Characteristics of IFD in recipients of BMCA CAR T-cell therapy
| Characteristics . | Case 1 . | Case 2 . | Case 3 . | Case 4 . |
|---|---|---|---|---|
| Age, y/sex/product | 56/M/idecabtagene vicleucel | 75/F/idecabtagene vicleucel | 66/M/investigational BCMA CAR T-cell product | 77/M/ciltacabtagene autoleucel |
| Prior treatment lines | 9 | 4 | 6 | 10 |
| Prior autologous SCT | 1 | 0 | 1 | 1 |
| CAR-HT score | 4 | 1 | 2 | 5 |
| Prelymphodepletion IgG∗ | 5919 mg/dL Corrected: 49 mg/dL | 8457 mg/dL Corrected: 1857 mg/dL | 1972 mg/dL Corrected: 762 mg/dL | 309 mg/dL |
| Antifungal prophylaxis | No | Yes, fluconazole | Yes, fluconazole | Yes, fluconazole/micafungin |
| CRS/grade | Yes/grade 2 | Yes/grade 2 | Yes/grade 2 | Yes/grade 3 |
| ICANS/grade | No | Yes/grade 2 | No | Yes/grade 3 |
| Other toxicity | None | Atypical NT: parkinsonism | None | IEC-HS |
| Cumulative corticosteroid dose | 200 mg prednisone equivalent | 2998 mg prednisone equivalent | 1400 mg prednisone equivalent | 6790 mg prednisone equivalent |
| Nonsteroid treatment of IEC toxicity | Tocilizumab × 1 | Anakinra × 8, siltuximab × 1 | Tocilizumab × 2, anakinra × 1 | Tocilizumab × 3, anakinra × 3 |
| Duration of neutropenia (ANC < 500 × 103/μL), d | 4 | 2 | 2 | 15 |
| Diagnosis | Candida albicans peritonitis | Aspergillus endocarditis (autopsy) | Invasive pulmonary aspergillosis | Invasive pulmonary aspergillosis |
| Proven/probable | Proven | Proven | Probable | Probable |
| Timing after CAR T cells, d | 18 | 104 | 6 | 41 |
| Treatment | Fluconazole × 14 d | - | Voriconazole × 3 mo | Voriconazole initiated |
| Outcome/case details | Complete response, alive at 1 year | Patient died with parkinsonism and Stenotrophomonas sepsis; focal aspergillus infection involving the papillary cardiac muscle on autopsy | Complete response, alive at 1 year | Patient died within 24 hours of positive serum GMN result from shock, thought to be related to progressive IEC-HS, MRSA VAP, and invasive aspergillosis. |
| Characteristics . | Case 1 . | Case 2 . | Case 3 . | Case 4 . |
|---|---|---|---|---|
| Age, y/sex/product | 56/M/idecabtagene vicleucel | 75/F/idecabtagene vicleucel | 66/M/investigational BCMA CAR T-cell product | 77/M/ciltacabtagene autoleucel |
| Prior treatment lines | 9 | 4 | 6 | 10 |
| Prior autologous SCT | 1 | 0 | 1 | 1 |
| CAR-HT score | 4 | 1 | 2 | 5 |
| Prelymphodepletion IgG∗ | 5919 mg/dL Corrected: 49 mg/dL | 8457 mg/dL Corrected: 1857 mg/dL | 1972 mg/dL Corrected: 762 mg/dL | 309 mg/dL |
| Antifungal prophylaxis | No | Yes, fluconazole | Yes, fluconazole | Yes, fluconazole/micafungin |
| CRS/grade | Yes/grade 2 | Yes/grade 2 | Yes/grade 2 | Yes/grade 3 |
| ICANS/grade | No | Yes/grade 2 | No | Yes/grade 3 |
| Other toxicity | None | Atypical NT: parkinsonism | None | IEC-HS |
| Cumulative corticosteroid dose | 200 mg prednisone equivalent | 2998 mg prednisone equivalent | 1400 mg prednisone equivalent | 6790 mg prednisone equivalent |
| Nonsteroid treatment of IEC toxicity | Tocilizumab × 1 | Anakinra × 8, siltuximab × 1 | Tocilizumab × 2, anakinra × 1 | Tocilizumab × 3, anakinra × 3 |
| Duration of neutropenia (ANC < 500 × 103/μL), d | 4 | 2 | 2 | 15 |
| Diagnosis | Candida albicans peritonitis | Aspergillus endocarditis (autopsy) | Invasive pulmonary aspergillosis | Invasive pulmonary aspergillosis |
| Proven/probable | Proven | Proven | Probable | Probable |
| Timing after CAR T cells, d | 18 | 104 | 6 | 41 |
| Treatment | Fluconazole × 14 d | - | Voriconazole × 3 mo | Voriconazole initiated |
| Outcome/case details | Complete response, alive at 1 year | Patient died with parkinsonism and Stenotrophomonas sepsis; focal aspergillus infection involving the papillary cardiac muscle on autopsy | Complete response, alive at 1 year | Patient died within 24 hours of positive serum GMN result from shock, thought to be related to progressive IEC-HS, MRSA VAP, and invasive aspergillosis. |
F, female; GMN, galactomannan; M, male; MRSA VAP, methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia; NT, neurotoxicity.
Corrected IgG levels (M-spike component subtracted from total IgG level to approximate polyclonal and functional IgG) were reported in patients with IgG MM.