Randomized phase II trial of dendritic cell/myeloma fusion vaccine with lenalidomide maintenance after upfront autologous hematopoietic cell transplantation for multiple myeloma: BMT CTN 1401 Journal Article
| Authors: | Chung, D. J.; Shah, N.; Wu, J.; Logan, B.; Bisharat, L.; Callander, N.; Cheloni, G.; Anderson, K.; Chodon, T.; Dhakal, B.; Devine, S.; Dutt, P. S.; Efebera, Y.; Geller, N.; Ghiasuddin, H.; Hematti, P.; Holmberg, L.; Howard, A.; Johnson, B.; Karagkouni, D.; Lazarus, H. M.; Malek, E.; McCarthy, P.; McKenna, D.; Mendizabal, A.; Nooka, A.; Munshi, N.; O’Donnell, L.; Rapoport, A. P.; Reese, J.; Rosenblatt, J.; Soiffer, R.; Stroopinsky, D.; Uhl, L.; Vlachos, I. S.; Waller, E. K.; Young, J. W.; Pasquini, M. C.; Avigan, D. |
| Article Title: | Randomized phase II trial of dendritic cell/myeloma fusion vaccine with lenalidomide maintenance after upfront autologous hematopoietic cell transplantation for multiple myeloma: BMT CTN 1401 |
| Abstract: | Purpose: Vaccination with dendritic cell (DC)/multiple myeloma (MM) fusions has been shown to induce the expansion of circulating multiple myeloma–reactive lymphocytes and consolidation of clinical response following autologous hematopoietic cell transplant (auto-HCT). Patients and Methods: In this randomized phase II trial (NCT02728102), we assessed the effect of DC/MM fusion vaccination, GM-CSF, and lenalidomide maintenance as compared with control arms of GM-CSF and lenalidomide or lenalidomide maintenance alone on clinical response rates and induction of multiple myeloma–specific immunity at 1-year posttransplant. Results: The study enrolled 203 patients, with 140 randomized posttransplantation. Vaccine production was successful in 63 of 68 patients.At1year,ratesofCRwere52.9%(vaccine)and50%(control; P = 0.37, 80% CI 44.5%, 61.3%, and 41.6%, 58.4%, respectively), andratesofVGPRorbetterwere85.3%(vaccine)and77.8%(control; P = 0.2). Conversion to CR at 1 year was 34.8% (vaccine) and 27.3% (control; P = 0.4). Vaccination induced a statistically significant expansion of multiple myeloma–reactive T cells at 1 year compared with before vaccination (P = 0.024) and in contrast to the nonvaccine arm (P = 0.026). Single-cell transcriptomics revealed clonotypic expansion of activated CD8 cells and shared dominant clonotypes between patients at 1-year posttransplant. Conclusions: DC/MM fusion vaccination with lenalidomide did not result in a statistically significant increase in CR rates at 1 year posttransplant but was associated with a significant increase in circulating multiple myeloma–reactive lymphocytes indicative of tumor-specific immunity. Site-specific production of a personalized cell therapy with centralized product characterization was effectively accomplished in the context of a multicenter cooperative group study. ©2023 The Authors; Published by the American Association for Cancer Research. |
| Keywords: | controlled study; genetics; lenalidomide; clinical trial; antineoplastic agent; multiple myeloma; phase 2 clinical trial; dendritic cell; randomized controlled trial; antineoplastic combined chemotherapy protocols; granulocyte macrophage colony stimulating factor; dexamethasone; hematopoietic stem cell transplantation; dendritic cells; multicenter study; transplantation, autologous; autotransplantation; granulocyte-macrophage colony-stimulating factor; humans; human |
| Journal Title: | Clinical Cancer Research |
| Volume: | 29 |
| Issue: | 23 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2023-12-01 |
| Start Page: | 4784 |
| End Page: | 4796 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-23-0235 |
| PUBMED: | 37463058 |
| PROVIDER: | scopus |
| PMCID: | PMC10690096 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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