Nov 7, 2026 · @Sajeve thomas
Why I spent my weekend in Phoenix
SITC is the meeting where the future of immunotherapy gets previewed, sometimes years before it reaches a community infusion chair. This year’s 41st Annual Meeting brought nearly 1,200 abstracts to the Phoenix Convention Center. I focused on the Friday and Saturday sessions, with one question in mind: what will change for my patients, and for yours?
I’ll be honest about one thing up front. A good share of SITC is deep basic science, and some of it goes over my head. Single-cell atlases and spatial transcriptomics are where tomorrow’s drugs come from, but they aren’t always easy to translate on a Monday morning in clinic.
So this post is a filter. These are the abstracts in melanoma and sarcoma that I think matter most to community oncologists, referring physicians and our healthcare partners. I’ve also included a few ideas from the hallways that made me rethink some very ordinary things, like what time of day we hang the bag or what food/drug affect the gut microbiome.
Melanoma 1: TIL therapy without the IL-2 problem
Amsokigene autoleucel (amsoki-cel, formerly OBX-115) in checkpoint-resistant advanced melanoma. Presented by Dr. Rodabe Amaria, MD Anderson Cancer Center.
If you’ve referred a patient for TIL therapy, you know the hardest part usually isn’t the cells. It’s the high-dose IL-2 that follows. IL-2 is what makes TIL feel like an ICU-level commitment, and it’s why many fit patients are still turned away.
Amsoki-cel is engineered with membrane-bound IL-15, so the cells carry their own growth signal and don’t need high-dose IL-2 support. Dr. Amaria presented updated results from the phase 1/2 Agni-01 study:
- 67% response rate at the recommended dose (10 of 15 patients), including 2 complete responses
- Median progression-free survival of 8.3 months, and median duration of response not yet reached at 14.3 months of follow-up
- A third of patients still responding at 12 months after a single infusion
- A hard-to-treat population: 93% had already received ipilimumab plus nivolumab
The numbers are early and the cohort is small. But the direction is exactly what our field needs: TIL that more patients can safely get through. The data were also published in Nature Medicine the week of the meeting.
Now enrolling in Orlando
I wasn’t an investigator on the data presented in Phoenix. But we’ve just opened an amsoki-cel study at AdventHealth, and we’re now enrolling:
- Advanced melanoma that has progressed on checkpoint inhibitors with no more than two lines of previous therapy, as well as first-line metastatic melanoma, even if the patient has already started one or two cycles of PD-1-based therapy can still enroll!
- Non-small cell lung cancer that has progressed after prior therapy
If you’re caring for a patient who fits, please reach out to me directly at sajeve.thomas.md@adventhealth.com. TIL therapy works best when we see patients early, before they’ve lost the reserve to get through it. A quick call now is far better than a referral after the next progression.
Melanoma 2: two bispecifics, one eye cancer
Brenetafusp plus tebentafusp (KIMMTRAK) in first-line metastatic uveal melanoma. Late-breaking oral presented by Dr. Omid Hamid, The Angeles Clinic and Research Institute, a Cedars-Sinai affiliate.
Uveal melanoma behaves nothing like its cutaneous cousin, and checkpoint inhibitors do little for it. Tebentafusp changed that. It was the first drug to improve survival in this disease, and its five-year data this spring showed it doubled the chance of being alive at five years.
The new idea is to pair two T-cell engagers that hit two different targets on the same tumor. Tebentafusp targets gp100. Brenetafusp targets PRAME, a protein that many melanomas and other cancers overexpress. Both require HLA-A*02:01, so the same blood test selects patients for either drug.
In 17 evaluable patients treated first-line with the combination:
- 29% response rate, with a median duration of response of about 24 months
- 71% disease control rate
- An estimated 70% alive at two years
- Deep ctDNA molecular responses, which I found the most telling result of all
That last point deserves a sentence for community colleagues. With tebentafusp, CT scans often understate benefit, and a falling ctDNA level has tracked with survival better than RECIST shrinkage. Seeing strong molecular responses with the combination suggests the signal is real, even in a small phase 1. A randomized phase 2/3 trial, DUET-UVEAL, will now test the combination against tebentafusp alone.
The implications reach beyond the eye. PRAME is expressed in most cutaneous melanomas too, which is why brenetafusp is being tested first-line in stage IV cutaneous melanoma with nivolumab-based therapy (the PRISM-MEL-301 trial). We’re opening that study at AdventHealth now. Pair it with our liver-directed HEPZATO program for uveal melanoma, and Central Florida patients have more options than ever close to home.
Sarcoma: cell therapy is arriving, with fine print
TIL for UPS and dedifferentiated liposarcoma
Lifileucel in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS). Oral presentation by Dr. Lauren Banks, Memorial Sloan Kettering Cancer Center.
Dr. Banks presented clinical and translational follow-up from MSK’s pilot study of lifileucel, the same TIL product we use for melanoma. In the first 8 evaluable patients who received in-spec product, half had a confirmed response, split evenly between the two subtypes. All four responses were still ongoing at data cutoff. The FDA has granted Fast Track, and a registrational trial, SARATOGA, is enrolling.
I wasn’t surprised by the responses. UPS in particular is one of the more immune-active sarcomas. What I am watching is lymphodepletion toxicity.
In melanoma, most TIL patients have never had chemotherapy. Their bone marrow arrives fresh. Sarcoma patients usually arrive after one or two lines of doxorubicin- or ifosfamide-based chemo, and then we ask that same marrow to absorb cyclophosphamide and fludarabine. In this study, all 10 infused patients had grade 4 cytopenias. They resolved, but that’s a real cost. Patient selection and timing of referral will matter as much as the cells themselves.
Engineered T cells in synovial sarcoma
Afamitresgene autoleucel (afami-cel, TECELRA) and the SPEARHEAD-1 experience. Presented by Dr. Sandra D’Angelo, Memorial Sloan Kettering Cancer Center, lead author of the SPEARHEAD-1 trial.
Afami-cel was the first engineered T-cell therapy approved for any solid tumor, and it received full FDA approval this June for patients 12 and older with MAGE-A4-positive synovial sarcoma. Dr. D’Angelo’s main point was clear, and it echoes the original SPEARHEAD-1 analysis: patients do best when they have higher MAGE-A4 expression and lower-volume disease.
The practical lesson for referring oncologists: test early. HLA typing and MAGE-A4 testing take time, and manufacturing takes about six weeks. The best afami-cel candidate is the synovial sarcoma patient whose disease is still manageable, not the patient in their last good month.
On a personal note, Phoenix gave me the chance to connect with the team at US WorldMeds, which now owns TECELRA. I’m hopeful about bringing this option to Central Florida patients. More to share when I can.
Three ideas that made me rethink the ordinary
Hot, excluded, and why the difference matters
One of the keynote discussions walked through resistance through the lens of where T cells sit in the tumor. In an inflamed tumor, T cells are inside it but worn out. In an excluded tumor, T cells are lined up at the border and can’t get in. The two look similar on a pathology report that just says “PD-L1 positive,” yet they likely need different fixes. Exhausted T cells may need a second checkpoint or fresh cells, as with TIL. Excluded T cells may need something that breaks down the barrier first for example targeting TGF-beta which seems to be implicated. I expect this kind of classification to show up in trial eligibility within a few years.
Fed or fasting?
Another session explored data suggesting that a patient’s metabolic state around infusion may change how the immune system responds to checkpoint blockade. In the setting discussed, that meant patients who ate late the evening before treatment versus those who fasted. This is early, and it’s being studied prospectively, so I’m not changing any instructions yet. But it’s a reminder that the patient’s body around the IO drug is part of the treatment.
Morning or afternoon?
The timing of the checkpoint infusion itself came up too, in a lively probably the best pro/con debate I’ve seen. The presenters really dogged each other! Our immune system runs on a circadian clock, and a growing number of studies link earlier-in-the-day infusions with better outcomes. That includes melanoma data showing worse survival when more of the infusions were given in the afternoon, and a small randomized trial in lung cancer. The evidence is still debated and prospective trials are underway.
If it holds up, it may be the cheapest intervention in all of oncology. It would cost one scheduling change. Infusion center managers, take note.
The side effect nobody would order
The most memorable abstract for me was a rare toxicity case report: acquired generalized lipodystrophy after checkpoint therapy. The patient’s immune system attacked his fat cells. He lost his subcutaneous fat almost everywhere and looked lean and sharply muscular. After immunosuppression, repeat imaging showed the fat layer coming back.
This is a serious event, not a cosmetic one. Lipodystrophy can cause severe insulin resistance, very high triglycerides and fatty liver. In several published cases, steroids did not reverse it, which makes this recovery notable. If a patient on immunotherapy loses weight quickly with new diabetes or a jump in triglycerides, think of it.
Still, the irony wasn’t lost on anyone. In a world where everyone is on a medication to lose weight, here was a patient whose immune system did it for free, and we had to stop it. Afterward, a few colleagues joked about finding the T-cell clone that kills fat cells and taking it to market. Nobody’s filing that patent. But it’s a good reminder of how powerful, and how indiscriminate, a fully unleashed immune system can be.
Bringing it home
The theme I keep coming back to is cell therapy for solid tumors. It isn’t one product anymore. It’s a toolbox: TIL, engineered T cells and bispecifics that make the patient’s own T cells do the work. Each comes with its own logistics, its own toxicities and its own best window of referral.
That last part is where community oncologists matter most. The patients who do best with these therapies are usually identified early, tested early and referred while they still have reserve. Our job at an academic cell therapy program is to make that handoff easy, and to send patients back to their home oncologist for everything they can get closer to home.
I left Phoenix with a full notebook, a few new collaborators and a better sense of what’s coming to Central Florida next. Better than yesterday. On to the next one.
Disclosure: Dr. Thomas is a principal investigator on cellular therapy and immunotherapy trials in melanoma. All data cited are drawn from public conference presentation and published reports.
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.
Disclosures:
Dr. Thomas serves as a speaker for BMS, Merck, Ipsen, Natera, Immunocore, Pfizer, Sun Pharma, SpringWorks. He also receives industry grants in support of numerous clinical trials.
Patient cases described in this post are composites and have been altered — including but not limited to diagnosis specifics, demographics, timeline, and clinical details — to protect patient privacy and confidentiality. No case represents an actual, identifiable patient, and any resemblance to a specific individual is coincidental. Clinical scenarios involving other providers have similarly been altered and are presented for educational purposes only, not as a representation of any specific person’s practice. This post is for general educational purposes and does not constitute medical advice; it should not be used to guide individual treatment decisions. This article is for education and general information only. It is written about an anonymized case, shared with permission, and it is not personal medical advice. The individual described is not a patient of the author, is not treated in the United States or at the author’s institution, and no doctor–patient relationship is created by reading this. Statistics and treatment options are summarized from the current oncology literature and evolve quickly.
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