Table 2.
CAR-T cell therapies for extramedullary disease in multiple myeloma
| CAR target | Patient group | Patient (n)/ EMD (n) | Agent Name | Line of previous treatment | Efficacy | Survival | Adverse events | Ref |
|---|---|---|---|---|---|---|---|---|
| BCMA | RRMM |
152 (47) (EM-E: 47) |
Ide-cel, cilta-cel |
median 6 | EMD vs. non-EMD: ORR: 58% vs. 96%; CR: 28% vs 56% |
EMD vs. non-EMD: mPFS: 5.1 months, 12.4 months; mOS: 12.2 months, 27.5 months |
EMD vs. non-EMD: CRS: 81%, 78%; ≥ grade 3 CRS: 11%, 3%; ICANS: 36%, 25%; ≥ grade 3 ICANS: 6%, 7% | [57] |
| BCMA | RRMM | 269 (112) |
Ide-cel, Cilta-cel |
median 6 | EMD predicts early relapse/progression post-CAR-T (HR: 1.92) | ND | ND | [62] |
| BCMA | RRMM | 20 (5) | Cilta-cel | median 8 | Extramedullary lesions disappeared: 80% | ND | ND | [63] |
| BCMA | RRMM | 97 (13) | Cilta-cel | median 6 | ND | EMD vs. all patients: mDOR: 12.9 months, 23.3 months | ND | [64] |
| BCMA | RRMM | 128 (50) | Ide-cel | median 6 | ORR of EMD worse than no EMM (no specifics) | ND | ND | [65] |
| BCMA | RRMM | 69 (15) | Anti-BCMA and anti-CD19 CAR-T cells | median 4 | EMD: ORR: 80%; |
EMD vs. non-EMD: mPFS: 8.3 months, 21.4 months mOS: 12.3 months, NR; |
ND | [66] |
| BCMA | RRMM | 351 (84) | Ide-cel | median 6 |
EMD vs. non-EMD: 90d-ORR: 52%, 82% |
EMD vs. non-EMD: mPFS: 5.3 months, 11.1 months; mOS: 14.8 months, 26.9 months; |
EMD vs. non-EMD: ≥ grade 3 CRS: 2%, 1.5%; ≥ grade 3 ICANS: 1%, 5% |
[58] |
| BCMA | RRMM | 61 (27) (EM-B:10, EM-E:7, Both: 10) | Anti‐BCMA CAR‐T cells | median 3 |
EMD vs. non-EMD: CR: 59%, 81% |
EMD vs. non-EMD: 1-year PFS rate: 34.4% vs. 60.2% |
ND | [67] |
| BCMA | RRMM | 61 (25) | Anti‐BCMA CAR‐T cells | median 4 |
EMD vs. non-EMD: ORR: 84.00%, 94.44% ≥ CR: 36.00%, 61.11% |
EMD vs. non-EMD: mPFS: 121 days, 361 days; mOS: 248 days, 1024 days |
EMD vs. non-EMD: CRS: 84%, 100%; ≥ grade 3 CRS:12%, 27.8%; ICANS: 0, 2.8% |
[68] |
| BCMA | RRMM | 33 (9) | Ide-cel | median 7 | EMD vs. non-EMD: ORR: 89%, 83% | ND | ND | [69] |
| BCMA | RRMM | 17 (5) | LCAR-B38M | ≥ 3 | EMD vs. non-EMD: ORR: 80%, 92% | EMD: 1-year PFS rate: 20% |
EMD vs. non-EMD: ≥ Grade 3 CRS: 60%, 33% |
[70] |
| BCMA | RRMM | 25 (7) | Humanized anti‐BCMA CAR‐T cells | median 7 | EMD: ORR: 57% | ND | ND | [71] |
| BCMA | RRMM | 18 (5) | CT103A | median 4 | EMD vs. non-EMD: ORR: 100%, 100% |
EMD vs. non-EMD: 1-year PFS rate: 20% vs. 79.1%; 1-year OS rate: 60% vs. 79.1% |
EMD vs. non-EMD: ≥ Grade 3 CRS: 0, 38.5% |
[72] |
| BCMA | RRMM |
30 (18) (EM-E: 18) |
Anti‐BCMA CAR‐T cells | median 4 | EMD vs. non-EMD: ORR: 77.78%, 90% | EM-E: median OS: 243 days | ND | [73] |
| BCMA | RRMM | 21 (12) (EM-B:6, EM-E:6) | Humanized anti‐BCMA CAR‐T cells | ≥ 5 | EM-E vs. EM-B vs. non-EMD: ORR: 83.33%, 83.33%, 88.89% | EM-E vs. EM-B vs. non-EMD: 180 days-PFS rate: 50%, 83.33%, 88.89%; 180 days-OS rate: 83.33%, 100%, 88.89%; 360 days-PFS rate: 16.67%, 66.67%, 66.67%; 360 days-OS rate: 33.33%, 83.33%, 88.89% | EM-E vs. EM-B vs. non-EMD: CRS: 100%, 100%, 100%; ≥ grade 3 CRS: 50%, 33.3%, 0; ICANS: 50%, 16.7%, 11.1%; ≥ grade 3 ICANS: 0, 0, 0 | [74] |
| BCMA | RRMM | 49 (11) | HDS269B | ≥ 3 |
EMD vs. non-EMD: ORR: 64%, 82% |
EMD vs. non-EMD: mOS: 5.0 months, 24.0 months; mPFS: 3.0 months, 10.5 months | ND | [75] |
| BCMA | RRMM | 211 (95) | Ide-cel | median 6 |
EMD vs. non-EMD: Progressed ≤ 3 Months: 27.3%, 14.6% |
EMD is associated with worse PFS ([HR] = 1.71, 95% CI: 1.16–2.51) and OS (HR = 1.69, 95% CI: 1.00–2.86) | ND | [76] |
| BCMA | RRMM | 2 (2) | CT103A | 3 | Both achieved sCR | Survival over 13 and 10 months, respectively | EMD: Grade 2 CRS: 1 patient; No ICANS | [61] |
| BCMA | RRMM | 20 (7) | Humanized anti-BCMA CAR-T cells | ≥ 5 |
EMD vs. non-EMD: ORR: 71.43%, 84.61%; Extramedullary lesions: sCR/CR: 85.71% |
EMD vs. non-EMD: 180 days-PFS rate: 42.9%, 84.6%; 360 days-PFS rate: 28.6%, 72.5%; 180 days-OS rate:71.5%, 92.3%; 180 days-OS rate: 28.6%, 81.0% |
EMD vs. non-EMD: ≥ grade 3 CRS: 42.9%, 0 ICANS: 28.6%, 7.7%; ≥ grade 3 ICANS: 0, 0 |
[77] |
| BCMA | RRMM | 134 (59) (EM-B: 25; EM-E: 34) |
Ide-cel, cilta-cel and other |
median ≥ 4 | EM-E vs. EM-B vs. non-EMD: ORR: 76.5%, 92%, 88% |
EM-E vs. EM-B vs. non-EMD: mPFS: 9 months, 21.4 months, 24.2 months; mOS: 24 months, NR, NR |
ND | [78] |
| GPRC5D | RRMM | 33 (11) | Anti-GPRC5D CAR-T cells | median 4 | EMD vs. non-EMD: ORR: 91%, 91% | ND | ND | [79] |
| GPRC5D | RRMM | 10 (4) | OriCAR-017 | median 5.5 |
EMD vs. non-EMD: ORR: 100%, 100% |
ND | ≥ grade 3 CRS and ICANS: 0 | [80] |
| BCMA-CS1 | RRMM | 16 (6) | CS1-BCMA CAR-T cells | median 4 | Extramedullary lesions disappeared: 66.7% | ND | ND | [81] |
| BCMA-CD38 | RRMM | 23 (9) | BM38 CAR-T cells | median 4 | EMD: sCR: 44.4%; Extramedullary lesions disappeared: 55.6% | ND | ND | [82] |
| BCMA-CD19 | NDMM | 22 (12) (EM-B:9, EM-E:3) | GC012F | none | EMD: sCR: 100%; MRD-: 100% | ND | ND | [83] |
| BCMA-CD38 | RRMM | 16 (8) | BCMA-CD38 CAR-T cells | ≥ 2 | EMD: sCR: 75%; PD: 25%, Extramedullary lesions disappeared: 62.5% | ND | ND | [84] |
| BCMA-CD19 | RRMM | 31 (31) (EM-E:31) | Anti-BCMA and anti-CD19 CAR-T cells | median 4 |
EMD: ORR: 64.5%; ≥ CR: 25.8% |
EMD: mPFS: 5.0 months; mOS: 9.7 months |
EMD: CRS: 83.9%; ≥ grade 3 CRS: 25.8%; ICANS: 9.7%; ≥ grade 3 ICANS: 6.5% | [85] |
| BCMA- GPRC5D | RRMM | 21 (4) | BCMA-GPRC5D CAR-T cells | median 3 | EMD: ORR: 75% | ND | ND | [86] |
Abbreviations: EMD, extramedullary disease; RRMM, relapsed/refractory multiple myeloma; NDMM, newly diagnosed multiple myeloma; EM-B, EMD, bone-associated; EM-E, extramedullary extraosseous; ORR, overall response rate; CR, complete response; sCR, stringent complete response; VGPR, very good partial response rate; PD, progressive disease; PFS, progression-free survival; mOS, median overall survival; mPFS, median progression-free survival; ND, no data; NR, not reached; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; MRD, minimal residual disease; Ide-cel, Idecabtagene vicleucel; Cilta-cel, Ciltacabtagene autoleucel; CAR-T, chimeric antigen receptor T; BCMA, B-cell maturation antigen; GPRC5D, G protein-coupled receptor class C group 5 member D; CS1, also named SLAMF7, Signaling Lymphocytic Activation Molecule Family Member 7; mDOR, median duration of response; HR, hazard ratio