Management of patients with non-Hodgkin’s lymphoma: focus on adoptive T-cell therapy

Figures & data

Figure 1 T-cell-based approaches currently available to target NHL.

Abbreviations: NHL, non-Hodgkin’s lymphoma; CAR, chimeric antigen receptor; EBV, Epstein–Barr virus; TAA, tumor-associated antigen; CTA, cancer testis antigen; CTLs, cytotoxic T-cells.

Table 1 Reported clinical trials for NHL patients

	Trial*	Number of NHL patients reported and status	Type of NHL	Disease status pre-T-cell infusion	Outcome
LMP-2 CTLs^Citation16	NCT00062868 NCT00070226	8 and recruiting	1 CAeBv, 4 NK/T, 2 DLBCL, 1 anaplastic large cell lymphoma	5 patients treated in CR 3 patients with disease	4 CCR (8 weeks to +37 months); 1 NR 1 PR >36 months; 2 CR (9 and 10 months)
LMP1/2 CTLs^Citation15	NCT00671164	23 and recruiting	11 NK/T, 2 CAeBv, 7 DLBCL, 2 LYG, 1 peripheral T-cell lymphoma	11 patients treated in CR 12 patients with disease	9 CCR (from 2 years to +6 years); 1 relapsed; 1 NE 6 CR (from 2 years to +6 years); 1 PR‡ CR; 1 PR; 4 NR, relapsed (from 9 months to +4 years)
CAR CD19-28^Citation43	NCT00586391	6 and recruiting	1 SLL, 5 DLBCL	All patients with disease	2 SD (3 and 10 months); 4 PD
CAR CD19-28^Citation44,Citation45	NCT00924326	5 and recruiting	4 FL, 1 splenic marginal zone lymphoma	All patients with disease	1 NE (died from flu); 4 PR (from 7 months to +18 months)
CAR CD19^Citation46	NCT01087294	6 and recruiting	2 DLBCL, 4 MCL	All patients with disease	1 PR +3 months; 5 SD (from 1 month to +11 months)
CAR CD20-28-41BB^Citation28	NCT00621452	3 and recruiting	2 MCL, 1 FL	2 CR 1 SD	2 CCR +2 years PD +1 year
CAR CD20^Citation47	NCT00012207	7 completed	6 FL, 1 MCL	2 CR 2 SD, 3 PR	2 CCR (3 and 13 months) 4 SD (from 3 months to 12 months); 1 PR 3 months
CD20/CD19^Citation48	BB-IND-8513 BB-IND-11411	4 completed	2 FL, 2 DLBCL	NA	1 CR (after auto-SCT); 3 PD
CARκ	NCT00881920	5 and recruiting	2 DLBCL; 2 SLL; 1 FL	All patients with disease	2 CR; 1 PR; 2 PD

Note:

* Registered on ClinicalTrials.gov or US Food and Drug Administration-approved.

‡ Individual with PR went into CR.

Abbreviations: NHL, non-Hodgkin’s lymphoma; CTLs, cytotoxic T-cells; CAEBV, chronic active Epstein–Barr virus; NK/T, natural killer/T-cell NHL; DLBCL, diffuse large B-cell lymphoma; LYG, lymphoid granulomatosis; SLL, small lymphocytic lymphoma; FL, follicular lymphoma; MCL, mantle-cell lymphoma; CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease; auto-SCT, autologous stem cell transplant; CCR, continued complete response; NE, not evaluable; NR, no response.

Table 2 Other registered adoptive immunotherapy studies for NHL patients

Type of therapy	Trial	Status	Sponsor
Autologous CAR CD19-28ζ T-cells	NCT00586391	Recruiting	Baylor College of Medicine
Autologous or allogeneic multivirus-specific CAR CD19 T-cells	NCT00840853	Recruiting	Baylor College of Medicine
Autologous or allogeneic CAR CD19-28 T-cells versus CAR	NCT01853631	Recruiting	Baylor College of Medicine
CD19-28-4BB T-cells
Allogeneic CAR CD19-28 T-cells	NCT02050347	Not yet opened	Baylor College of Medicine
Autologous CAR CD19-TCRζ-41BB T-cells	NCT01626495	Recruiting	Children’s Hospital of Philadelphia
Autologous or allogeneic CAR CD19 T-cells	NCT01864889	Recruiting	Chinese PLA General Hospital
Autologous CD19-28-41BBζ T-cells	NCT02081937	Recruiting	Chinese PLA General Hospital
Autologous CAR CD19 CD28ζ/ΔEGFR, enriched Tcm	NCT01815749	Recruiting	City of Hope Medical Center
Autologous CAR CD19-2-28ζ/ΔEGFR, enriched Tcm	NCT02051257	Recruiting	City of Hope Medical Center
Allogeneic CMV-specific Tcm-derived CAR CD19 T-cells	NCT01475058	Recruiting	Fred Hutchinson Cancer Research Center
Autologous CAR CD19 T-cells	NCT01865617	Recruiting	Fred Hutchinson Cancer Research Center
Allogeneic EBV-specific CAR CD19 T-cells	NCT1430390	Recruiting	Memorial Sloan Kettering Cancer Center
Autologous CAR CD19-28ζ T-cells	NCT00924326	Recruiting	National Cancer Institute
Autologous CAR CD19 T-cells	NCT01593696	Recruiting	National Cancer Institute
Autologous CAR CD20 T-cells	NCT01735604	Recruiting	Chinese PLA General Hospital
Autologous CAR CD30 T-cells	NCT01316146	Recruiting	Baylor College of Medicine
Autologous CARκ T-cells	NCT00881920	Recruiting	Baylor College of Medicine
LMP1/2-specific CTLs	NCT00062868	Recruiting	Baylor College of Medicine
TGFβ-resistant LMP2-specific CTLs	NCT00368082	Recruiting	Baylor College of Medicine
EBV-specific CAR CD30 T-cells	NCT01192464	Recruiting	Baylor College of Medicine
Third-party LMP1/2-specific CTLs	NCT01447056	Recruiting	Baylor College of Medicine
EBNA-1, LMP1/2, BARF-1 peptide-specific EBV CTLs	NCT01555892	Recruiting	Baylor College of Medicine
Third-party LMP1/2-specific CTLs	NCT02057445	Recruiting	New York Medical College
Donor-derived LMP-specific CTLs post-allogeneic SCT	NCT01636388	Recruiting	New York Medical College
LMP1/2-specific CTLs	NCT01956084	Not yet opened	NA
Tumor-associated antigen-specific CTLs	NCT01333046	Recruiting	Baylor College of Medicine
NY-ESO-1 TCR-transgenic	NCT01697527	Recruiting	Jonsson Comprehensive Cancer Center

Abbreviations: NHL, non-Hodgkin’s lymphoma; CAR, chimeric antigen receptor; Tcm, central memory T cell; CMV, cytomegalovirus; EBV, Epstein–Barr virus; CTLs, cytotoxic T-cells; SCT, stem cell transplant; TCR, T-cell receptor; NA, not applicable.

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