/CAR [chimeric antigen receptor] T-cell therapy physicians who are familiar with this ramp-up toxicity profile, and then we have to decide if we going to keep them the whole time, or send them back. We face…issues with travel; our clinics are 2 and a half to 3 hours away, so are we going to make some of these patients drive up to 3 hours every week? At what point are we comfortable sending them back to that community institution?

If you look at the data for most of these products, once you get them through that first full treatment dose, or potentially the second full treatment dose, the risk of these toxicities drop off very rapidly and very extensively. [At the first doses], there is the risk. Then you get past that second treatment dose, and your risks are basically in the single-digit percentages for those acute, more difficult toxicities.

What we did is similar to a [patient receiving] CAR T-cell therapy or even an autologous [stem cell] transplant. We require them to get treated at the main institution site in Boise for the first month of therapy. Depending on the product, some of those are 4 doses if they're weekly, like teclistamab [Tecvayli], or 3 doses, if you're looking at one of the B-cell lymphoma products.