Idiotype Vaccine Plus Adoptive T-Cell Transfer Shows Enhanced Immune Reconstitution in Myeloma
A randomized phase 2 trial in 36 multiple myeloma patients demonstrated that idiotype-KLH vaccination combined with autologous costimulated T cells produced significantly more robust CD4+ and CD8+ immune reconstitution compared to KLH control, as measured by a 594-gene NanoString panel. While clinical response differences did not reach significance, the gene expression data support further investigation of combined vaccine and adoptive immunotherapy strategies.
The original study
A randomized phase 2 trial of idiotype vaccination and adoptive autologous T-cell transfer in patients with multiple myeloma.
- Authors
- Qazilbash MH, Saini NY, Cha SC, Wang Z, Stadtmauer EA, Baladandayuthapani V, et al.
- Journal
- Blood
- Type
- Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial
- PMID
- 34521108
Original abstract
We hypothesized that combining adoptively transferred autologous T cells with a cancer vaccine strategy would enhance therapeutic efficacy by adding antimyeloma idiotype (Id)-keyhole limpet hemocyanin (KLH) vaccine to vaccine-specific costimulated T cells. In this randomized phase 2 trial, patients received either control (KLH only) or Id-KLH vaccine, autologous transplantation, vaccine-specific costimulated T cells expanded ex vivo, and 2 booster doses of assigned vaccine. In 36 patients (KLH, n = 20; Id-KLH, n = 16), no dose-limiting toxicity was seen. At last evaluation, 6 (30%) and 8 patients (50%) had achieved complete remission in KLH-only and Id-KLH arms, respectively (P = .22), and no difference in 3-year progression-free survival was observed (59% and 56%, respectively; P = .32). In a 594 Nanostring nCounter gene panel analyzed for immune reconstitution (IR), compared with patients receiving KLH only, there was a greater change in IR genes in T cells in those receiving Id-KLH relative to baseline. Specifically, upregulation of genes associated with activation, effector function induction, and memory CD8+ T-cell generation after Id-KLH but not after KLH control vaccination was observed. Similarly, in responding patients across both arms, upregulation of genes associated with T-cell activation was seen. At baseline, all patients had greater expression of CD8+ T-cell exhaustion markers. These changes were associated with functional Id-specific immune responses in a subset of patients receiving Id-KLH. In conclusion, in this combination immunotherapy approach, we observed significantly more robust IR in CD4+ and CD8+ T cells in the Id-KLH arm, supporting further investigation of vaccine and adoptive immunotherapy strategies. This trial was registered at www.clinicaltrials.gov as #NCT01426828.