Cellular Immunotherapy for Multiple Myeloma Advancing Rapidly

Theodore Bosworth


January 30, 2017

In This Article

Activated Marrow-Infiltrating Lymphocytes

Marrow-infiltrating lymphocytes (MILs) for myeloma have been in development for more than 10 years, with the first clinical trial published in 2015.[1] Like CAR and TCR therapies, MILs are developed from T cells recovered from MM patients, expanded ex vivo, and then reinfused as a cellular therapy. In the case of MILs, the T cells targeted for harvesting are myeloma specific. Various strategies have been used to enhance ex vivo expansion and, once infused, trafficking these cells to the bone marrow and then persistent antimyeloma activity. This includes the enrichment of MILs for long-lived memory T-cell phenotypes. The published trial confirmed activity; new data confirm persistence.

Specifically, in long-term follow-up of a clinical study of MILs initiated in 2007, myeloma antigen-specific T cells were recovered from the bone marrow up to 7 years after infusion.[2] According to the investigating team at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, led by Ivan Borrello, MD, those who achieved CR subsequent to the MIL infusion were the most likely to demonstrate persistent MILs. Conversely, bone marrow biopsies conducted in those who did not achieve CR demonstrated loss of myeloma antigen-specific T cells in most cases.

Conceptually related to tumor-infiltrating lymphocytes (TILs), which have demonstrated durable clinical remissions in melanoma, MILs are administered after a myeloablative therapy such as melphalan. Their activity in the bone marrow microenvironment creates the potential for a low relative risk of off-target effects. According to Dr Stadtmauer, an ongoing randomized trial, if positive, may rapidly advance this strategy into the clinical realm, but both he and the Johns Hopkins investigators have suggested that adding an additional immunotherapy, such as a tumor vaccine, may be a strategy that helps sustain the persistence of an antimyeloma effect.


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