Table 2.
Selected clinical trials of CAR T cells in B-cell non-Hodgkin lymphomas and chronic lymphocytic leukemia.
| Setting | Target | Product | Costimul. domain | Generation | Vector | Population infused | Response | Durable remission rate | CRS (gr.3/4) | NTX (gr.3/4) | Institute/Company | Clinical trial | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| B-cell NHL | CD19 | Axicabtagene ciloleucel (KTE-C19, Yescarta®) |
CD28 | Second (2nd) | Retroviral | 108, R/R DLBCL, PMBCL, t-FL |
ORR 83% CR 58% |
Median DOR 11.1 mo |
11%§ | 32%± | NCI/Kite, Gilead | ZUMA-1 NCT02348216 multicenter phase I/II |
(25) |
| KTE-X19 | 68, R/R MCL | ORR 93% CR 67% |
Unknown | 15%§ | 31%± | ZUMA-2 NCT02601313 multicenter phase II |
(29) | ||||||
| Tisagenlecleucel (CTL019, Kymriah®) | 4-1BB | Second (2nd) | Lentiviral | 111, R/R DLBCL, t- FL |
ORR 52% CR 40% |
12-mo RFS 65% | 22%¥ | 12%± | UPenn/Novartis | JULIET NCT02445248 Multicenter phase IIa |
(26) | ||
| Lisocabtagene maraleucel (JCAR017) | 4-1BB | Second (2nd) | Lentiviral | 269, R/R DLBCL, t-FL, PMBCL, FL3B, HGBCL |
ORR 73% CR 53% |
12-mo DOR 54.7% |
2%§ | 10%± | FHCRC/Juno, Celgene | TRANSCEND-001 NCT02631044 Multicenter phase I |
(28) | ||
| Lisocabtagene maraleucel (JCAR017) + Durvalumab |
4-1BB | Second (2nd) | Lentiviral | 11, R/R B-NHL | ORR 91% CR 64% |
Unknown | Unknown | Unknown | Celgene/Juno | PLATFORM NCT03310619 Phase I/II |
(46) | ||
| JCAR014 + Durvalumab | 4-1BB | Second (2nd) | Lentiviral | 15, R/R Aggressive B-NHL |
ORR 50% | Ongoing remission 33% | 7%§ | 0%± | FHCRC/Juno, MedImmune |
NCT02706405 Phase Ib |
(47) | ||
| CD20 | CD20-CAR | None | First (1st) | Plasmidic | 7, R/R Indolent NHL, MCL |
ORR 43% CR 28% |
Median DOR 5 mo |
0%° | 0%° | FHCRC |
NCT00012207 Phase I |
(48) | |
| scFvFc.CD28-CD137z | CD28 4-1BB | Third (3rd) | Plasmidic | 3, R/R indolent NHL, MCL |
ORR 100% CR 67% PR 33% |
Unknown | 0%° | 0%° | FHCRC |
NCT00621452 Phase I |
(49) | ||
| CLL | CD19 | Tisagenlecleucel (CTL019, Kymriah®) | 4-1BB | Second (2nd) | Lentiviral | 14, R/R CLL/SLL | ORR 57% CR 29% |
Unknown | 43%¥ | 7%° | UPenn/Novartis |
NCT01029366 Phase I |
(14) |
| Lisocabtagene maraleucel (JCAR017) | 4-1BB | Second (2nd) | Lentiviral | 23, R/R CLL/SLL | ORR 81% CR 45% |
Unknown | 9%§ | 22%± | Juno, Celgene | TRANSCEND-CLL-004 NCT03331198 Phase I/II |
(50) | ||
| CTL119.BBz-CAR + Ibrutinib | 4-1BB | Second (2nd) | Lentiviral | 19, r/r cll | ORR 71% CR 43% |
Ongoing remission 53% at 12 mo (MRD− 37%) | 16%¥ | 5%± | UPenn |
NCT02640209 Pilot trial |
(51) | ||
| CD19-BBz.EGFRt-CAR | 4-1BB | Second (2nd) | Lentiviral | 24, r/r cll Post-ibrutinib (5 richter, 25% post -venetoclax) |
ORR 71% CR 21% MRD neg 58% |
Unknown | 25%§ | 25%± | FHCRC |
NCT01865617 Phase I/II |
(52) |
, Penn/CHOP grading scale;
, NCI 2014 consensus grading scale modified by Lee DW et al. (45);
, CTCAE v3.0;
, CTCAE v4.03.
NHL, non-Hodgkin lymphoma; DLBCL, diffuse large B-cell lymphoma; t-FL, transformed follicular lymphoma; FL3B, grade 3B follicular lymphoma; MCL, mantle cell lymphoma; PMBCL, primary mediastinal B-cell lymphoma; HGBCL, high-grade B-cell lymphoma; CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; R/R, relapse/refractory; ORR, overall response rate; CR, complete remission; PR, partial response; MRD, minimal residual disease; DOR, duration of response; OS, overall survival; PFS, progression-free survival; RFS, relapse-free survival; CRS, cytokine release syndrome; NTX, neurotoxicity; UPenn, University of Pennsylvania Hospital; FHCRC, Fred Hutchinson Cancer Research Center; NCI, National Cancer Institute.