Late-Line Use of TILs in Melanoma Leaves Few Bridging Options

Tumor-infiltrating lymphocyte (TIL) therapy is an expanding option in patients with recurrent advanced melanoma. However, the logistics of manufacturing the adoptive cell therapy from a patient’s tumor cells and the makeup of the eligible patient population present obstacles to TIL access. During a live Case-Based Roundtable event in Cleveland, Ohio, Daniel Olson, MD, assistant professor of medicine at UChicago Medicine, and participating oncologists discussed the barriers to treatment, especially when it comes to referring patients to tertiary care centers that are far from the patient’s home. Additionally, they discussed what bridging options could be used while patients await TIL administration, considering that most patients at this point have disease that is refractory to all efficacious treatments.

Register today to join a Case-Based Roundtable near you.

DISCUSSION QUESTIONS

• What factors contribute to hesitation or delay in referring patients for TILs?​
• How do you decide what bridging therapy to give while the patient is being evaluated for TILs?

Seema Misbah, MD: I have a patient who is taking care of her 90-year-old mother. Neither of them drive and it is a [challenging] social situation.

Daniel Olson, MD: Got it. Sure, that makes sense.

Aneel Chowdhary, MD: In general, in the urban areas, you have larger university centers, and you have larger melanoma programs. They are going to have easy access. But if you go out into smaller, medium-sized towns where you don’t have that, [we have] these social issues and transportation issues. I think that’s where you’re going to have more hesitancy, how to get patients, how to make contact, get the patients to the right team and have them on board.

Olson: I agree. It is a challenge, and some of you] may have more experience with referring patients for chimeric antigen receptor T-cell therapy in patients with lymphoma and leukemia. That is something you have to consider, because they just have to be [close to] the treating center for a certain period of time to get them through the cytokine release syndrome period. It’s kind of similar with TIL. You need to be around the center. There are ways to support the patients that come through the sponsor, whether you can actually cover their hotel stay and things like that, so they can come and stay, but that still has to be a certain type of patient who’s willing to do that. It’s not everybody. That’s a big ask for people, especially if they’re not familiar with the city where they’re going to be.

How do you decide what bridging therapy to give patients? Have you coordinated with the treating site about how to keep patients under control, either waiting for their manufacturing or anything like that?

Neha Mitra, MD: I haven’t done it, but usually when we refer, they tell us exactly what to do.

Olson: Got it, soyou take their feedback on it too.

Chowdhary: If someone who has progression beyond a couple lines of therapy, sometimes there isn’t much to bridge with. I have a patient [who] I’ve been treating for many years. He [underwent assessment] for TILs, they were extracted and everything. But then he went into severe respiratory failure, got a pulmonary embolism…a couple months ago…as we were talking to the [TIL] team at the main campus, everything was ready and getting started, but there wasn’t anything we could do for bridging therapy. He had exhausted all options, and he’d been on 1 trial as well. This was going to be a fourth line; he was BRAF wild-type, so I don’t even know what bridging therapy you can use when you’ve exhausted everything.

Olson: Yes, it’s an unsettled question. I totally agree. I think I’ve treated 35 patients at this point, and I’ve coordinated with patients from very far away, and it’s been a challenge that sometimes, when TIL therapy is the last good option for a patient and you want to do everything to be able to offer it to them, if you don’t have targeted therapy, if you’ve gone through immunotherapy, the only real options would be chemotherapy, which, in general, doesn’t work that well for melanoma. But there are some data, back before checkpoint inhibitors, there was a trial of carboplatin/paclitaxel, sorafenib vs carboplatin/paclitaxel, and the response rate was [approximately] 25%.¹ I’ve definitely given carboplatin/paclitaxel in melanoma and had reasonable response rates.

So, I’ve done that in a pinch for some patients, or if some patient comes in and I’m a little worried about their performance status and the pace of the melanoma, sometimes I’ve said, let’s see if we can get this under control with carboplatin/paclitaxel or even dacarbazine and tried that for a couple cycles. It’s worked for some patients. It doesn’t work for everyone. Clearly, if someone’s coming to you with that level of disease, it’s a high-risk patient, and you don’t know if it’s going to work, but that’s been one thing I’ve tried.

There’s also a small study of lenvatinib [Lenvima] and pembrolizumab [Keytruda], which was used for patients with melanoma after PD-1 and had a 30% response rate.² I had never really used it, and I started to try and use it as a bridging therapy, not knowing how toxic lenvatinib was. I started at the full dose, and I would never do that again.

Misbah: I saw it in an NCCN overview and I was surprised. I know it’s used a lot in kidney cancer, but not in melanoma.

Olson: You would probably never start at the full dose. You’d probably start low and start low and go slow and go up, but it does have a reasonable response rate. That’s another bridging therapy that some people would consider.

Misbah: [Regarding] the transportation issue, what I think really helps is telemedicine counseling. It sometimes involves family members. I have been having that, especially with CAR T, just making sure that the team—they can convince them [to be treated]. I had a couple [patients] and [the CAR T physician] convinced them. I see that that technology is helping right now; before we didn’t have it.

Olson: I hope it stays around. …I use it all the time, and since I’ve started doing TIL I’ve actually gotten licenses in Wisconsin, Michigan, and Indiana, because I have patients who come from far away, and there is typically a 5-week manufacturing period after surgery, where they’re back with their home team and they’re checking in with their home team, but I don’t always know what’s going on, and the ability to have a check-in to know what’s going on makes a huge difference. I like to use that. It makes the whole process a lot easier, basically, just keeping an eye on things [given that] it’s such a unique therapy.

Joseph Attallah, MD: What’s your opinion of temozolomide [Temodar] or nab-paclitaxel for bridging?

Daniel Olson, MD: I think temozolomide is just like dacarbazine; it has modest activity, and you can certainly try that. You might try that over dacarbazine if they’ve got brain metastases; we know the central nervous system penetration is a little bit better. I think temozolomide is totally reasonable. I haven’t used nab-paclitaxel much, but I know there are the data from carboplatin/paclitaxel that it can work, so I think it’s reasonable. I think more conventionally in melanoma, it’s carboplatin/paclitaxel. We have better data on it, the same with dacarbazine, but none of them are home runs. It’s something we can try.

Attallah: There’s no right or wrong answer for bridging therapy.

Olson: No, there is no right or wrong answer. You see what you think will work best and what they will tolerate.

Register today to join a Case-Based Roundtable near you.

_{DISCLOSURES: Olson previously reported consulting fees from Iovance, Obsidian, Novartis, and Aadi.}

REFERENCES

1.Flaherty KT, Lee SJ, Zhao F, et al. Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. J Clin Oncol. 2013;31(3):373-379. doi:10.1200/JCO.2012.42.1529

2. Arance A, de la Cruz-Merino L, Petrella TM, et al. Phase II LEAP-004 study of lenvatinib plus pembrolizumab for melanoma with confirmed progression on a programmed cell death protein-1 or programmed death ligand 1 inhibitor given as monotherapy or in combination. J Clin Oncol. 2023;41(1):75-85. doi:10.1200/JCO.22.00221