Immune-based therapies in MM
| Therapy | Structure | Trial stage | Dosage and effective rate | Adverse reactions | Approved usage |
|---|---|---|---|---|---|
| Tim3 inhibitors such as LY3321367, MG453 | The small molecular inhibitor | All of them have completed phase I clinical trials and have shown antitumor activity | Anti Tim3 drug tsr-022, Tim3 blocking antibody LY3321367, MG453 | Tim3 antibody has been clearly expressed to improve AML | |
| BiTE® BI 836909 [16–18] | Single-chain variable fragment (scFv) composed of anti-BCMA scFv at the N-terminal and anti-CD3ε scFv at the C-terminal, followed by hexahistidine | Animal experiment | 0.5, 0.05, 0.005 mg/kg per day for 26 days; median survival was 43.5 days (0.5 and 0.05 mg/kg per day) and 43 days (0.005 mg/kg per day), whereas the control group was 34 days | Neurotoxicity | In 2014, FDA approved for the treatment of Philadelphia chromosome-negative relapsed/refractory B-cell precursor acute lymphoblastic leukemia [6] |
| Blenrep | Joint: non cleavable MC; Payload: MMAF | The first stage NCT020 64387, DREAMM-1 [19, 20] | 4 mg/kg every 3 weeks ORR 60%; sCR 2 (6%), CR 3 (9%), VGPR 14 (40%); mPFS 12 months; mDOR 14.3 months | Grade 3 and 4 thrombocytopenia (35%), anemia (17%); hemocytopenia (52%); G1, 2 corneal events: blurred vision (52%), dry eyes (37%) | In early August 2020, it was approved in the United States for the treatment of relapsed or refractory MM in adult patients who have received at least four previous therapies, including anti-CD38 monoclonal antibody. In latter August 2020, Europe was also on trial |
| The second stage, NCT03525678, DREAMM-2 [21] | 2.5 or 3.4 mg/kg every 3 weeks; 2.5 mg/kg: ORR 30 (31%); sCR/CR 3 (3%), VGPR (15%); PD 56 (58%); mPFS 2.9 months; 3.4 mg/kg: ORR 34 (34%); sCR/CR 3 (3%), VGPR 17 (17%); PD 55 (56%); mPFS 4.9 months | Grade 3 and 4 keratopathy (27% in 2.5 mg/kg, 21% in 3.4 mg/kg), thrombocytopenia (20% and 33%) and anemia (20% and 25%) | |||
| CAR-T: CT053 (NCT03716856, NCT03302403 and NCT03380039) [22] | It includes anti-BCMA human scFv, CD3 ζT cell activation domain, and 4-1BB costimulatory domain | Phase I clinical trial | CT053 was given once after fludarabine/cyclophosphamide treatment; the total remission rate was 87.5% and the complete remission rate was 70.8% | Hematological toxicity, including a 95.8% decrease in white blood cell count and 66.7% thrombocytopenia. One subject died of BM failure and neutropenia infection. There were 62.5% cytokine release syndrome and 12.5% neurotoxicity | FDA approved two anti-CD19 CAR-T cell products: Yescarta and Kymriah used to treat patients with recurrent and/or refractory NH [23], Kymriah was initially approved in the USA for relapsed or refractory pediatric or young adult B-cell precursor acute lymphoblastic leukemia in 2017, and subsequently approved for adults with relapsed or refractory diffuse large B-cell lymphoma in early 2018 [24] |
AML: acute myeloid leukemia; sCR: stringent complete response; CR: complete response; VGPR: very good partial response; mPFS: median PFS; mDOR: median duration of response; MMAF: monomethyl auristatin F; MC: maleimidoca-proyl; DREAMM: the human study with belantamab mafodotin in patients with relapsed/refractory multiple myeloma; NH: non-Hodgkin lymphoma
