Serial vaccination with galinpepimut-S induces immunologic responses in patients with acute myeloid leukemia (AML) who are in remission. Disease-free survival (DFS) and overall survival (OS) improved in patients with AML who had an immune response to galinpepimut-S, according to data from a phase 2 trial of galinpepimut-S that were presented at ASCO 2016.
AML has long been recognized as an immunoresponsive disease in the transplant setting. “Many investigators have attempted to recapitulate this well-described immunologic effect outside the transplant setting using a variety of approaches,” said lead investigator Peter George Maslak, MD, Chief of the Hematology Laboratory Service, Memorial Sloan Kettering Cancer Center, New York, NY. “To that end, our group…has focused on a vaccine-based approach targeting the WT1 antigen.”
He explained why the WT1 antigen is a relevant immunologic target. The WT1 gene is a transcription factor with limited expression in normal tissue. It is overexpressed in myeloid malignancies, including in AML. WT1 is found in early leukemia progenitors and possibly in leukemic stem cells. In addition, the expression of WT1 is a prognostic marker and an indicator of minimal residual disease in AML and in myelodysplastic syndrome. It is processed and presented to the immune system as evidenced by the ability to detect WT1-specific cytotoxic T-lymphocytes in patients with AML and chronic lymphocytic leukemia who are in remission.
Heteroclitic analog WT1 peptides can induce a reactive T-cell response to native peptides, and peptide vaccines derived from WT1 can induce cytotoxic T-lymphocyte recognition and the killing of WT1-expressing leukemia cell lines.
Galinpepimut-S Is Safe and Effective
The vaccine consists of 2 native and 2 heteroclitic WT1 peptides designed to activate CD4+ and/or CD8+ T-cells. Galinpepimut-S has been proven to be safe and immunogenic, and has prolonged survival in patients with AML.
The study included 22 patients with AML who completed chemotherapy and were in remission by standard response criteria. The patients received 6 vaccinations administered with granulocyte-macrophage colony-stimulating factor in Montanide ISA-51 adjuvant over 10 weeks, with the potential to receive 6 additional monthly doses if the disease progressed after assessment at 12 weeks.
The prognostic risk was favorable in 8 patients, intermediate-1 in 7 patients, intermediate-2 in 3, adverse in 3, and undetermined in 1 patient. In all, 95% of the patients received a standard induction regimen of cytarabine plus anthracycline.
Overall, 64% of the patients completed 6 vaccinations, and 45% completed all 12 vaccine doses. A total of 15 patients in the study relapsed: 10 had relapsed disease while receiving galinpepimut-S, and 10 patients died (9 from disease progression). The median DFS for the entire group was 23.75 months.
Overall, 12 patients are still alive, 9 of whom are in first complete remission, and 3 after stem-cell transplant. The median OS for the entire group was 62.5 months.
The most common adverse event was local skin irritation, which included 45.5% of patients with a grade 1 or 2 injection-site reaction and 31.8% with grade 1 or 2 skin induration. Transient decreases in white blood cell count (27.3%) and platelet counts (18.2%) were also observed, none of which resulted in a transfusion or hospitalization. Two patients discontinued therapy because of probable hypersensitivity reactions.
Immunologic correlative data were available for 14 of the 22 patients: 4 of 9 patients had a CD4+ response, and CD4+ responses were seen across human leukocyte antigen (HLA) class II subtypes. Of 7 patients, 6 had a CD8+ response, and specific CD8+ responses were observed in patients with HLA-A0201.
“There was a trend toward improved outcome with the immune responders, although this is not significant,” said Dr Maslak. The median DFS was 15 months in the 5 patients with a negative immune response and had not yet been reached in the 9 patients with an immune response. Similarly, the median OS was 50.5 months in patients who had a negative immunologic response and had not yet been reached in patients with a positive immunologic response.
“Ultimately, clinical efficacy will need to be determined in the context of a large randomized study,” Dr Maslak said.