The PVX-410 multipeptide vaccine was safe and immunogenic with or without lenalidomide in patients with moderate- to high-risk smoldering myeloma, according to the results of a phase I/IIa study published in JAMA Oncology.
“The PVX-410 vaccine appears to consistently achieve specific, durable immune responses, which may be enhanced during treatment with lenalidomide,” wrote Ajay K. Nooka, MD, MPH, of the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center, and colleagues. “Further study of the vaccine is warranted, including in combination with other agents and for longer durations.”
The mechanisms that cause smoldering multiple myeloma to progress are currently unknown, but it is theorized that the immune system may play a role, according to the study. Boosting the immune system using vaccination may prevent or slow disease progression.
Nooka and colleagues tested this theory using the PVX-410 vaccine, a human leukocyte antigen A2–restricted multipeptide cancer vaccine. The vaccine is composed of four 9-mer chemically synthesized peptides from unique regions of three multiple myeloma–associated antigens.
Patients enrolled in the study were assigned to one of three cohorts. Three patients received 6 doses of 0.4 mg of the vaccine; 9 patients received 6 doses of 0.8 mg of the vaccine; and 10 patients also received combination treatment with three 21-day cycles of lenalidomide to see if it could maximize antitumor activity. All patients also received 0.5-mL poly-ICLC via intramuscular injection with each vaccine dose.
The median age of patients in the vaccine arm was 56 years, while the median age in the combination arm was 57 years. One in four patients completed study treatment.
Overall, the vaccine was considered to be well tolerated. The most common adverse events were mild-to-moderate injection site reactions and constitutional symptoms.
The vaccine was immunogenic in both the monotherapy cohorts (10 of 11 patients) and the combination arm (9 of 9 patients), for an immune response in 95% of patients. This was shown by an increase in percentage of tetramer-positive cells and interferon (IFN)-γ cells in the CD3+, CD8+ cell population.
“Greater mean fold increases over baseline in proportions of CD3+ and CD8+ peripheral blood mononuclear cells that were PVX-410 peptide tetramer–positive, IFN-γ–positive, interleukin-2–positive, or tumor necrosis factor α–positive were seen with the combination vs monotherapy,” the researchers reported. “Combination therapy also resulted in higher percentages at all four posttreatment measurement times of tetramer-positive, CD3+, and CD8+ peripheral blood mononuclear cells exhibiting an effector memory cell phenotype.”
In the monotherapy arm, 7 of 12 patients had stable disease; 2 out of 3 patients in the lower-dose cohort and 1 of 9 patients in the higher-dose cohort progressed. In the combination cohort, 5 of 12 patients had a clinical response and only 1 patient progressed.
“There appeared to be a relationship between clinical response and the magnitude of immune response, with responders having a significantly greater immune response compared with those who progressed,” the researchers wrote. “Specifically, patients showing a greater than 10-fold response over baseline at more than two time points were more likely to demonstrate a clinical response or stable disease at the last study visit.”