Table 1.
Summary of early phase clinical trials of anti-BCMA CAR T-cell therapy.
| Name (Sponsor) | Structure | Phase | Key Inclusion Criteria (Summarized) |
Key Exclusion Criteria (Summarized) |
Basic Data of Study Population | Protocol | Efficacy | Adverse Events (AEs) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Condi-Tioning | CAR-T Cell Dosing | ORR | MRD- | Survival | Other | CRS or Neuro-Toxicity | Others | ||||||
| Ant-BCMA CAR [63] (NIH) | 1. γ-retroviral vector 2. Murine scFv 3. Co-stimulation domain: CD28 4. Culture medium: Anti-CD3 MoAb and IL-2 |
Phase 1 (NCT02215967) | 1. 18–73 years 2. ≥3 different prior treatment. 3. BCMA expression on >50% of PC by either IHC or FCM. 4. Measurable disease 5. ECOG 0–2 |
1. Any anticoagulants (except aspirin) 2. Pregnant or breast-feeding 3. Active systemic infection 4. CNS involvement 5. Pregnant or lactating women |
1. RRMM patients, n = 24. 2. Median 9.5 lines of prior therapy (range 3–19) in highest dose level group (n = 16). 3. High-risk cytogenetics: 40% of evaluable patients at highest dose. |
Cy (300 mg/m2) 3 doses and Flu (30 mg/m2) 3 doses | Dose escalation from (0.3, 1, 3, 9) × 106 CAR T cells/kg. a. 10 patients received 0.3–3 × 106. b. 16 patients received 9 × 106. (2 patients received 2 infusions) |
(16 evaluable) ORR:81% (2 sCR, 8 VGPR, 3 PR) |
100% (at 9 × 106, n = 11), by 8-color FCM. | Median EFS: 31 weeks | (16 evaluable) 1. CRS: 15 (93.75%), including 2 grade 4, 4 grade 3, 7 grade 2, and 2 grade 1 2. 6 (38%) need vasopressor support for hypotension |
(16 evaluable) 1. Grade 3–4 AEs: leikopenia (93.75%), anemia (68.75%), thrombocytopenia (62.5%) |
|
| bb2121 (Idecabtagene vicleucel) [64] (Celgene) |
1. Lentivirus vector 2. Murine scFv 3. Co-stimulation domain: 4-1BB 4. Culture medium: Anti-CD3/CD28, OKT3 |
Phase 1 (NCT02658929) | 1. ≥18 years 2. ECOG 0 or 1 3. ≥3 different prior lines of therapy 4. Measurable disease 5. ≥50% BCMA expression on PCs (IHC). |
1. CNS disease 2. Inadequate organ function (heart, liver, renal) 3. Inadequate bone marrow function 4. Active systemic infection within 72 h 5. Pregnant or lactating women 6. Plasma cell leukemia |
1. RRMM patients, n = 33. 2. Median 7 lines of prior therapy (range 3–14). All received auto-HSCT; 71% received anti-CD38 MoAb; 29% with penta-refractory 3. High-risk cytogenetics: 45% |
Flu (30 mg/m2)/Cy (300 mg/m2) daily for 3 days | One infusion 3+3 design with dose levels of 5, 15, 45, 80 and 120 × 107 bb2121 cells. |
85% (28/33), including 3 CR and 12 sCR. | (total 18): 16/16 (100%) at 10−4 nucleated cell (exclude 2 no response), by NGS |
1. Median DOR: 10.9 months 2. Median PFS: 11.8 months |
Median time to first PR or better: 1.0 month | 1. CRS: 25 (76%), grade 1 or 2 (n = 23, 70%), grade3 (n = 2, 6%) 2. Duration of CRS:5 days 3. Neurologic toxic effects: 14 (42%), including 13 grade 1–2 (39%) and 1 grade 4 (3%). |
1. Grade 3–4 AEs (>10%): Neutropenia, leukopenia, anemia, thrombocytopenia, lymphopenia. 2. No DLT 3. Infection: 14 (42%), including 2 grade 3. |
| bb21217 [65] (bluebird bio) | 1. Lentivirus vector 2. Murine scFv 3. Co-stimulation domain: 4-1BB 4. Add PI3K inhibitor bb007 in ex vivo culture |
Phase 1, (CRB-402; NCT03274219) | 1. ≥18 years old. 2. ECOG 0 or 1. 3. ≥3 different prior lines of therapy. 4. Measurable disease. 5. ≥50% BCMA expression on PCs (IHC). |
1. CNS disease 2. Inadequate organ function(heart, liver, renal) 3. Inadequate bone marrow function 4. Active systemic infection within 72 h 5. Pregnant or lactating women |
1. RRMM patients, n = 22 2. Median 7 lines of prior therapy (range 4–17). 3. 18 patients had prior ASCT; 7 had high-risk cytogenetics. 19 received prior daratuzumab, 13 had previously bortezomib, lenalidomide, carfilzomib, pomalidomide, and daratumumab. 4. Eleven patients had high tumor burden (≥50% bone marrow PCs) before infusion. |
Flu (30 mg/m2)/Cy (300 mg/m2) daily for 3 days | One infusion with planned dose levels of 150, 450, 800, and 1200 × 106 bb21217 cells. | 83% (15/18), 6 of them progressed | 100% (10/10), at 10−5 nucleated cells by NGS at month 1. | 1. CRS: 13 (59.1%), including 5 Grade 1, 7 Grade 2, 1 Grade 3. All responded to supportive care. 2. 5 neurotoxicity, including 1 grade1, 2 grade 2, 1 grade 3, and 1 grade 4 |
1. No treatment related mortality | ||
| BCMA CAR-T [66] (HRAIN Biotechnology, Henan University) | 1. γ-retrovirus vector 2. Co-stimulation domain: 4-1BB 3. Safety switch (truncated EGFR) |
Phase 1 (NCT03093168) | 1. 18–70 years 2. ≥3 lines of prior therapy (PI, or IMiDs, or both) 3. ≥5% BCMA expression on PCs (IHC). 4. ≥90 days after HSCT 5. ECOG 0–4 |
1. With CNS symptoms 2. Another malignancy 3. Active hepatitis B or C, HIV infections 4. Severe heart or respiratory diseases |
1. RRMM patient, n = 17 (infused), 14 (evaluable for efficacy and safety) | Flu (25 mg/m2)/Cy (300 mg/m2) daily for 3 days (d-5 to -3) | One infusion of CAR-T cell: 9 × 106/kg (d0) | 79%, 3 sCR, 4 CR and 2 MRD- (2 VGPR) | 1 sCR and 1 VGPR with the ongoing objective response ≥15 months. | 1. Grade≥ 3 CRS: 1(7%) 2. Grade ≥ 3 neurotoxicity: 1(7%) |
1. Grade≥ 3 non-hematologic AEs: 2 pneumonia (14%), 2 hypophosphatemia (14%), and 2 hypocalcemia (14%) | ||
| BCMA CAR T (FCARH143) [67] (Fred Hutchinson Cancer Research Center) | 1. Lentivirus vector 2. Fully human scFv 3. Co-stimulation domain: 4-1BB |
Phase 1 (NCT03338972) |
1. ≥21 years 2. RRMM (≥10% CD138+ BM PCs, and ≥5% BCMA expression by FC). 3. ECOG 0–2 4. Measurable disease. |
1. With another primary malignancy 2. Active hepatitis B or C, HIV infections 3. Uncontrolled active infection 4. CNS symptoms 5. Pregnant or lactating women |
1. RRMM patient, n = 7 Cohort A: 10–30% MM cells in BM Cohort B: >30% MM cells in BM (Median % : 58% (20 to >80)) 2. Median 8 lines of prior therapy (range 6–11) 3. All with ≥1 high-risk cytogenetics (71% had ≥2) 4. 71% with prior ASCT, 43% with allo-SCT |
Cy + Flu (d-4 to -2) | CAR T cell dosing (d0) (1:1 ratio of CD4+:CD8+ BCMA CAR T cells) Cohort A: 5 × 107 Cohort B: 15 × 107 |
100% (at 28 days) |
One relapsed with BCMA- PC clone | 1. No neurological toxicity 2. CRS: 6 (85.7%), all grade 2 or lower |
1. No DLTs | ||
| BCMA-CAR T [68] (Huazong University) | 1. Lentivirus vector 2. Murine scFv 3. Co-stimulation domain: CD28 |
Phase 0 (ChiCTR-OPC-16009113) |
1. 18 to 70 years. 2. ECOG 0–2. 3. Adequate organ function 4. With BCMA+ PC. |
1. Pregnancy and nursing females 2. Active hepatitis B or C, HIV infections 3. With mental disorders |
1. 28 patients (26 RRMM, 1PCL, 1POEMS) 2. BCMA expression level Strong (≥50%): 22 patients Weak (<50%): 6 patients |
Cy + Flu | 5.4 to 25 × 106 CAR T cells/kg | Strong: 87% (73% CR) Weak:100% (CR or VGPR) |
Median DFS (strong vs weak): 296 vs 64 days3.Median OS (strong vs weak): Not defined vs 206.5 days | 1.4 grade 3CRS. | 1. All toxicities were fully reversible | ||
| CART-BCMA [36] (University of Pennsylvania-Norvartis) | 1. Lentivirus vector 2. Fully human scFv 3. Co-stimulation domain: 4-1BB 4. Culture medium: Anti-CD3/CD28 beads and IL-2 |
Phase 1 (NCT02546167) | 1. ≥18 years. 2.RRMM (≥3 prior treatment, or ≥2 prior regimens with double refractory to PI and IMiDs). 3. Adequate organ functions 4. ECOG 0–2 5. Measurable disease |
1. Pregnant or lactating 2. Active hepatitis B or C, HIV infections 3. Active or uncontrolled infection 4. Uncontrolled medical or psychiatric diseases |
1. RRMM patients, 34 consented, 29 eligible, 25 received infusion 2. Median 7 lines of prior therapy (range 3–13) 96% refractory to IMiDs and PIs 72% refractory to daratumumab 44% penta-refractory 3. 96% with at least one high-risk cytogenetics (68% del17p or TP53 mutation) 4. Median 65% of MM cells on bone marrow biopsy 28% with extramedullary disease. |
With (Cy) or without conditioning treatment | 1. 3 split-dose infusions of CAR T cells (10%, 30%, 60%) 2. 3 cohorts a. 1–5 × 108 CART cells b. Cy 1500m g/m2 + 1–5 × 107 CART cells c. Cy 1500 mg/m2 + 1–5 × 108 CART cells |
(≥PR): 48%, with 55% in 5 × 108 CART-BCMA cells. a. Cohort 1: 4 (44%, 1 sCR, 2 VPGR, 1 PR) b. Cohort 2: 1 (20%, 1 PR) c. Cohort 3: 7 (64%, 1 CR, 3 VGPR, 3 PR) in cohort 3. |
Overall median OS: 502 days (359 days, 502 days, and not reached for cohorts 1, 2, and 3, respectively) | Detected CAR T cells: in 20 (100%) and 14 (82%) evaluable patient at 3 and 6 months post infusion. | 1. CRS: 22 (88%); 8 grade 3–4 (all 1–5 × 108 dose) Medium time to CRS:4 days Medium duration; 6 days Medium hospitalization: 7 days 7 (28%) received anti-IL-6 agents 2. Neurotoxicity (n = 8, 32%): 5 grade 1–2, 3 grade 3–4 |
1. All grade ≥ 3 AEs: 24 (96%) 2. Grade 3/4 SE: leukopenia (44%), neutropenia (44%), lymphopenia (36%) 3. One grade 5 AE |
|
| CART-BCMA [69] (Shenzhen Pregene Biopharma) | 1. One anti-BCMA single-domain antibody derived from the alpaca, and humanized 2. Co-stimulation domain: 4-1BB |
Phase 1 (NCT03661554) |
1. 18–75 years 2. RRMM, BCMA+ 3. ECOG 0–2 4. Adequate organ function |
1. Pregnant or lactating 2. Active hepatitis B or C, HIV infections 3. Severe infection 4. Poor organ function |
1. RRMM patients, n = 16(infused) 2. Median 10 lines of prior therapy |
Cy (300–600 mg/m2, d-5, -4) and Flu (30 mg/m2, d-5 to d-3) | One infusion of 2–10 × 106 CAR cells/kg(d0) | 1. 13 patients without EM lesion: 84.6% (d28), 100% (10th weeks, n = 7), including 3 sCR/CR, 1 VGPR, and 3 PR 2. Three patients with EM lesion: All PR at d28 |
1. 2 patients with grade3–4 CRS (0–2 in other patients) | ||||
| CART-BCMA/CART-19 [70,71] (First Affiliated Hospital of Soochow University) | 1. Co-stimulation domain: OX40 and CD28 2. Lentiviral vector 3. Culture medium: Anti-CD3 beads |
Phase 1/2 (NCT 03196414) |
1. 18–75 years 2. CD138+ or BCMA+ RRMM 3. Adequate organ function |
1. Pregnant or lactating 2. Active hepatitis B or C, HIV infections 3. Uncontrolled active infection 4. Poor organ function |
1. RRMM patients, n = 28 2. All resistant to PIs, IMiDs, or both 3. Average of 3 (2–8) lines of prior treatment |
Cy 300mg/m2 and Flu × 3 days (d-5,-4 and -3) | CART-19 (1 × 107/kg on day 0) and CART-BCMA cells (40% on d1 and 60% on d2) | 92.6% (88.9% PR or better), 11 CR or sCR, 8 VGPR, 5 PR and 1 MR. | Median OS: 16 months | 1. CRS:100%, 19 grade 1–2, 7 grade 3, and 2 grade 4 | 1. Other AEs: fatigue (100%), cytopenia (100%), anemia (100%), and prolonged APTT (82.1%) | ||
| Phase 1/2 (NCT 03455972) |
1. 18–65 years old MM patients eligible for auto-HSCT. 2. High-risk MM (stage III or failed to achieve PR after prior treatment.). 3. All with BCMA >50% without CD19 expression on PCs. 4. ECOG 0–2. 5. Adequate organ function. |
1. Pregnant or lactating 2. Active hepatitis B or C, HIV infections 3. Uncontrolled active infection 4. History of myocardial infarction |
1. Cohort 1: 9 patients, all BCMA> 50% without CD19 expression | CART-19 (1 × 107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused d14 to d20 after ASCT | 100% (post CAR-T treatment), 3CR and 6 VGPR | 37.5% after ASCT to 66.7% after CAR-T therapy | 1. CRS: 100%, all grade 1–2 2. No serious CRS or neurologic complications |
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| CART-BCMA CTL119 [72] (Abramson Cancer Center) | 1. 4-1BB co-stimulatory domain 2. Lentiviral vector |
1. Phase A (PhA): MM patients responding (≥MR) to ≥3rd line therapy (or ≥2nd line if exposed to all major agents) 2. Phase B (PhB): High-risk patients. |
1. 6 enrolled PhA patients were infused 2. 4 enrolled PhB patients were infused (2 CART-BCMA alone, 2 CART-BCMA + CTL119) 3. Prior lines: 1–9 4. BM PC(%): 1–91 |
Flu (30 mg/m2) + Cy (300 mg/m2) × 3 days | 1. Phase A: CART-BCMA + CTL119 Phase B: CART-BCMA +/− CTL119 2. CAR-T infusion (5 × 108 CAR+ cells in 3 divided doses, 10%, 30%, and 60%) after conditioning treatment |
80%, 1 CR, 4 VGPR, 3 PR in 10 evaluable (6 PhA, 2 PhB combo, and 2 PhB mono) | 1. One PhA patient died due to CNS progression before infusion. 2. All exhibited in vivo CAR-T cell expansion |
(10 evaluable) CRS:80%, all grade 1–2 |
(10 evaluable) 8 fatigue, 8 cytopenia, 6 anemia, and 5 coagulopathy. |
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| CT053 [73] (CARsgen Therapeutics Co.) | 1. Fully human scFv2. 4-1BB co-stimulatory domain | Phase 1 (NCT03716856, NCT03302403, and NCT03380039) |
1. 18–70 years old. 2. RRMM 3. BCMA+ PC (FCM or IHC) 4. Measurable disease. 5. ECOG 0–1. |
1. lymphocytes transduction <10%, expansion after αCD3/CD28 costimulation <5-fold 2. Hepatitis C or HIV infections 3. Uncontrolled active infection |
1. RRMM patients, n = 24 (All with ≥50% BCMA expression on MM cells) 2. Median 4.5 prior regimen (range 2–11) 3. 41.7% prior ASCT 4. 45.8% with EM lesions |
Flu (20–25 mg/m2) + Cy (300–500 mg/m2) daily for 2–4 days | 1.5 × 108 CT053 cell infusion after conditioning treatment | 87.5% (21/24), including 14 sCR and 5 CR | 85% (17/20), ≤10−4 nucleated cells | 1. 3 neurotoxicity (all grade 1) 2. CRS: 15 (3 grade 1, 12 grade 2), 8 received tocilizumab |
1. No DLT 2. Grade ≥ 3 AEs: leukopenia, thrombocytopenia, lymphopenia. |
||
| CT103A [74] (Nanjing Iaso Biotherapeutics Co, Ltd) | 1. Fully human scFv 2. With CD8a hinger and 4-1BB co-stimulatory domain 3. Lentiviral vector |
Phase 0 (ChiCTR1800018137) |
1. 18–70 years old. 2. BCMA+ PCs 3. Proper organ function |
1. Pregnant or lactating 2. Active hepatitis B or C, HIV infections 3. Uncontrolled active infection 4. Poor organ function |
1. RRMM, n = 16 2. Median 4 prior therapy (range 3–5), including 4 patients after murine BCMA CAR-T treatment, and 5 with EM lesions or PCL. |
Cy + Flu | 3 + 3 dose-escalation (3 doses at 1, 3, 6 × 106/kg) | 1. 100% (6 CR/sCR) within first 2 weeks. 2. 3 sCR and 1 VGPR in 4 prior BCMA CAR-T cell treated patients |
100% in all 15 patients, ≤10−4 nucleated cells by FCM. | CT103A cells detectable in 12/16 patients, at the last evaluation | 1. All developed CRS (10 grade 1–2, 5 grade 3, 1 grade 4) | ||
| JCARH125 [75] (Juno Therapeutics, Inc.) | 1 Fully human scFv 2. Co-stimulation domain: 4-1BB 3. Lenti-viral vector |
Phase 1/2 (EVOLVE; NCT 03430011) | 1. ≥18 years old 2. RRMM (≥3 prior regimens, including PI, IMiD, anti-CD38 MoAb, and auto-HSCT). 3. ECOG 0–1 4. Adequate renal, BM, liver, lung, and heart function 5. Measurable disease |
1. EM lesion, PCL, WM, or POEMS syndrome. 2. CNS involvement by malignancy 3. Untreated or active infection 4. Poor heart function |
1. RRMM patients (19 enrolled, 13 treated) Initial 8 patients 1. Median 10 lines of prior therapy (range 4–15), including 50% refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide and an anti-CD38 mAb. 2. 88% had prior ASCT |
Flu (30 mg/m2)/Cy (300 mg/m2) daily for 3 days | One infusion of JCARH125 (2 dose levels: 50 and 150 × 106 CAR+ T cells) | Evaluable patients (n = 3), 1PR, 2 sCRs Unconfirmed patients (n = 5): 1 CR, 2 VGPR, 1 PR, 1 MR |
(8 evaluable) 1. CRS: 6 (75%), all grade 1or 2 Median onset of CRS: 9 days (range 4 – 10) Median duration of CRS: 4.5 days (range 2 – 19 days) 2. Neurotoxicity: 3 (2 grade1, 1 grade 3) |
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| LCAR-B38M [76,77] and [78,79] (Nanjing Legend Biotech Co) | 1. Lentivirus vector 2. Bispecific anti-BCMA variable fragments of llama heavy-chain antibodies 3. Co-stimulation domain: 4-1BB 4. Culture medium: IL-2 |
Phase 1/2 (LEGEND-2; NCT 03090659) | 1. 18–80 years 2. RRMM (≥3 prior regimens) 3. BCMA+ PC (FCM or IHC) |
1. Pregnant or lactating 2. Active hepatitis B or C, HIV infections 3. Uncontrolled medical illness |
(One of four centers) 1. RRMM patients, n = 57 2. Median 3 prior regimens (range1–9), including prior PIs (68%), IMiDs (86%), and both (60%) |
3 doses of Cy 300 mg/m2 | Five days after Cy, LCAR-B38M CAR T cells (median cell dose = 0.5 × 106 cells/kg, [range, 0.07–2.1 × 106]), split into in 3 infusions (20, 30, and 50% of total dose) given over 7 days. | ≥PR: 88% (50/57), including 42 CR (39 MRD-), 2 VGPR, 6 PR. |
92.8% (39/42) in CR patients, by 8-color FCM | 1. Median DOR: 22 months 2 Median PFS: 20 months (all patients); 28 months (MRD- patients). 3. The median OS: NR |
Medium time to response: 1.2 month | 1. CRS: 51 (90%), grade 1 (47%), grade 2 (35%); grade 3 (7%, n = 4). Medium time to CRS; 9 days 2. Neurotoxicity: 1 (grade 1), dosed at 1.0 × 106 CAR+ T cells/kg |
1. AE reported in all patients. Pyrexia (91%), thrombocytopenia (49%), and leukopenia (47%) 2. Grade ≥3 AE:37 (65%), leukopenia (30%), thrombocytopenia (23%), and increased aspartate aminotransferase (21%). 3. One grade 5 AE: pulmonary embolism |
| Phase 1/2 (LEGEND-2; NCT 03090659) | 1. 18–80 years 2. RRMM (≥3 prior regimens) 3. BCMA+ PC (FCM or IHC) |
1. Pregnant or lactating 2. Active hepatitis B or C, HIV infections 3. Uncontrolled medical illness |
(The other three centers) 1. RRMM patients, n = 17 2. ≥3 prior regimens (range3-11), including prior PIs (88%), IMiDs (82%), and both (71%), ASCT (47%) 3.Five patients with EM |
Cy 250 mg/m2 + Flu 25 mg/m2 for 3 days (n = 8) or Cy 300 mg/m2 for 3 days (n = 9). | LCAR-B38M cell infusion 5d after the start of the conditioning regimen. (3 infusions in Cy + Flu vs 1 infusion in Cy group) Mean dose: 0.7 × 106 (range, 0.2–1.5 × 106 cell/kg) |
1. 88% (15/17), including 14 CR and 1 VGPR 2. With EM lesion: 100%, including 3 sCR, 1VGPR, and 1 MR | 100% in all CR patients (8-color FCM) | 1. Median PFS: 12 (all) and 18 (MRD-) months 2. Median OS: NR (all and MRD-) |
Cy + Flu group had better PFS and lower relapse rate | 1. CRS:100%, including 10 grade 1/2, 6 grade 3, and 1 grade 5. 9 patients received IL-6R inhibitor treatment. 2. No neurotoxicity |
1. AE reported in all patients. Pyrexia (100%), cytopenia (82%), impaired liver function (100%) 2. Tumor lysis syndrome: 3(18%) |
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| MCARH171 [80] (Memorial Sloan Kettering Cancer Center) | 1. Human derived anti-BCMA scFv 2. Co-stimulation domain: 4-1BB 3. Retroviral vector 4. Safety switch (truncated EGFR) 5. Culture medium: Phytohemagglutinin or anti-CD3/CD28 beads and IL-2 |
Phase 1 | 1.≥18 years. 2. RRMM (≥2 prior regimens including an IMiD and a PI) 3. Adequate organ function |
1. Poor performance 2. Poor organ function 3. HIV or active hepatitis B or hepatitis C infection |
1. RRMM patients, n = 11 2. Median 6 lines of prior therapy (range 4–14), all received IMiD, anti-CD38 MoAb, and ASCT 3. 82% with high-risk cytogenetics |
(1) Cy 3000 mg/m2 single dose or (2) Flu 30 mg/m2 daily and Cy 300 mg/m2 daily for 3 days | 1-2 divided doses of MCARH171 with 4 dose levels (1) 72 × 106, (2) 137 × 106, (3) 475 × 106, (4) 818 × 106 viable CAR T cells | 1. ORR:64% 2. 100% ORR observed in 5 patients received higher doses (≥ 450 X106) |
Median DOR:106 days | (10 evaluable) 1. CRS: 6 (60%), 4 grade 1–2, and 2 grade 3. 2. No grade ≥3 neurotoxicity |
(10 evaluable) 1. No DLTs |
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| JNJ-68284528 [81] (Janssen) | 1. Lentivirus vector 2. Bispecific anti-BCMA variable fragments of llama heavy-chain antibodies 3. Co-stimulation domain: 4-1BB 4. Culture medium: IL-2 (Identical to LCAR-B38M) |
Phase 1b/2 (CARTITUDE-1/MMY2001; NCT03548207) | 1. ≥18 years old 2. RRMM (≥3 prior regimens or double refractory to a PI and IMiD, and received an anti-CD38 MoAb) 3. Measurable disease 4. ECOG 0–1 |
1. Previous CAR-T treatment (+) 2. Previous anti-BCMA treatment (+) 3. Poor heart function 4. CNS MM involvement |
1. RRMM patient, n = 25 (infused) 2. Median prior lines of treatment : 5 (range 3–16) 3. 88% triple-refractory to a PI, IMiD, and anti-CD38 antibody, 72% penta-exposed, and 36% penta-refractory |
Flu (30 mg/m2)/Cy (300 mg/m2) daily for 3 days | One infusion of JNJ-4528 (target 0.5–1 × 106 /kg) 5–7 days after conditioning treatment | (21 evaluable) 1. ORR:91%, 4 sCR, 2CR, 7 VGPR, and 6PRs |
(15 evaluable) 1. 10 MRD- at the 10−5 level, 2 at the 10−4 level, and 3 had unidentified clones. | 1. 80% of patients had grade 1–2 CRS, with 1 grade 3 and 1 grade 5. 2. CRS events occurring at a median of 7 days (range 2–12) post-infusion with a median duration of 3 days (range 1–60). 4. Tocilizumab and steroid used in 91% and 27% of patients (n = 22). |
1. Treatment related AE: CRS (88%), neutropenia (80%), anemia (76%), and thrombocytopenia (72%) 2. Grade ≥3 AEs: neutropenia (76%), thrombocytopenia (60%), and anemia (48%) |
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| P-BCMA-101 [82] (Poseida Therapeutics, Inc.) | 1. Centyrin-based binding domain (small, fully human) 2. CD3ζ/4-1BB signaling domain 3. In vitro transcribed mRNA and plasmid DNA 4. Safety switch (truncated EGFR) 5. Tscm phenotype |
Phase 1 (NCT 03288493) |
1. ≥18 years old. 2. RRMM (received PI and IMiDs) 3. Measurable disease 4. Adequate organ function |
1. Pregnant or lactating 2. Active hepatitis B or C, HIV infections 3. Uncontrolled medical illness 4. With PCL, WM, or POEMS syndrome 5. Active second malignancy |
1. RRMM patients, n = 12 2. Rang of prior lines: 3–9 3. 100% refractory to PI, IMiD, and daratumumab 4. High-risk cytogenetics: 64% |
Flu (30 mg/m2)/Cy (300 mg/m2) daily for 3 days | 1. 1 infusion of P-BCMA-101. 2. 3 + 3 design with planned dose levels of 48, 50, 55, 118, 122, 124, 143, 155, 164, 238, 324 and 430 × 106 CAR T cells. |
1. 66.7%(n = 3), 1 PR and 1 near CR 2. Yet evaluable patients (n = 6): 1 sCR, 1VGPR, and 3PRs |
1. CRS:1 (grade 2) 2. No neurotoxicity |
1. No unexpected/off-target toxicities related to treatment. | |||
The inclusion or exclusion criteria were summarized from published articles or ClinicalTrials.gov website.