Multiple myeloma pathogenesis is marked by incredibly complex processes that range beyond primary or acquired genetic alterations, with factors in the marrow microenvironment playing a significant role in promoting clonal survival, changes to native immune response and ultimate disease progression. Signaling and communication among malignant plasma cell and tumor microenvironment fosters the necessary milieu which can also support therapeutic resistance to antimyeloma agents. In the era of transformative impact of T cell redirecting (TCR) therapies, including chimeric antigen receptor (CAR) T cell, bispecific (BsAb) and emerging trispecific (TsAb) antibodies, the quality of nascent immunity, and factors impacting T cell fitness and exhaustion are emerging as key considerations that are influencing therapeutic sequencing among the rapidly expanding roster of TCR/engaging treatments. These concepts do not only impact therapeutic competence and outcomes of T cell redirecting therapies, but also modulate the risk of acquired infections.

This research topic welcomes original research papers, review and mini-review articles, commentaries, systemic reviews, data reports and brief research reports which expand on:

--Relevant insights in the space of bone marrow and microenvironmental immune milieu in myeloma
--Balance of pro-inflammatory cytokines/chemokines in myeloma
--Identification of biomarkers predictive of treatment response and prolonged therapeutic durability of immune based therapies in myeloma
--Alternate and innovative immune therapeutic strategies in myeloma
--Myeloma vaccination or treatment sequencing approaches that minimize T cell exhaustion and promote T cell fitness
--Factors that promote T and NK cell function, as well as alter the balance and activity of myeloid derived suppressor and other inhibitory cells
--The role of existing monoclonal and BsAbs, emerging TsAb, approved and evolving CAR T cell therapies in supporting the efficacy and safety of TCRs
--The role therapeutic classes such as immunomodulatory drugs, cereblon E3 ligase modulatory drugs, and Exportin 1 inhibitors in supporting the efficacy and safety of TCRs

Please note that (1) Prof. Muhamed Baljevic has been a consultant for Pfizer, AbbVie, J&J, BMS/Celgene, Janssen Biotech, J&J, Sanofi-Genzyme, Pfizer, Prothena, AbbVie, and Parexel International; (2) Dr Jack Khouri has a consulting or advisory role for J&J, Prothena, Legend Biotech, Kite and conducts research for J&J, Prothena, Ascentage, Karyopharm, GPCR; (3) Dr Adam Binder is a speaker, receives research funding and partakes in the advisory board for Johnson and Johnson, is a speaker for Karyopharm, receives research funding and partakes in the advisory board for Sanofi, and receives research funding from Regeneron and Bristol Myers Squibb; (4) Prof. Douglas Sborov is associated with Bristol Myer Squibb, Pfizer, Sanofi, Janssen, Opna Bio, Arcellx, Regeneron, GSK, Caribou and Abbvie.

Also note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.

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Immunity and Immunotherapy in Multiple Myeloma