Investigating a WT1 Peptide Vaccine in Patients With Acute Myeloid Leukemia

In an open-label, phase II study, treatment with galinpepimut-S (GPS) – a vaccine targeting the Wilms tumor 1 (WT1) protein – was well tolerated in adults with acute myeloid leukemia (AML) whose disease was in first complete remission (CR1). The results were published in Blood Advances.

“A National Cancer Institute consensus study on prioritization of cancer antigens ranked the [WT1] protein as the top immunotherapy target in cancer,” wrote lead author Peter G. Maslak, MD, chief of the Hematology Laboratory Service at Memorial Sloan Kettering Cancer Center in New York, and colleagues. “[Our results] support the continued investigation of WT1 vaccination as a strategy for AML post-remission therapy.”

The trial included 22 patients (median age = 64 years; range = 25-76 years) with a histologic confirmation of WT1-positive AML who were treated at Memorial Sloan Kettering Cancer Center. All participants were required to be in CR1, be within two years of achieving CR1, and have completed all planned chemotherapy with adequate hematologic count recovery.

Fifty percent (n=11) had a normal karyotype, and 10 of these patients (91%) had further molecular testing; two had NPM1 mutation without a FLT3 internal tandem duplication mutation. Participants were stratified by risk (according to the European LeukemiaNet prognostic scoring system): eight (36%) were favorable, 10 (45%) were intermediate, three (14%) were adverse, and one (5%) was undetermined.

Participants were given six vaccinations subcutaneously biweekly over a 10-week period. The vaccine was designed to overcome the challenges of generating effective responses to WT1, such as low WT1 expression and development of immunologic tolerance, the authors explained. It consists of four WT1-derived peptides:

  • a synthetic heteroclitic short peptide to stimulate CD8+ responses (WT1-A1)
  • 2 native long peptides (331 and 427) to stimulate CD4+ responses
  • a synthetic heteroclitic long peptide to stimulate both CD4+ and CD8+ cells (122A1)

Fourteen patients (64%) received all six planned vaccinations, while 10 completed 12 vaccinations. Fifteen (68%) experienced disease relapse: 10 relapses occurred while receiving the vaccine, four after 12 vaccinations, and one at 13 months after discontinuation of therapy. Four patients’ disease relapsed after one vaccination, the researchers reported, “which is likely an insufficient amount of time to induce an immune response.”

Of the patients whose disease relapsed, 10 died because of disease progression complications. Five patients whose disease relapsed underwent hematopoietic cell transplantation (HCT) after reinduction chemotherapy. As of last follow-up (date not provided), three of these patients were still alive without evidence of recurrent disease (ranging from 11-31 months post-HCT).

At three years post-treatment, 19 patients (86%) were evaluable for survival outcomes, and nine of these patients (47%) were still alive. “The study met its prespecified endpoint of ≥34 percent overall survival (OS) at three years, justifying future clinical investigations of this WT1 vaccine,” the authors noted.

From CR1, the median disease-free survival was 16.9 months (range not provided). The median OS from diagnosis was not reached, “but is poised to reach or exceed 67.6 months (5.6 years by log-rank analysis),” the researchers wrote.

The median event-free survival (EFS) from the time of first GPS vaccination was 9.4 months (range not provided), with a probability of six- and nine-month EFS of 64 percent (95% CI 40-80) and 54 percent (95% CI 32-72), respectively.

Nineteen patients (86%) had serial reverse-transcription polymerase chain reaction measurements available, and there was no correlation between baseline WT1 transcript levels and clinical outcomes.

The researchers tested two patients whose disease relapsed early (after the first vaccine administration) and found that both had a negative CD4+ proliferative response, and one had a positive CD8+ response. “Despite the generation of CD8+ cytotoxic T lymphocyte [responses], the patient had overt clinical relapse, again suggesting either that the duration of exposure to the vaccine was inadequate to generate a clinically sufficient response or that even early CD8+ responses alone are inadequate to generate an antileukemia effect,” the investigators explained.

The overall patient population reported 244 any-grade adverse events (AEs). The most common AEs were injection-site reaction (n=10; 45.5%), skin induration (n=7; 31.8%), and fatigue (n=7; 31.8%). Two patients discontinued treatment because of probable hypersensitivity reactions that were believed to be related to GPS vaccination. No deaths were related to AEs.

“The vaccine can be administered on an outpatient basis with minimal toxicity in most patients,” the authors concluded. And, although this cohort appeared to do well, compared with historic data, “the ultimate question of clinical efficacy … will need to be addressed in a larger trial in a more homogeneous patient population.”

The study is limited by its small patient cohort, heterogeneous population, and lack of a comparator arm.

SELLAS Life Sciences Group supported the study.

The corresponding authors report financial support from SELLAS Life Sciences Group.


Maslak PG, Dao T, Bernal Y, et al. Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Advances. 2018 February 13.