Several immunotherapies known as immune checkpoint inhibitors are available today for patients with melanoma, as well as targeted therapies for patients with a BRAF or MEK gene mutation, but there are no effective treatments approved for patients with metastatic (spreading) or nonresectable (cannot be removed by surgery) melanoma whose disease progressed (got worse) after using an immune checkpoint inhibitor, or a BRAF or MEK inhibitor for those with gene mutations.
Recent results from a phase 2 clinical trial of patients with metastatic melanoma show the promise of lifileucel, an investigational immunotherapy known as adoptive cell transfer using T-cells called tumor-infiltrating lymphocytes, or TILs. The results were reported at the 2020 virtual American Society of Clinical Oncology annual meeting and showed that 1 infusion of this TIL immunotherapy led to responses in more than one-third (33%) of patients in the study.
All the patients had unresectable or metastatic melanoma whose disease progressed after receiving multiple immunotherapies, including PD-1 inhibitors such as Opdivo (nivolumab) or Keytruda (pembrolizumab) and the CTLA-4 inhibitor Yervoy (ipilimumab), and/or targeted therapies with BRAF or MEK inhibitors.
The long-term results showed a reduction in disease burden in 81% of patients who received this TIL immunotherapy, including patients whose disease was refractory (not responding) to PD-1 inhibitors.
“Lifileucel therapy can result in responses for those who have metastatic melanoma that is primarily refractory to PD-1 antibody therapy,” said lead investigator Amod Sarnaik, MD, Surgical Oncologist, Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center in Tampa, Florida.
Improved Long-Term Results
The study included 66 patients with unresectable or metastatic melanoma whose disease progressed after treatment with at least 1 immunotherapy, including a PD-1 inhibitor, and for those with a BRAF V600 mutation, a BRAF inhibitor or the combination of a BRAF and a MEK inhibitor Braftovi and Mektovi (encorafenib and binimetinib).
The patients were divided into 2 groups; those in group 2 had received an average of 3 or more previous therapies, including immunotherapy with a PD-1 inhibitor and 80% of them received immunotherapy with a CTLA-4 inhibitor.
Of the 17 patients with a BRAF V600 mutation, 15 had previously received the BRAF and MEK inhibitor targeted therapy. More than two-thirds (77%) of the patients had metastatic melanoma, and 42% of patients had melanoma that spread to the liver and/or the brain.
In group 2, the response rate to TIL immunotherapy was 36.4%, including 2 patients with complete responses (no sign of cancer) and 22 (33.3%) with partial responses. An additional 43.9% of the patients had stable disease.
After an average follow-up of 18.7 months, the average length of response was still not reached, meaning patients are still responding to treatment. Long-term responses were demonstrated regardless of patients’ age, type of previous immunotherapy or targeted therapy, and whether they had a BRAF mutation or not. The responses were equal in patients with high and low PD-L1 expression.
In all, 79% of the patients whose cancer got better with TIL therapy had previously received immunotherapy with the CTLA-4 inhibitor ipilimumab, which is approved for patients with unresectable or metastatic melanoma.
“Overall, these data indicate that responses from lifileucel therapy are achievable for subjects across a relatively broad range of clinical and pathologic features,” said Dr. Sarnaik.
The responses to therapy improved over time, he emphasized, and 16 patients had responses lasting more than 1 year.
“In general, the adverse events were typically expected for a treatment regimen that includes non-myeloablative lymphodepleting chemotherapy and infusional bolus interleukin-2,” said Dr. Sarnaik.
The serious side effects (grade 3 or 4) included thrombocytopenia in 81.8% of patients, anemia (56.1%), and febrile neutropenia (54.5%).
The time to having side effects usually started relatively soon after receiving the infusion with lifileucel therapy, which resulted “with a paucity of new adverse events that start beyond 14 days of TIL infusion,” Dr. Sarnaik added.
- The immunotherapy lifileucel uses T-cells called tumor-infiltrating lymphocytes, or TIL, for the treatment of melanoma
- In a clinical trial of patients with metastatic melanoma, 33% of the patients had a response to treatment after only 1 infusion of TIL therapy
- This included 2 patients who had a complete response to this treatment, 22 patients who had a partial response, and almost half (43.9%) of the patients had stable disease
- Patients who received lifileucel had an 81% reduction in disease burden, including patients whose melanoma did not respond to therapy with a PD-1 inhibitor
- After an average of 18.7 months, patients were still responding to treatment, regardless of their age, previous treatment they received, and BRAF mutation status
- The safety of lifileucel was as expected, with thrombocytopenia as the primary side effect