Efficacy and safety of 2-drug combination therapies in R/R PTCL and CTCL
| Drug combination . | Drug targets . | Trial phase . | Enrolled patients with TCL (n) . | Previous treatment lines, median (range) . | Patients evaluated (n) . | ORR (%) . | CRR (%) . | OS, median (mo) . | PFS, median (mo) . | DoR, median (mo) . | Most prevalent gr 3-4 AEs . | AEs, n (%) . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Romi + azacitidine∗ | HDAC + DNMT1 | Real-world | Overall: 27† | 1 (0-5) | Overall: 26 | 76.9 | 53 | NR | 7.07 | NR | Thrombocytopenia‡ | 14 (51) | 8 |
| AITL: 19 | AITL + TFH: 23 | 69.5 | 60.8 | Nausea‡ | 11 (40) | ||||||||
| TFH: 3 | Neutropenia‡ | 10 (37) | |||||||||||
| PTCL-NOS: 1 | Fatigue‡ | 8 (29) | |||||||||||
| ATLL: 2 | Anemia‡ | 6 (22) | |||||||||||
| TFH-PTCL + DLBCL: 1 | |||||||||||||
| ALK– ALCL + FL: 1 | |||||||||||||
| Romi + azacitidine† | HDAC + DNMT1 | 2 | Overall: 14 | 2 (1-6) | Overall: 13 | 54 | 38 | 20.6 | 8.0 | 13.5 | Thrombocytopenia | 12 (48) | 9 |
| AITL: 9 | Neutropenia | 10 (40) | |||||||||||
| PTCL-NOS: 2 | Lymphopenia | 8 (32) | |||||||||||
| ALCL: 1: | Anemia | 4 (16) | |||||||||||
| EATL: 1 | Febrile neutropenia | 3 (12) | |||||||||||
| ENKTCL: 1 | |||||||||||||
| Romi + azacitidine§ | HDAC + DNMT1 | 1 | Overall: 11 | 6 (1-15) | Overall: 11 | 73 | 55 | — | NR | — | Lymphopenia | 11 (42) | 10 |
| AITL: 3 | Neutropenia | 11 (42) | |||||||||||
| PTCL-NOS: 2 | Thrombocytopenia | 7 (27) | |||||||||||
| ATLL: 2 | Leukopenia | 6 (23) | |||||||||||
| ALCL: 1 | Anemia | 5 (19) | |||||||||||
| CTCL: 1 | |||||||||||||
| EATL: 1 | |||||||||||||
| ENKTCL: 1 | |||||||||||||
| Romi + lenalidomide|| | HDAC + E3 ubiquitin | 2 | Overall: 27 | 3 (1-12) | Overall: 24 | 50 | 13 | 18.3 | 4.8 | 15.7 | Thrombocytopenia | 26 (53) | 11 |
| AITL: 3 | PTCL: 15 | 53 | 13 | Lymphopenia | 25 (51) | ||||||||
| PTCL-NOS: 5 | CTCL: 9 | 44 | 11 | Neutropenia | 24 (49) | ||||||||
| ATLL: 7 | Leukopenia | 22 (45) | |||||||||||
| ENKTCL: 1 | Anemia | 13 (27) | |||||||||||
| T-PLL: 1 | |||||||||||||
| CTCL, MF: 7 | |||||||||||||
| CTCL-SS: 3 | |||||||||||||
| Romi + pembrolizumab | HDAC + PD1 | 2 | Overall: 38 | 2 (1-6) | Overall: 38 | 47.3 | 37.3 | 21.3 | — | — | Infection, NOS‡,¶ | 11 (28) | 12 |
| Thrombocytopenia | 10 (26) | ||||||||||||
| Romi + pralatrexate# | HDAC + DHFR | 2 | Overall: 18 | 2 (0-7) | Overall: 14 | 35.7 | 14.3 | 20.2 | 3.56 | 8.2 | Infection∗∗ | 4 (24) | 13 |
| PTCL-NOS: 8 | PTCL-NOS: 6 | 33 | Sepsis | 1 (6) | |||||||||
| PTCL with TFH phenotype/AITL: 4 | PTCL with TFH phenotype/AITL: 3 | 50 | Anemia | 1 (6) | |||||||||
| ATLL: 2 | ATLL: 2 | Heart failure | 1 (6) | ||||||||||
| ENKTCL: 1 | ENKTCL: 1 | Sinus tachycardia | 1 (6) | ||||||||||
| CTCL: 1 | CTCL: 1 | ||||||||||||
| Subcutaneous panniculitis PTCL: 2 | Subcutaneous panniculitis PTCL: 1 | ||||||||||||
| Duv + azacitidine | PI3K-δ + DNMT1 | 1 | Overall: 14 | 2 (1-21) | Overall: 14 | 46 | 31 | 10.2 | 2.2 | — | Neutropenia‡ | 4 (28) | 14 |
| TFH: 4 | TFH: 4 | 100 | 100 | Anemia‡ | 3 (21) | ||||||||
| CTCL: 2 | Transaminitis | 2 (14) | |||||||||||
| Thrombocytopenia‡ | 2 (14) | ||||||||||||
| Leukopenia‡ | 1 (7) | ||||||||||||
| Duv + ruxolitinib†† | PI3K-δ + JAK | 1 | Overall: 49 | ‡ | Overall: 49 | 41 | 24 | — | — | NR | Neutropenia | (38) | 15 |
| PTCL-NOS: 13 | PTCL-NOS: 13 | 23 | 15 | Anemia | (16) | ||||||||
| TFH: 14 | TFH: 14 | 79 | 64 | Thrombocytopenia | (12) | ||||||||
| T-PLL: 3 | T-PLL: 3 | 60 | 0 | Transaminitis | (4) | ||||||||
| T-LGL: 3 | T-LGL: 3 | 67 | 33 | Hypertension | (4) | ||||||||
| MF: 7 | MF: 7 | 14 | 0 | ||||||||||
| ATLL: 1 | |||||||||||||
| ALCL, ALK–: 3 | |||||||||||||
| ALCL, ALK+: 1 | |||||||||||||
| MEITL: 1 | |||||||||||||
| Durvalumab + lenalidomide | PD1 + E3 ubiquitin | 2 | Overall: 13 | 3‡‡ | Overall: 12 | 75 | — | — | NR | — | Neutropenia | 1 (8) | 16 |
| CTCL: 13 | CTCL: 12 | 75 | |||||||||||
| Chidamide + sintilimab | HDAC + PD1 | 1b/2 | Overall: 38 | 1 (1-2) | Overall: 37 | 59.5 | 48.6 | 32.9 | 23.2 | 25.3 | Neutropenia | 11 (29) | 17 |
| ENKTCL, phase 1b: 9 | ENKTCL, phase 1b: 9 | 66.7 | 55.6 | Leukopenia | 3 (8) | ||||||||
| ENKTCL, phase 2: 28 | ENKTCL, phase 2: 28 | 57.1 | 46.4 | Lymphopenia | 3 (8) | ||||||||
| Thrombocytopenia | 4 (11) | ||||||||||||
| Azacitidine + nivolumab | PD1 + DNMT1 | NA | Overall: 9 | 1 (1-2) | Overall: 9 | 78 | 33 | — | — | — | Neutropenia | 1 (11) | 18 |
| AITL: 9 | AITL: 9 | 78 | 33 | Anemia | 1 (11) | ||||||||
| Colitis | 1 (11) |
| Drug combination . | Drug targets . | Trial phase . | Enrolled patients with TCL (n) . | Previous treatment lines, median (range) . | Patients evaluated (n) . | ORR (%) . | CRR (%) . | OS, median (mo) . | PFS, median (mo) . | DoR, median (mo) . | Most prevalent gr 3-4 AEs . | AEs, n (%) . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Romi + azacitidine∗ | HDAC + DNMT1 | Real-world | Overall: 27† | 1 (0-5) | Overall: 26 | 76.9 | 53 | NR | 7.07 | NR | Thrombocytopenia‡ | 14 (51) | 8 |
| AITL: 19 | AITL + TFH: 23 | 69.5 | 60.8 | Nausea‡ | 11 (40) | ||||||||
| TFH: 3 | Neutropenia‡ | 10 (37) | |||||||||||
| PTCL-NOS: 1 | Fatigue‡ | 8 (29) | |||||||||||
| ATLL: 2 | Anemia‡ | 6 (22) | |||||||||||
| TFH-PTCL + DLBCL: 1 | |||||||||||||
| ALK– ALCL + FL: 1 | |||||||||||||
| Romi + azacitidine† | HDAC + DNMT1 | 2 | Overall: 14 | 2 (1-6) | Overall: 13 | 54 | 38 | 20.6 | 8.0 | 13.5 | Thrombocytopenia | 12 (48) | 9 |
| AITL: 9 | Neutropenia | 10 (40) | |||||||||||
| PTCL-NOS: 2 | Lymphopenia | 8 (32) | |||||||||||
| ALCL: 1: | Anemia | 4 (16) | |||||||||||
| EATL: 1 | Febrile neutropenia | 3 (12) | |||||||||||
| ENKTCL: 1 | |||||||||||||
| Romi + azacitidine§ | HDAC + DNMT1 | 1 | Overall: 11 | 6 (1-15) | Overall: 11 | 73 | 55 | — | NR | — | Lymphopenia | 11 (42) | 10 |
| AITL: 3 | Neutropenia | 11 (42) | |||||||||||
| PTCL-NOS: 2 | Thrombocytopenia | 7 (27) | |||||||||||
| ATLL: 2 | Leukopenia | 6 (23) | |||||||||||
| ALCL: 1 | Anemia | 5 (19) | |||||||||||
| CTCL: 1 | |||||||||||||
| EATL: 1 | |||||||||||||
| ENKTCL: 1 | |||||||||||||
| Romi + lenalidomide|| | HDAC + E3 ubiquitin | 2 | Overall: 27 | 3 (1-12) | Overall: 24 | 50 | 13 | 18.3 | 4.8 | 15.7 | Thrombocytopenia | 26 (53) | 11 |
| AITL: 3 | PTCL: 15 | 53 | 13 | Lymphopenia | 25 (51) | ||||||||
| PTCL-NOS: 5 | CTCL: 9 | 44 | 11 | Neutropenia | 24 (49) | ||||||||
| ATLL: 7 | Leukopenia | 22 (45) | |||||||||||
| ENKTCL: 1 | Anemia | 13 (27) | |||||||||||
| T-PLL: 1 | |||||||||||||
| CTCL, MF: 7 | |||||||||||||
| CTCL-SS: 3 | |||||||||||||
| Romi + pembrolizumab | HDAC + PD1 | 2 | Overall: 38 | 2 (1-6) | Overall: 38 | 47.3 | 37.3 | 21.3 | — | — | Infection, NOS‡,¶ | 11 (28) | 12 |
| Thrombocytopenia | 10 (26) | ||||||||||||
| Romi + pralatrexate# | HDAC + DHFR | 2 | Overall: 18 | 2 (0-7) | Overall: 14 | 35.7 | 14.3 | 20.2 | 3.56 | 8.2 | Infection∗∗ | 4 (24) | 13 |
| PTCL-NOS: 8 | PTCL-NOS: 6 | 33 | Sepsis | 1 (6) | |||||||||
| PTCL with TFH phenotype/AITL: 4 | PTCL with TFH phenotype/AITL: 3 | 50 | Anemia | 1 (6) | |||||||||
| ATLL: 2 | ATLL: 2 | Heart failure | 1 (6) | ||||||||||
| ENKTCL: 1 | ENKTCL: 1 | Sinus tachycardia | 1 (6) | ||||||||||
| CTCL: 1 | CTCL: 1 | ||||||||||||
| Subcutaneous panniculitis PTCL: 2 | Subcutaneous panniculitis PTCL: 1 | ||||||||||||
| Duv + azacitidine | PI3K-δ + DNMT1 | 1 | Overall: 14 | 2 (1-21) | Overall: 14 | 46 | 31 | 10.2 | 2.2 | — | Neutropenia‡ | 4 (28) | 14 |
| TFH: 4 | TFH: 4 | 100 | 100 | Anemia‡ | 3 (21) | ||||||||
| CTCL: 2 | Transaminitis | 2 (14) | |||||||||||
| Thrombocytopenia‡ | 2 (14) | ||||||||||||
| Leukopenia‡ | 1 (7) | ||||||||||||
| Duv + ruxolitinib†† | PI3K-δ + JAK | 1 | Overall: 49 | ‡ | Overall: 49 | 41 | 24 | — | — | NR | Neutropenia | (38) | 15 |
| PTCL-NOS: 13 | PTCL-NOS: 13 | 23 | 15 | Anemia | (16) | ||||||||
| TFH: 14 | TFH: 14 | 79 | 64 | Thrombocytopenia | (12) | ||||||||
| T-PLL: 3 | T-PLL: 3 | 60 | 0 | Transaminitis | (4) | ||||||||
| T-LGL: 3 | T-LGL: 3 | 67 | 33 | Hypertension | (4) | ||||||||
| MF: 7 | MF: 7 | 14 | 0 | ||||||||||
| ATLL: 1 | |||||||||||||
| ALCL, ALK–: 3 | |||||||||||||
| ALCL, ALK+: 1 | |||||||||||||
| MEITL: 1 | |||||||||||||
| Durvalumab + lenalidomide | PD1 + E3 ubiquitin | 2 | Overall: 13 | 3‡‡ | Overall: 12 | 75 | — | — | NR | — | Neutropenia | 1 (8) | 16 |
| CTCL: 13 | CTCL: 12 | 75 | |||||||||||
| Chidamide + sintilimab | HDAC + PD1 | 1b/2 | Overall: 38 | 1 (1-2) | Overall: 37 | 59.5 | 48.6 | 32.9 | 23.2 | 25.3 | Neutropenia | 11 (29) | 17 |
| ENKTCL, phase 1b: 9 | ENKTCL, phase 1b: 9 | 66.7 | 55.6 | Leukopenia | 3 (8) | ||||||||
| ENKTCL, phase 2: 28 | ENKTCL, phase 2: 28 | 57.1 | 46.4 | Lymphopenia | 3 (8) | ||||||||
| Thrombocytopenia | 4 (11) | ||||||||||||
| Azacitidine + nivolumab | PD1 + DNMT1 | NA | Overall: 9 | 1 (1-2) | Overall: 9 | 78 | 33 | — | — | — | Neutropenia | 1 (11) | 18 |
| AITL: 9 | AITL: 9 | 78 | 33 | Anemia | 1 (11) | ||||||||
| Colitis | 1 (11) |
ALK+, anaplastic lymphoma kinase–positive; DHFR, dihydrofolate reductase; DLBCL, diffuse large B-cell lymphoma; DNMT1, DNA methyltransferase 1; EATL, enteropathy-associated T-cell lymphoma; FL, follicular lymphoma; MEITL, monomorphic epitheliotropic intestinal T-cell lymphoma; NA, not applicable; PD1, programmed cell death protein 1; SS, Sézary syndrome; T-LGL, T-cell large granular lymphocytic leukemia; T-PLL, T-cell prolymphocytic leukemia.
Three (3/27) patients of unspecified histology were treatment-naive and included in all treatment response and AE measures. R/R-specific outcomes were not reported by the authors.
AE rates include treatment-naive patients.
Gr of AE not reported.
Median lines of therapy and AE rates include treatment-naive patients and those with Hodgkin and B-cell lymphomas.
Median lines of therapy and DoR include patients with R/R Hodgkin and B-cell lymphomas.
Infection type not reported.
Three (3/18) patients of unspecified histology were treatment-naive and included in all treatment response and AE measures. R/R-specific outcomes were not reported by the authors.
Gr 3 to 4 infection included staphylococcal infection, lymph node infection, and upper respiratory infection, and appendicitis.
Treatment response and AE measures include treatment-naive patients of unknown count.
Median lines of therapy included systemic therapies only (range not reported).