Posted: Monday, May 9, 2022
When joined with vaccine-specific co-stimulated T cells, an antimyeloma idiotype (Id)-keyhole limpet hemocyanin (KLH) vaccine appears to result in immune reconstruction in CD4-positive and CD8-positive T cells, according to research presented in Blood. Muzaffar H. Qazilbash, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues hypothesized that this combination immunotherapy may enhance therapeutic efficacy in this patient population.
The randomized phase II trial included 36 patients who received either KLH monotherapy (n = 20) or Id-KLH vaccine plus autologous transplantation, two vaccine boosters, and vaccine-specific co-stimulated T cells expanded ex vivo (n = 16). Half of the patients in the Id-KLH arm (n = 8) and 30% of those in the KLH arm (n = 6) achieved complete remission. No meaningful difference in 3-year progression-free survival was noted (59% [with KLH] vs. 56% [with Id-KLH]). T-cell immune reconstruction genes experienced a stronger reaction following treatment in the Id-KLH arm than in the monotherapy arm. Post-vaccination upregulation of activation genes, induction of effector function, and generation of memory CD8-positive T cells were observed only in the Id-KLH arm, according to the investigators.
Patients in either treatment arm who achieved a response were also found to experience upregulation of T-cell activation genes. All patients experienced a decline in expression of CD8-positive T-cell exhaustion markers versus baseline. The authors proposed that this may indicate an immunosuppressed phenotype in patients with multiple myeloma who have undergone treatment.
“Combining this treatment with a checkpoint inhibitor or other immunomodulatory therapies may further improve the efficacy of this approach,” concluded the authors.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.