Novel DNA Vaccine Reduces Tumor Clones, Favorably Alters Immune Microenvironment in Patients with Untreated Smoldering WM

A novel idiotype (scFv-CCL20) DNA vaccine was associated with favorable perturbation of the immune microenvironment in patients with untreated smoldering Waldenstrom macroglobulinemia (WM), according to a study presented by Sheeba Thomas, MD, of The University of Texas MD Anderson Cancer Center in Houston, at the 62nd American Society of Hematology Annual Meeting & Exposition.

A total of nine patients with smoldering WM were treated with the idiotype DNA vaccine between 2016 and 2019 at doses of 500 µg (n=3) and 2,500 µg (n=6). The median age at time of study enrollment was 67 years (range, 56-78 years), and the median time from diagnosis to the first vaccination was 26.5 months.

While one patient has been lost to follow up, eight were alive at the median follow-up of 38 months. Stable disease was maintained six patients, and three progressed to symptomatic WM at eight, 25, and 28 months. All patients completed therapy.

Overall, there were no reports of dose-limiting toxicities or grade 4 adverse events (AEs). Approximately 10 months following the third vaccination, one patient experienced grade 3 pleural effusion and leukopenia. The grade 1/2 AEs reported in more than three patients included leukopenia (n=6), nausea (n=5), anemia (n=4), increased creatinine (n=4), and fatigue (n=4).

The vaccine treatment was associated with significant reductions in the number of clonal B-cells in the bone marrow compartment of two patients who maintained stable disease. In addition, treatment with the DNA vaccine was associated with increases in monocytes in the tumor microenvironment in patients with stable disease.

Also, the investigators found increases in T-cell receptor (TCR) clonal expansions in a TCR sequence analysis, which they suggest was consistent with a vaccine effect.

“The immunologic changes observed suggest response to this vaccine, and warrant further investigation in a phase II trial, possibly in combination with immune checkpoint blockade,” the researchers concluded.