PVX-410 vaccine alone or with lenalidomide for patients with smoldering multiple myeloma

Smoldering multiple myeloma (SMM) is a precursor form of multiple myeloma (MM). Patients (pts) need to be monitored regularly to identify early signs of MM onset. Currently, most SMM pts do not receive any form of treatment. In 2014 the International Myeloma Working Group (IMWG) identified a group of SMM pts with a higher risk of developing MM. Early treatment for these “high-risk” SMM pts is recommended to prevent any MM-related end-organ damage¹.

A possible means of delaying or preventing SMM progressing to MM, is by increasing the immune reaction against MM antigens using vaccines. PVX-410 is a human leukocyte antigen (HLA) A2 multi-peptide cancer vaccine that specifically targets three MM-associated proteins: X-box binding protein 1 (XBP1), syndecan-1, and cell surface glycoprotein SLAM family member 7 (SLAMF7).

Ajay K. Nooka from the Winship Cancer Institute, Emory School of Medicine, Atlanta, US, and colleagues, examined the safety and immunogenicity of PVX-410 as a monotherapy or in combination with lenalidomide (len) in a phase I/IIa clinical trial. To be eligible to participate in the trial, pts had to be positive for HLA-A2 and have a moderate or high risk of progression to MM. The results of the study were published in JAMA Oncology in August 2018².

Results are presented as PVX-410 monotherapy vs PVX-410 with lenalidomide.

Study Design:

• Number of pts = 22
• Number of male pts = 14
• Median age = 56 vs 57 (overall range, 39-82)
• Pts per treatment = 12 vs 10
• Moderate risk pts = 6/12 vs 9/10
• Three treatment cohorts based on dose of PVX-410: low-dose cohort = 0.4 mg (n = 3 pts); target-dose cohort = 0.8 mg (n = 9 pts); combination cohort = 0.8 mg plus len
• PVX-410 was administered in 6 doses every two weeks via subcutaneous injection in combination with an adjuvant [0.5 ml poly-ICLC (2 mg/ml)] via intramuscular injection
• Lenalidomide = 3 cycles of 25 mg (orally) daily for 21 days, of a 28-day cycle
• Follow-up time = 12 months

Key Data:

• Number of pts completing treatment = 12/12 vs 9/10
• Adverse events (AEs) = mild-to-moderate injection site reactions and constitutional symptoms
• Number of pts achieving immune response = 20/21 (95%) (10/11 vs 9/9)
• Stimulation with PVX-410 led to:
  • an increase in PVX-410-specific tetramer positive cells
  • an increase in interferon (IFN)–γ positive T cells
• Combination treatment had a greater effect on enhancing the immune response, compared to monotherapy, as evidenced by 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
  • tumor necrosis factor α positive
• PVX-410 as a monotherapy or in combination with len significantly increased the percentage of effector memory CD8+ T cells in tetramer positive T cell populations
• Best clinical response: monotherapy cohort = stable disease (SD), 7/12 pts; 5/12 pts progressed within the 12-month follow-up period; combination cohort = partial response, 1/9 pts; minimal response, 4/4 pts; SD, 4/4 pts
• Median time to progression (TTP): low-dose cohort = 2/3 pts; target-dose cohort = 1/9 pts (median TTP, 36 weeks); combination cohort 1/12 pts (median TTP, not reached)

Conclusions

This study shows that the PVX-410 vaccine is safe and can increase immunogenicity in a pt population with SMM. Future clinical trials with a larger number of pts will determine the efficacy of PVX-410 combined with len in delaying progression to MM.