PVX-410 Vaccine Safe, Immunogenic in Patients With Smoldering Multiple Myeloma

The PVX-410 vaccine is safe and has an immunogenic effect in patients with smoldering multiple myeloma (SMM) whether it is used as monotherapy or in combination with lenalidomide, results from a recent study have shown (JAMA Oncol. 2018 Aug 16. Epub ahead of print).

“This phase 1/2a nonrandomized clinical trial is the first vaccine study to our knowledge to evaluate treatment for patients with SMM at moderate or high risk of progression to MM [multiple myeloma],” said lead investigator Ajay K. Nooka, MD, MPH, FACP, Associate Professor, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, and colleagues.

Citing increasing evidence that the immune system plays a significant role in the progression of SMM, Dr Nooka and colleagues conducted a clinical trial to determine the safety, immunogenicity, tolerability, and anti-MM activity of the developmental PVX-410 multipeptide vaccine in patients with SMM.

Because Dr Nooka and colleagues hypothesized that the coadministration of lenalidomide could enhance the T-cell–mediated immune response induced by the PVX-410 vaccine, the investigation included an arm for patients receiving the vaccine plus lenalidomide.

The PVX-410 Vaccine With or Without Lenalidomide

A total of 22 patients aged 18 years and older were enrolled in the multi-center, dose escalation, 3-arm cohort trial. All patients had SMM with normal organ and marrow function, were HLA-A2–positive, and were at moderate or high risk for progression to MM. Men accounted for 64% of the trial group, and the median ages at enrollment for the monotherapy and combination cohorts were 56 years and 57 years, respectively.

Six doses of PVX-410 were emulsified in Montanide ISA 720 VG and then administered biweekly at total doses of 0.4 mg (n = 3) or 0.8 mg (n = 9). Patients in the combination cohort (n = 10), received PVX-410 at a total dose of 0.8 mg, as well as oral lenalidomide 25 mg daily every 28 days for 3 cycles spanning 21 days. Poly-ICLC 0.5 mL was also administered to every patient along with their PVX-410 doses.

According to the results, PVX-410 demonstrated immunogenicity as a monotherapy (10 of 11 patients) and as a combination treatment with lenalidomide (9 of 9 patients) via an increase in tetramer-positive cells and IFN-γ cells in the CD3+CD8+ cell population. Patients in the combination cohort had greater mean fold increases in proportions of tetramer-positive and IFN–γ-positive CD3+CD8+ T-cells, a change that Dr Nooka and colleagues said was statistically significant for IFN–γ-positive cells after 2 and 4 vaccinations.

Of the 12 patients in the PVX-410 monotherapy cohort, 7 had stable disease; 2 patients and 1 patient in the 0.4-mg and 0.8-mg cohorts, respectively, had progression (median time to progression, 36 weeks). Alternatively, 5 of 10 patients in the combination cohort had clinical responses, with 1 patient progressing (median TTP not reached).

It was also noted that there was an increase and persistence of vaccine-specific effector memory cells.

Vaccine Yields Immune Responses

Overall, the PVX-410 vaccine was well-tolerated; mild-to-moderate injection site reactions and constitutional symptoms were the most common adverse events reported.

“Findings suggest that PVX-410 multipeptide vaccine is safe and well tolerated whether given as monotherapy or combined with lenalidomide. The PVX-410 vaccine appears to consistently achieve specific, durable immune responses, which may be enhanced during treatment with lenalidomide. Further study of the vaccine is warranted, including in combination with other agents and for longer durations,” Dr Nooka and colleagues concluded.—Hina Khaliq