Risk factors associated with an increased risk of post–CAR T-cell cytopenias
| . | Risk factors . | Comments . | References . |
|---|---|---|---|
| Disease-related features | Underlying disease (BCP-ALL > B-NHL) | Evidence concerning the rate of cytopenias in patients with MM still emerging | 39 |
| Disease burden prior to CAR T-cell infusion (progressive disease, high LDH) | Especially BM disease burden | 14,102 | |
| Prior therapies | Number of prior therapy lines | Associated with baseline hematopoietic function | 39 |
| Prior hematopoietic stem cell transplantation | 104 | ||
| Bridging therapy | 41 | ||
| Baseline marrow status | BM infiltration | 42,40 | |
| Preexisting cytopenias | Particularly preexisting thrombocytopenia | 13,33 | |
| Clonal hematopoiesis of indeterminate potential (CHiP)? | Has been linked to increased inflammation, potential emerging risk factor | 46,47,85 | |
| Baseline inflammatory status | Increased serum CRP | 13 | |
| Increased serum ferritin | 13 | ||
| CAR T-cell product and postinfusion risk factors | Costimulatory molecule (CD28 > 41BB) | May also reflect differences in lymphodepletion dosing (cyclophosphamide dosing) | 39 |
| Type of construct (tandem > single target) | 39 | ||
| Severe CRS | 33,34 | ||
| Sustained increased inflammatory markers | 33 | ||
| Oligoclonal T-cell expansion | In select patients; the success of autologous stem cell boost argues against this as a general mechanism | 35 | |
| Active infection | Mainly viral or in case of concomitant sepsis | 105 | |
| CRS/MAS or IEC-HS | Cytopenia as overlapping symptomology | 10,11,106 |
| . | Risk factors . | Comments . | References . |
|---|---|---|---|
| Disease-related features | Underlying disease (BCP-ALL > B-NHL) | Evidence concerning the rate of cytopenias in patients with MM still emerging | 39 |
| Disease burden prior to CAR T-cell infusion (progressive disease, high LDH) | Especially BM disease burden | 14,102 | |
| Prior therapies | Number of prior therapy lines | Associated with baseline hematopoietic function | 39 |
| Prior hematopoietic stem cell transplantation | 104 | ||
| Bridging therapy | 41 | ||
| Baseline marrow status | BM infiltration | 42,40 | |
| Preexisting cytopenias | Particularly preexisting thrombocytopenia | 13,33 | |
| Clonal hematopoiesis of indeterminate potential (CHiP)? | Has been linked to increased inflammation, potential emerging risk factor | 46,47,85 | |
| Baseline inflammatory status | Increased serum CRP | 13 | |
| Increased serum ferritin | 13 | ||
| CAR T-cell product and postinfusion risk factors | Costimulatory molecule (CD28 > 41BB) | May also reflect differences in lymphodepletion dosing (cyclophosphamide dosing) | 39 |
| Type of construct (tandem > single target) | 39 | ||
| Severe CRS | 33,34 | ||
| Sustained increased inflammatory markers | 33 | ||
| Oligoclonal T-cell expansion | In select patients; the success of autologous stem cell boost argues against this as a general mechanism | 35 | |
| Active infection | Mainly viral or in case of concomitant sepsis | 105 | |
| CRS/MAS or IEC-HS | Cytopenia as overlapping symptomology | 10,11,106 |
BCP-ALL, B-cell precursor acute lymphoblastic leukemia; B-NHL, B-cell non-Hodgkin lymphoma; CRP, C-reactive protein; LDH, lactate dehydrogenase; MAS, macrophage activation syndrome.