Multiple myeloma (MM) is a plasma cell multiple myeloma hematologic malignancy that is being used as a major disease model for evaluating immunotherapy, targeted radiotherapy, and novel small-molecule approaches. Its therapeutic landscape includes CAR-T cell therapy, CD46-directed radioimmunotherapy and antibody-drug conjugates, proteasome inhibition, and engineered oncolytic vaccinia virus platforms. Recent literature highlights movement of CAR-T into relapsed/refractory, newly diagnosed, and even frontline settings, with reports of superior progression-free survival and high response/MRD negativity in clinical programs. In murine MM models, an oncolytic vaccinia virus encoding a CD47 nanobody suppressed tumor growth and extended survival, and HsClpP activators were also explored as a therapeutic strategy. Protein-disease association work identified TNFSF13 (APRIL) and TNFRS13B (TACI) as linked to MM biology, supporting its classification as a B-cell/plasma cell malignancy with actionable immune and proteostasis pathways.
Immunotherapy and CAR-T
- CAR-T therapy has produced “remarkable advances” in this hematologic malignancy, with updates spanning relapsed/refractory, newly diagnosed, and frontline treatment contexts. (PMID:41589415; PMID:41975476)
- A 2026 Journal of Hematology & Oncology review (PMID:41975476) highlighted CARTITUDE-4 as reporting superior progression-free survival in MM.
- Idecabtagene vicleucel improved outcomes in MM patients in KarMMa-3, supporting BCMA-directed cellular therapy in this disease. (PMID:41975476)
- iMMagine-1 reported high response rates and MRD negativity in MM, indicating deep clinical responses with CAR-T approaches. (PMID:41975476)
Targeted radiotherapy and antibody-drug conjugates
- CD46-directed therapy was evaluated in MM, including CD46-targeted radioimmunotherapy and alpha-particle therapy. (PMID:41569419)
- Synergistic treatment with CD46-targeted antibody-drug conjugates was reported for MM, suggesting a combinatorial targeting strategy. (PMID:41569419)
- These CD46-based approaches were presented in a 2026 Clinical Cancer Research study, extending targeted delivery concepts to plasma cell malignancy. (PMID:41569419)
Oncolytic virotherapy and immune modulation
- In murine MM models, an engineered oncolytic vaccinia virus encoding a CD47 nanobody suppressed tumor growth and extended survival. (PMID:41858619)
- The same study positioned MM as a disease model for testing oncolytic vaccinia virus therapy and immune checkpoint modulation. (PMID:41858619)
- The virus was combined with bortezomib, a proteasome inhibitor used in MM, to help overcome resistance. (PMID:41858619)
Molecular targets and proteostasis
- Proteome-wide Mendelian randomization identified TNFSF13 (APRIL) and TNFRS13B (TACI) as protein associations in MM, reinforcing its B-cell malignancy biology. (PMID:41859349)
- HsClpP activators were investigated as a therapeutic indication for MM, pointing to mitochondrial proteostasis as a druggable axis. (PMID:41785829)
- Novel 2-(methylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine derivatives were discovered as HsClpP activators for MM therapy in a 2026 European Journal of Medicinal Chemistry study. (PMID:41785829)