25.4.5 Light Chain

Malignant B cells are usually light chain-restricted cells. Light chain-specific CAR

(κ.CAR) T cells were tested in a phase I clinical trial of autologous κ.CAR T cells

where four of the seven RRMM patients remained stable for 2–17 months (Ramos

et al. 2016).

25.5

Side Effects of CAR-T Therapy

Besides efficacy, early trials have demonstrated adverse clinical events associated

with CAR-T therapy such as cytokine release syndrome and encephalopathy/neuro-

toxicity. Efforts are ongoing to reveal the underlying mechanisms of these toxicities

and to manage them appropriately so as to prevent fatal complications. As compared

to other hematological malignancies, these side effects are relatively milder and less

frequent in MM.

25.6

Conclusion and Future Perspectives

CAR-T therapy is emerging as an attractive promising target for MM in the past few

years. Numerous studies on CAR-T therapy with single antigen target or in combi-

nation have shown high overall response even in RRMM patients. Besides dual-

target CAR T cell therapy for RRMM, CAR-T therapies targeting different antigens

in combination with different drugs are under preclinical or clinical studies. BCMA-

targeted CAR T cell product has demonstrated significant MM cytotoxicity and is

expected to be approved by the FDA for clinical therapy of RRMM soon. CAR T

cells targeting CD19, CD138, SLAMF7, and light chains also appear to be

promising. Future research on combining CAR-T therapy with different treatment

modalities including construction of antibody-drug conjugates and bispecific

antibodies and reducing associated toxicities will certainly aid in utilizing CAR-T

therapy in the management of MM. Emerging strategies of CAR-T with

individualized treatment options may ultimately provide a cure for myeloma

patients.

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E. S. Sinha