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. 2018 Aug 10;9:1821. doi: 10.3389/fimmu.2018.01821

Table 3.

Summary of phase 1 clinical trials of anti-B cell maturation antigen (BCMA) agents.

Name Enrollment criteria No. Prior treatment Protocol Results and efficacy Adverse event (AE)
Antibody–drug conjugate GSK2857916 (79, 80) RR MM or other hematologic malignancies expressing BCMA

  • Dose-escalating part

  • 24 (multiple myeloma)

 83%, ≥4 prior lines (alkylators, PIs, IMiDs, ±stem cell transplantation)

  • IV infusion for 1 h ever 3 weeks

  • 8 dose levels

  • 0.03, 0.06, 0.12, 0.24, 0.48, 0.96, 1.92, 3.4 mg/kg

  1. 1 MR at 0.24 mg/kg

  2. 1 VGPR, 3 PR, and 1 MR at doses ≥0.96 mg/kg

  3. Clinical benefit rate: 25%

  • Overall: 23/24 (96%), nausea (42%), fatigue (38%), anemia (29%), chills (29%), pyrexia (29%), thrombocytopenia (29%), dry eye (21%), hypercalcemia (21%)

  • Gr 3/4 SE (>10%): thrombocytopenia, anemia, and neutropenia

  • Severe AEs: 8 (in 6 patients), including 1 unresolved limbal stem cell dysfunction

  • Dose reduction: 4 patients

  • IRR: 7/24 (29%)

  • DLT (−)

  • Expansion part

  • 35

  • 50%, ≥5 prior lines (range 1–10)

  • All received PI and IMIDs

  • 97% refractory to PI

  • 91% refractory to IMiDs

  • 40% received DARA (37% refractory)

  • 89% refractory to PI and IMiDs

 IV infusion for 1 h ever 3 weeks

  1. 1 sCR, 2 CR, 15 VGPR, and 3 PR

  2. PFS: 7.9 months

  1. All patients had at least one AE

  2. Corneal events (63%), thrombocytopenia/platelet count decreased (57%), anemia (29%), AST increased (29%), and cough (26%)

  3. Gr 3/4 AEs (≥10%): thrombocytopenia (34%) and anemia (14%)

  4. Serious AEs were reported in 40% (14/35) of pts

  5. IRRs: 8 (2 Gr 1, 3 Gr 2, 3 Gr 3)
Chimeric antigen receptor (CAR) T Anti-BCMA CAR (78)

  • RRMM

  • BCMA expression by either IHC or FCM

 12 Median of 7 prior lines (range 3–13)

  1. Cy (300 mg/m2) 3 doses and Flu (30 mg/m2) 3 doses

  2. Followed by dose escalation of CAR T from (0.3, 1, 3, 9) × 106 cells/kg

 1 sCR, 2 VGPR, 1 PR, 8SD Gr 3/4 AE: lymphopenia (100%), leukopenia (100%), neutropenia (100%), anemia (50%), thrombocytopenia (50%)
bb2121 (120)

  • RRMM

  • 50% BCMA expression on plasma cells

 21 (18 evaluable for response)

  • Median of 7 prior lines (range 3–14)

  • All received auto-HSCT

  • 71% exposed to Bort/Len/Car/Pom/Dara

  • 29% with penta-refractory

  1. Lymphodepletion: flu (30 mg/m2)/Cy (300 mg/m2) daily for 3 days

  2. Followed by 1 infusion of bb2121

  3. 3 + 3 design with planned dose levels of 50, 150, 450, 800, and 1,200 × 106 CAR T cells

 Median follow-up after Bb2121 infusion: 15.4 weeks

  • 1. ORR:89% (16/18)

  • 2. ORR:100% (15/15, with 150 × 106 or more CAR T cells)

  • 4CR, 7 VGPR, 4PR

  • (4 MRD-)

  • 3. MTD: 80 × 107 CAR + T-cells

  1. CRS: 15/21 (71%), grade3 (n = 2)

  2. Gr 3/4 AE: lymphodepletion, hyponatremia (n = 4), CRS (n = 2), URI (n = 2), and syncope (n = 2)

  3. No DLT

  4. 1 death (cardiopulmonary arrest) more than 4 months after bb2121 infusion in a patient with an extensive cardiac history (disease status: sCR)
LCAR-B38M (88, 121) RRMM 19 (evaluable) ≥3 prior regimens

  1. Median infusion cells: 4.7 (0.6–7.0) × 106/kg, 3 infusions in 6 days

 1. ORR:100%, with 14 sCR, 4 VRPR, 1 PR

  1. CRS:14 (74%), Gr 3/4 (n = 2)

  2. No neurologic AEs
RRMM, with extramedullary involvement 5 (2 with EMD)

  • All relapsed after classical chemotherapy, IMiDs, and PIs

  • 3 with prior auto-HSCT

  1. Pre-CAR-T treatment: fludarabine (25 mg/m2) and cyclophosphamide (250 mg/m2) daily for 3 days (d-5–d-3)

  2. 0.62 × 106/kg (median) CAR-T cells for 3 days (d0, d2, and d6)

 1. 1 CR, 1VGPR, 3 PR

  1. Most common AEs: CRS

  2. DLT (−) TRM (−)
CART-BCMA (90) RRMM

  • 33 consented

  • 28 eligible

  • 21 infused

  • Median 7 prior lines of therapy (range 3–11)

  • 100% PI and IMIDs refractory

  • 67% Dara refractory

  • 95% had high-risk cytogenetics

  • 67% del17p or TP53 mutation

  • 29% extramedullary disease

  1. 3 split-dose infusions of CAR T cells (10, 30, 60%)

  2. 3 cohorts

    1. 1–5 × 108 CART cells (n = 9)

    2. Cy 1,500 m g/m2 + 1–5 × 107 CART cells (n = 5)

    3. Cy 1,500 mg/m2 + 1–5 × 108 CART cells (n = 7)

  • 18 (86%) received full planned dose, and 3 received 40% of dose

  • Efficacy

  • Cohort 1:1 sCR, 2 VGPR, 1 PR, 2 MR

  • Cohort 2:1 PR, 1 MR

  • Cohort 3:1 CR, 3 PR, 1 MR

  • CAR T cell expansion

  • By qPCR: 100%

  • By FCM:90%

  1. Cohort 1 data

    • Grade 3/4 SE: hypophosphatemia (n = 3), hypocalcemia (n = 2), anemia, neutropenia, lymphopenia, thrombocytopenia, hypofibrinogenemia, fatigue, pneumonia, UTI, elevated ALP and AST, hypokalemia, hypertension, and pleural effusion

  2. CRS

    • Cohort 1:8 (3 grade 3/4, with 4 receiving tocilizumab)

    • Cohorts 2/3:9 (3 grade 3, none requiring tocilizumab)

  3. Neurotoxicity

    • Cohort 1; 2 (grade 4 encephalopathy)

    • Cohorts 2/3:1 (grade 2 confusion/aphasia)

  4. DLT (−)

ALP, alkaline phosphatase; AST, aspartate aminotransferase; auto-HSCT, autologous hematopoietic stem cell transplantation; Bort, bortezomib; Car, carfilzomib; CRS, cytokine releasing syndrome; Cy, cyclophosphamide; Dara, daratumumab; DOR, duration of response; DLT, dose-limiting toxicity; EMD, extramedullary disease; Flu, fludarabine; FCM, flow cytometry; Gr, grade, IHC, immunohistochemistry; IMiD, immunomodulatory drug; IRR, infusion-related reaction; Len, lenalidomide; MoAb, monoclonal antibody; MR, minimal response; MRD, minimal residual disease; MTD, maximal tolerated dose; ORR, overall response rate; PCR, polymerase chain reaction; PD, progressive disease; PI, proteasome inhibitor; Pom, pomalidomide; PR, partial response; PRES, posterior reversible encephalopathy syndrome; RRMM, relapsed and refractory multiple myeloma; sCR, stringent complete response; SD, stable disease; URI, upper airway infection; UTI, urinary tract infection; VGPR, very good partial response.