Preliminary findings from a phase I pilot study (NCT00398138) have demonstrated that the Wilms Tumor 1 (WT1) peptide vaccine (galinpepimut-S [GPS]) can be safely administered in Acute Myeloid Leukemia (AML) patients in Complete Remission (CR).1 Based on these findings, Peter G. Maslak, from the Memorial Sloan Kettering Cancer Center, New York, NY, and colleagues, conducted a phase II open-label study (NCT01266083), which is examining the safety and efficacy of GPS in AML patients in First CR (CR1). The results of the study were published in Blood Advances.2
In total, 22 WT1 positive AML patients in CR1 (median age = 64 years, [range 25–76 years]) were enrolled and treated in this study. Patients were administered six vaccinations subcutaneously biweekly over a 10-week period with the possibility of receiving six additional monthly doses if the patient remained in CR1. Of the 22 patients enrolled in this study, 14 (64%) completed more than six vaccinations and 10 (46%) received all 12 vaccine doses.
Additionally, Immune Responses (IRs) were also quantified after the 6th and 12th vaccinations using either CD4+ T-cell proliferation, CD8+ T-cell interferon gamma secretion (enzyme-linked immunospot), or the CD8-relevant WT1 peptide major histocompatibility complex tetramer assay.
- Relapse occurred in 15 (68%) patients during vaccination (n = 10), after the 12 doses of vaccination (n = 4) and after discontinuation of therapy (n = 1)
- Median Disease-Free Survival (DFS) from CR1 = 16.9 months
- Median Overall Survival (OS) from diagnosis: not reached but is poised to reach or exceed 67.6 months
- Median Event-Free Survival (EFS) from the time of first vaccination = 9.4 months
- Median OS from time of first vaccination = not reached
- There was no significant correlation found between baseline WT1 transcript levels and clinical outcomes
- IRs in evaluable patients (n = 14)
- Nine patients (64%) had IR in more than one assay, either CD4+ or CD8+
- Compared to non-responders (n = 5), median DFS (P = 0.11) and OS (P = 0.08) was longer in immunologic responders (n = 9)
- The most common toxicities included injection site reactions (46%), fatigue (32%), skin induration (32%), and injection site pruritus (27%)
- Two patients experienced hypersensitivity reactions that led to discontinuation
The results of this study demonstrated that GPS was safe, well-tolerated and stimulated immunologic responses in most patients with AML in CR1.
However, the authors highlighted that the therapeutic efficacy in this study should be interpreted with caution due to several reasons. Firstly, the patient group in this study were heterogeneous, and thus may skew the outcomes observed. Secondly, the group “may represent those with the best response” as they were in CR1. Lastly, patients who did not achieve IRs still had clinical response which might indicate that the assays used to determine IRs were not sensitive enough.
The authors further concluded that the results from this phase II study were superior to previously published outcomes for similar patient groups treated with conventional post-remission therapies. They further added that regarding the clinical efficacy, a larger randomized clinical trial is required with a more homogeneous patient cohort.