It’s been just over a year since the FDA approved the first engineered cell therapy for the treatment of certain patients with advanced synovial sarcoma, a rare cancer that affects fewer than 1000 Americans annually.

The treatment — afamitresgene autoleucel (Tecelra) — is a genetically modified autologous T-cell immunotherapy that targets the MAGE-A4 antigen in synovial sarcoma cells. It was approved under the agency’s accelerated approval pathway for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy treatment; are HLA-A02:01P, -A02:02P, -A2:03P, or -A2:06P positive; and who have a tumor expressing the MAGE-A4 antigen. The approval was based on the treatment’s efficacy in the phase 2, single-arm SPEARHEAD-1 trial, which showed an overall response rate of 39%.

The one-time infusion treatment is the first engineered cell therapy approved in a solid tumor and has the potential to dramatically change sarcoma treatment, which is typically treated with chemotherapy. However, the cell therapy comes with a significant cost — a list price of more than $700,000 — and is only available at specialized cancer centers.

Mihaela Druta, MD, a medical oncologist and vice chair of the Sarcoma Department at the Moffitt Cancer Center, Tampa, Florida, was a site principal investigator on SPEARHEAD-1 and has treated four patients outside of the trial setting since the FDA approval in August 2024. As in the trial, patient responses in the real world have been mixed. In an interview with Medscape Medical News, Druta explained how patients are selected, why certain patients achieve durable responses, and what oncologists should know about this new option.

Q: How do you select patients for this type of cellular treatment?

Druta: The first step is to test them for the HLA eligibility and if it is the right HLA, we can go and then test for the MAG4 antigen, which is typically consistently high and expressed. I often evaluate patients in the Sarcoma Clinic to see what prior lines of therapy they have had, their tumor burden, and the status of their disease. I also explain some of the logistics to make sure they understand the complexity of the process. Once we have the green light from this evaluation, we submit a request to the cellular therapy bone marrow transplant unit.

Q: What would cause you to exclude a patient from getting this therapy?

Druta: I’m not looking necessarily at the age of these patients, but I am looking mostly at the comorbidities. Patients who have high blood pressure, diabetes, a prior smoking history with COPD, and other comorbidities, they would not necessarily be the best candidates for these therapies. We also look at prior lines of therapy and the tumor burden. We know that with patients who have been through many lines of therapy, the quality of the T cells declines and they’re not very fit to have them modified and expanded prior to infusion. Also, the bigger the tumors are, the more we question if they are the best patients for this type of therapy.

Q: What are the potential safety concerns with this treatment?

Druta: Most of the patients in the trial developed Grade 1 or 2 cytokine release syndrome. When we treated them with supportive measures their symptoms resolved, and we’ve seen similar reactions in the real-world patients. Since approval, there have been some other side effects that were not seen on the trial, such as generalized rash. We did a biopsy on the patient who developed a rash and excluded other possible etiologies and concluded that the rash was possibly related to the therapy. Another patient experienced cough and shortness of breath that was possibly related to pneumonitis from the therapy. But this patient also had underlying COPD and was borderline in terms of being eligible for the therapy but had an amazing response. Overall, I have not seen huge differences between the trial experience for adverse events. We need to treat more patients to have a sense of what is happening in the real world.

Q: Is there research underway to better understand the real-world response?

Druta: I am in the process of establishing a consortium, starting with the other large sarcoma cancer centers in the US, including Memorial Sloan Kettering and Stanford. The idea would be to collect patient data and biospecimens, such as biopsies and the left-over T-cell product. This will allow us to understand not only how this therapy works in the real world but also why it works better in some patients than others and why it stops working in patients who initially have beautiful responses. Hopefully we will be able to collaborate to make this information available.

Q: Do you know why some patients stop responding to the therapy?

Druta: On the trial, having better and longer responses was associated with the persistence of the product in the peripheral blood. Not only was it persistent for a long time but also the product was maintaining this cytolytic or killing ability for more than 3 years after infusion. Looking at tumor biopsies that were conducted during the trial, we also learned that patients who responded to therapy had T cells that were successful in infiltrating the tumor microenvironment while among patients who didn’t respond, there was no trafficking of the modified cells in the tumor microenvironment. That is a very interesting finding that we need to explore.

Q: Are there significant hurdles for patients in accessing this new therapy?

Druta: We have been treating patients with sarcomas for more than 50 years with very heavy, cytotoxic chemotherapies that require patients to come weekly or every 3 weeks to the infusion center, dealing with all sorts of toxicities and missing work. To be able to have access to a completely different strategy and different mechanism to fight this disease, with just one infusion, is huge. From what I have seen, patients are extremely happy and motivated. Right now, the therapy is only available in large sarcoma centers and centers that are accredited to administer cellular therapies. In my opinion, this should be done in specialized centers, but we need to at least start testing patients for eligibility closer to home. In terms of cost, it can be very challenging for patients. This is definitely something that we need to work on and we have social workers who look for grants for patients. I’m also starting to work with patient advocacy groups and foundations on ways to ease some of that financial burden.

Q: What do oncologists need to know about this therapy as they see patients with synovial sarcoma?

Druta: Patients diagnosed with sarcoma, either synovial sarcoma or any other type of sarcoma, deserve to be evaluated in a multidisciplinary, tertiary cancer center where we have a team of pathologists, radiation oncologists, medical oncologists, surgical oncologists, and others who focus on sarcoma. Because of the rarity of this condition and the heterogeneity of the disease, we pretty much personalize the treatment of these patients. It’s also critical that these patients have the opportunity to be evaluated for participation in clinical trials.

The SPEARHEAD-1 trial was funded by Adaptimmune and correlative studies on Tecelra are sponsored by Adaptimmune and US WorldMeds. Druta reported having no relevant financial disclosures.