Among high-risk patients with multiple myeloma, post-autologous stem cell transplantation (ASCT) immunization with the Wilms tumor 1 (WT1) peptide mixture galinpepimut-S (GPS) is well-tolerated and is associated with a “promising” progression-free survival (PFS), according to initial findings from a phase I/II open-label study presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago (abstract 8016).
“Administration of the novel WT1 heteroclitic peptide immunizer GPS in multiple myeloma patients post-ASCT demonstrates encouraging median PFS (currently 23.6 months), therapeutic response, and a favorable safety profile in this high-risk MM population with historically poor long-term outcomes,” reported Guenther Koehne, MD, PhD, and colleagues, at Memorial Sloan Kettering Cancer Center in New York. “This ‘off-the-shelf’ immunotherapeutic is easy to administer and has been specifically designed to elicit responses across most common HLA class I and II alleles.”
Nineteen patients were enrolled. Fifteen (79%) had high-risk cytogenetics at diagnosis.
Participants received the first dose of subcutaneous GPS immunization with Montanide adjuvant within 22 days of ASCT, followed by biweekly doses to a total of six doses. A booster dose was delivered every 4 weeks to a total of six booster doses. Granulocyte macrophage colony-stimulating factory was administered 2 days before and at each GPS dose. Lenalidomide (10 mg once daily) maintenance therapy was initiated 3 months after ASCT in all but one patient, who underwent bortezomib maintenance instead.
WT1-specific “CD8+ and CD4+ immune responses could be detected at various levels in all but two patients following GPS administration,” the authors reported. “These immune responses were induced not only against the heteroclitic peptides (within GPS), but also were detected against the corresponding native WT1 peptide sequences that are expressed on malignant plasma cells, as well as the ‘total pool’ of WT1-derived overlapping peptides.”
After a median follow-up of 18 months, the median overall survival in this population has not been reached. Overall survival and PFS rates were 88% (95% CI, 73–99) and 62% (95% CI, 42–92), respectively.
A phase II trial is being planned, they reported. It will “optimally integrate post-transplant immunotherapeutic strategies” with the goal of delaying relapse.
The study was funded by the Leo A. Guthart and Kathryn Medina Research Fund in Multiple Myeloma, and Sellas Life Sciences Group. One coauthor disclosed a consulting relationship with Sellas Life Sciences Group.