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Brief Report
December 13, 2018

Assessment of Safety and Immunogenicity of PVX-410 Vaccine With or Without Lenalidomide in Patients With Smoldering Multiple Myeloma: A Nonrandomized Clinical Trial

Author Affiliations
  • 1Department of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
  • 2University of Texas MD Anderson Cancer Center, Houston
  • 3Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
  • 4Dana-Farber Cancer Institute, Boston, Massachusetts
  • 5OncoPep Inc, North Andover, Massachusetts
JAMA Oncol. 2018;4(12):e183267. doi:10.1001/jamaoncol.2018.3267
Key Points

Questions  Is a vaccination approach with PVX-410 multipeptide vaccine safe and immunogenic with or without lenalidomide in human leukocyte antigen A2–positive patients with moderate- to high-risk smoldering myeloma?

Findings  The PVX-410 vaccine with or without lenalidomide was well tolerated. Immune responses were seen, as indicated by an increase in percentage of tetramer-positive cells and interferon γ–positive cells in the CD3+CD8+ cell population, which was further enhanced in combination with lenalidomide.

Meaning  These results demonstrate immune responses to a vaccination strategy in a patient population with smoldering myeloma; further evaluation of PVX-410 and lenalidomide among patients with smoldering myeloma who are at a risk of progression is warranted.

Abstract

Importance  Increasing evidence suggests the significance of the role of the immune system in the progression of smoldering multiple myeloma (SMM) to symptomatic multiple myeloma (MM). Boosting the immune system via vaccination in the earlier, asymptomatic SMM stage may provide a novel strategy to prevent or slow progression to active MM.

Objective  To determine the safety, tolerability, immunogenicity, and anti-MM activity of the PVX-410 multipeptide vaccine with or without lenalidomide.

Design, Setting, and Participants  This 3-cohort phase 1/2a multicenter dose-escalation study accrued 22 adults (≥18 years) with SMM with normal organ/marrow function who were human leukocyte antigen A2-positive and at moderate or high risk of progression to MM.

Interventions  Patients received 6 doses of PVX-410 emulsified in Montanide ISA 720 VG, 0.4 mg total (0.1 mg/peptide) (n = 3) or 0.8 mg total (0.2 mg/peptide) (n = 9), biweekly via subcutaneous injection. In the combination cohort (n = 10), patients also received three 21-day cycles of lenalidomide, 25 mg, orally daily every 28 days. All patients received 0.5 mL (1 mg) poly-ICLC (2 mg/mL) via intramuscular injection with each PVX-410 dose.

Main Outcomes and Measures  Adverse events (AEs) were evaluated using the Common Terminology Criteria for Adverse Events, version 4.03. PVX-410–specific T lymphocytes by flow cytometry to assess tetramer and interferon (IFN)-γ response. Disease response was assessed by investigators using the International Myeloma Working Group (IMWG) and modified European Group for Bone Marrow Transplantation (EBMT) criteria.

Results  Overall, 14 (64%) patients were men and the median age at enrollment was 56 years in the monotherapy and 57 years in the combination cohorts (overall range, 39-82 years). Six of 12 patients in the monotherapy and 9 of 10 in the combination cohorts were at moderate risk. The PVX-410 vaccine was well tolerated. The most common AEs were mild-to-moderate injection site reactions and constitutional symptoms. Of note, PVX-410 was immunogenic as monotherapy (10 of 11 patients) and in combination with lenalidomide (9 of 9 patients), as demonstrated by an increase in percentage of tetramer-positive cells and IFN-γ cells in the CD3+CD8+ cell population. The combination resulted in greater mean fold increases in proportions of CD3+CD8+ T cells that were tetramer-positive and IFN–γ-positive, statistically significant for IFN–γ-positive cells after 2 and 4 vaccinations. An increase and persistence of vaccine-specific effector memory cells was noted. In total, 7 of 12 patients in the PVX-410–alone cohort had stable disease with 2 of 3 (low-dose cohort) and 1 of 9 of the target-dose cohort progressing (median TTP, 36 weeks), whereas 5 of 12 patients in the combination cohort showed, clinical response, with 1 patient progressing (median TTP not reached).

Conclusions and Relevance  Overall, these results suggest that the vaccine is safe and immunogenic in this patient population and support continued study of PVX-410 in SMM.

Trial Registration  ClinicalTrials.gov identifier: NCT01718899

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