Table 4.
Selected reports of immunotherapy for natural killer/T cell lymphoma
| Targets | Intervention/treatment | Phase/Study design | Disease | Sample size | Dosing | Treatment | ORR (%) | CRR (%) | Common AE | Median follow-up, mo (range) | Trial identifier | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PD-1/PD-L1 | Pembrolizumab | Retrospective | Relapsed or refractory after SMILE-like therapy | 7 | 2 mg/kg every 3 weeks | Single agent | 100% | 71.40% | Grade 2 rush | 6 (2–10) | Kwong et al.59 | |
| Retrospective | Relapsed or refractory NKTCL | 7 | 100 mg every 3 weeks | Single agent | 57.10% | 28.6% | All-grade AEs 71.4% | NA | Li et al.28 | |||
| Retrospective | Relapsed or refractory NHL (include 14 NKTCL) | 30 | 100 mg or 200mg every 3 weeks | Single agent | NKTCL: 44% | – | Grade II skin rash, bowel perforation | NA | Kim et al.121 | |||
| Nivolumab | Retrospective | Relapsed or refractory after SMILE-like therapy | 3 | 40 mg (the smallest vial available) every 2 weeks | Single agent, low dose | 100.00% | 66.70% | NA | NA | Chan et al.29 | ||
| Sintilimab | Phase 2 | Relapsed or refractory ENKTL | 28 | 200mg every 3 weeks | Single agent | 75.0% | 21.4% | Decreased lymphocyte count (46.5%), pyrexia (42.9%), and decreased white blood cell count (35.7%) | 30.4 (27.5–31.9) | NCT03228836 | Tao et al.58 | |
| Avelumab | Phase 2 | Relapsed or refractory ENKTL | 21 | 10 mg/kg on days 1 and 15 of a 28-day cycle | Single agent | 38.0% | 24.0% | Fever (29%), anorexia (10%), Infusion-related reaction (19%) | 15.7 (95% CI: 14.5–16.9) | NCT03439501 | Kim et al.61 | |
| Sugemalimab | Phase 2 | Relapsed or refractory ENKTL | 80 | 1200 mg | Single agent | 45.6% | 30.4% | – | 18.7 | NCT03595657 | Huang et al.34 | |
| CCR4 | Mogamulizumab (KW-0761) | Phase 2 | CCR4-positive Peripheral T/NK-cell Lymphoma | 37 | 1.0 mg/kg once weekly for 8 weeks | Single agent | 35.0% | 14.0% | Lymphocytopenia (81%), neutropenia (38%), leukocytopenia (43%), and pyrexia (30%) | NA | NCT01192984 | Ogura et al.122 |
| Relapsed/refractory peripheral T cell lymphoma | 35 | 1.0 mg/kg once weekly for 4 weeks | Single agent | 11.40% | 3.00% | Drug eruption (34.2%), pyrexia (23.7%), diarrhea (18.4%), and pruritus (18.4%) | NA | – | Zinzani et al.123 | |||
| CD30 | Brentuximab vedotin | Phase 1 | Refractory or relapsed HL or CD30+ NHL | 24 | SGN-30 at 4 dose levels (2, 4, 8, or 12 mg/kg) weekly for 6 consecutive weeks | Single agent | Modest efficacy | 4.16% | Nausea (13.0%), fatigue (13.0%), and fever (13.0%) | NA | NCT00051597 | Bartlett et al.124 |
| Phase 1 | Relapsed or refractory CD30-positive hematologic cancers | 45 | 0.1 to 3.6 mg/kg every 3 weeks | Single agent | 67.0% | 24.4% | Fatigue (36%), pyrexia (33%), and diarrhea, nausea, neutropenia, and peripheral neuropathy (22% each) | NA | NCT00430846 | Younes et al.125 | ||
| Phase 2 | Relapsed/refractory CD30+ NHL | 34 | 1.8 mg/kg every 3 weeks | Single agent | 41.0% | 23.5% | Neutropenia (14%), peripheral sensory neuropathy, and hyperkalemia (9% each) | 2.7 (0.3–17.3) | NCT01421667 | Horwitz et al.126 | ||
| Cases | ENKTL with CD30 expression | 2 | 1.8 mg/kg every 3 weeks | Single-agent | – | – | Grade 2 toxicity dyspnea | – | – | Kim et al., Poon et al.89,90 | ||
| Phase 2 | Relapsed or Refractory EBV-and CD30-positive Lymphomas | 25 | 1.8 mg/kg every 3 weeks | Single-agent | 48.0% | 20.0% | Peripheral neuropathy (48%), neutropenia (44%), thrombocytopenia (20%), and rash (16%) | 20 (1.7–30.4) | NCT02388490 | Kim et al.41 | ||
| CD38 | Daratumumab | Phase 2 | Relapsed or refractory ENKTL | 32 | 16 mg/kg once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter, all cycles were 28 days | Single agent | 25.0% | – | Thrombocytopenia (25.0%), neutropenia (18.8%), and anemia and leukopenia (15.6%) | 10.2 months | NCT02927925 | Huang et al.45 |
| Case | A patient with stage IV NKTCL | 1 | 16 mg/kg weekly | Single agent | Patients reached a maximum sustained remission period of 21 weeks. | – | Multiple infectious complications (were considered unrelated to daratumumab) | NA | – | Hari et al.46 | ||
| CD52 | Alemtuzumab | Phase 2 | Newly diagnosed PTCL (inlude 3 ENKTL) | 3 | 10 mg i.v. on day 1 and 20 mg i.v. on day 2 in the Wrst cycle, then 30 mg i.v. on day 1 in the subsequent cycles | Combined with CHOP | 80.0% | 65.0% | Neutropenia (90%), febrile neutropenia (55.0%), cytomegalovirus reactivation (25%) | 7 (1–12) | – | Kim et al.99 |
| Phase 2 | Relapsed or refractory PTCL after first-line therapy | 8 | 70 mg or 40 mg | Combined with DHAP | 50.0% | 29.1% | Leukopenia (79.2%) | NA | – | Kim et al.48 | ||
| EBV antigens (LMP1/LMP2) | Activated/stimulated T cells | Phase 1 | EBV-associated lymphoma | 50 | 2 x 107-3 x 108 cells/m2 | LMP-Specific CTLs As Adjuvant Therapy | – | – | There were no clinical toxicities associated with the CTLs | NA | NCT00671164 | Bollard et al.107 |
| IMiDs | Thalidomide | Prospective, single center | T-NHL (include 21 NKTCL) | 46 | 200 mg (range, 150–400 mg) every night | Combined with chemotherapy | 79.2% | 50.0% | Without reported severe side effects | NA | – | Wu et al.,127 |
PD-1, programmed death 1; PD-L1, programmed cell death-ligand 1; C-C chemokine receptor 4; SMILE, dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide; DHAP, dexamethasone, cytarabine, and cisplatin; HL, Hodgkin lymphomas; NHL, non-Hodgkin lymphomas; NKTCL, natural killer/T cell lymphoma; ENKTL, extranodal NK/T-cell lymphoma; AEs, adverse events; CCR4, C-C chemokine receptor 4; PTCL, peripheral T cell lymphoma; IMiDs, immunomodulatory drugs; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; ORR, objective response rate; CRR, complete response rate; OS, overall survival; NE, not estimable; 95% CI, 95% confidence interval; NA, data not available.