Potential clinical implications of MM immune types for the application of immune therapy
| . | IP . | IE . | IS . | ID . | IR . |
|---|---|---|---|---|---|
| Proposed defining feature(s) | T-cell hot spots with infiltration and Clec9a DCs, lack of terminal differentiation in T-cell clones | T cells at tumor margins without infiltration and lack of Clec9a DCs | Inhibitory myeloid infiltration, immune-suppressive cells, and T-cell exhaustion | Systemic and regional lymphoid depletion | Loss of T-cell redirection target and resistance to immune recognition |
| Clinical aspects | Expected favorable course earlier in disease evolution | Biology possibly similar to extramedullary plasmacytomas | Potentially diverse mechanisms | Lymphopenia, ? with impaired hematopoiesis, extreme age, frailty, and prior extensive chemotherapy | Target-specific loss or mutations in targets for T-cell redirection |
| Response to T-cell redirection | Yes, durable responses | Yes, but may not be durable | Yes, but not durable | Unlikely but high risk of CAR T-cell manufacturing failure | No, but resistance may be limited to specific therapies |
| Possible solutions/therapeutic goals | Target early eradication of residual disease | Enhance T-cell entry and DC or NK recruitment | Combinations to overcome suppression and optimal combinations may be pathway/mechanism specific | Direct tumor targeting and restore lympho-hematopoiesis | Alternate targets or combinatorial targeting and alternate immune cells (eg, NK/NKT) |
| . | IP . | IE . | IS . | ID . | IR . |
|---|---|---|---|---|---|
| Proposed defining feature(s) | T-cell hot spots with infiltration and Clec9a DCs, lack of terminal differentiation in T-cell clones | T cells at tumor margins without infiltration and lack of Clec9a DCs | Inhibitory myeloid infiltration, immune-suppressive cells, and T-cell exhaustion | Systemic and regional lymphoid depletion | Loss of T-cell redirection target and resistance to immune recognition |
| Clinical aspects | Expected favorable course earlier in disease evolution | Biology possibly similar to extramedullary plasmacytomas | Potentially diverse mechanisms | Lymphopenia, ? with impaired hematopoiesis, extreme age, frailty, and prior extensive chemotherapy | Target-specific loss or mutations in targets for T-cell redirection |
| Response to T-cell redirection | Yes, durable responses | Yes, but may not be durable | Yes, but not durable | Unlikely but high risk of CAR T-cell manufacturing failure | No, but resistance may be limited to specific therapies |
| Possible solutions/therapeutic goals | Target early eradication of residual disease | Enhance T-cell entry and DC or NK recruitment | Combinations to overcome suppression and optimal combinations may be pathway/mechanism specific | Direct tumor targeting and restore lympho-hematopoiesis | Alternate targets or combinatorial targeting and alternate immune cells (eg, NK/NKT) |