An overview of preliminary clinical data from selected venetoclax-based trials
| Indication . | Intervention . | ORR, % . | CR, % . | MRD negativity . | Common grade 3-4 AEs (>10% of pts) and selected SAEs . | Trial . | Reference . |
|---|---|---|---|---|---|---|---|
| Cohort . | |||||||
| CLL | |||||||
| R/R CLL (n = 116) | VEN | 79 | 20 | 35% of CRs (BM, data from 17 out of 23 CRs) | Neutropenia (41%); anemia (12%); thrombocytopenia (12%) | NCT01328626 | 62 |
| R/R CLL with del17p (n = 107) | VEN | 79.4 | 8 | 40% (PB), (only 45/107 pts analyzed) | Neutropenia (40%); infections (20%) Anemia (18%); thrombocytopenia (15%) | NCT01889186 | 65 |
| R/R during or after Ibr treatment (n = 91) | VEN | 65 | 9 | 42% (PB, 57 pts evaluated) | Neutropenia (51%); anemia (29%); thrombocytopenia (29%); decreased WBC (19%); decreased lymphocyte count (15%); febrile neutropenia (13%) | NCT02141282 | 154,155 |
| R/R during or after idela treatment (n = 36) | 67 | 8* | 40% (PB) | Neutropenia (50%); thrombocytopenia (25%); Anemia (17%); hypokalemia (11%) | |||
| R/R CLL (n = 49) | VR | 86 | 51 | 57% (BM) | Neutropenia (53%); thrombocytopenia (16%); infections and infestations (16%); anemia (14%); febrile neutropenia (12%); leukopenia (12%); clinical TLS (4.1%, 1 death) | NCT01682616 | 66 |
| R/R CLL (n = 389) | VR vs BR | NCT02005471 (MURANO study) | 67 | ||||
| VR arm (n = 194) | 93.3 | 26.8 | 62.4% (PB) | Neutropenia (57.7%); infections and infestations (17.5%); anemia (10.8%); laboratory TLS (3.1%) | |||
| BR arm (n = 195) | 67.7 | 8.2 | 13.3% (PB) | Neutropenia (38.8%); infections and infestations (21.8%); anemia (13.8); thrombocytopenia (10.1%); laboratory TLS (1.1%) | |||
| TN CLL (n = 32) | VEN + G | 100 | 56 | 74% (BM, data from 27 out of 32 pts), 83% (PB) | Neutropenia (41%); febrile neutropenia (12.5%); anemia (12.5%); thrombocytopenia (12.5%) | NCT01685892 (GP28331 study) | 68 |
| TN CLL (n = 13) | VEN + G (study of VEN + G vs Chl + G) | 100 | 58 | 92% (PB) | Neutropenia (58.3%); febrile neutropenia (25%); infections (16.7%); laboratory TLS (16.7%) | NCT02242942 (CLL14) | 69 |
| TN CLL (n = 25) | VEN +Ibr. + G | 100 | 50* | 58% (BM+PB) | Neutropenia (44%); leukopenia (36%); thrombocytopenia (36%); lymphopenia (32%); hypertension (20%) | NCT02427451 | 74 |
| RR CLL (n = 50) 25 evaluated | VEN + Ibr | 100 | 60* | 28% (BM) | Neutropenia (46%); infections (12%); 2 pts had laboratory TLS | CLARITY | 72 |
| R/R CLL (n = 33), 14 evaluated | VEN + Ibr | 64.3 | — | All pts: neutropenia; 11% atrial fibrillation; 1 pt had laboratory TLS | NCT02756897 | 73 | |
| TN + high risk feature CLL (n = 39) 16 evaluated | 56.3 | — | |||||
| R/R and TN CLL (n = 55) | VEN + BR | NCT01671904 (GO28440) | 156 | ||||
| TN (n = 17) | 100 | 43* | 67% (BM) | Neutropenia (71%); anemia (29%); thrombocytopenia (24%); febrile neutropenia (12%) | |||
| RR (n = 30) | 96 | 26* | 76% (BM) | Neutropenia (63%); thrombocytopenia (27%); infections (27%); anemia (20%, diarrhea (10%) | |||
| VEN + BG | |||||||
| TN (n = 8) | 100 | 43* | 50% (BM) | Thrombocytopenia (63%); neutropenia (25%); fatigue (13%); IRR (13%) | |||
| NHL | |||||||
| All patients (n = 106) | VEN | 44 | 13 | All pts and at all doses: | NCT01328626 | 75 | |
| R/R WM (n = 4) | 100 | 0 | — | Anemia (15%); neutropenia (11%) | |||
| R/R MCL (n = 28) | 75 | 21 | — | ||||
| R/R MZL (n = 3) | 67 | 0 | — | ||||
| R/R RT (n = 7) | 43 | 0 | — | ||||
| R/R FL (n = 29) | 38 | 14 | — | ||||
| R/R DLBCL (n = 34) | 18 | 12 | — | ||||
| All patients (n = 60) | VEN + BR | 65 | 28.3 | — | All pts: neutropenia (60%); lymphopenia (38%); 24 patients reported SAEs; most frequent being febrile neutropenia and disease progression (8%). | NCT01594229 | 78 |
| (incl. DLBCL) | |||||||
| MZL (n = 6) | 100 | 50 | — | ||||
| FL (n = 32) | 75 | 34.4 | — | ||||
| R/R FL (n = 164) (160 evaluated of which 9 was a safety run-in) | VR vs VEN + BR vs BR | NCT02187861 | 157 | ||||
| VR (n = 52) | 33 | 14 | — | Neutropenia (27%); | |||
| VEN + BR (n = 49) | 68 | 50 | — | Neutropenia (59%); thrombocytopenia (39%); febrile neutropenia (10%) | |||
| BR (n = 50) | 64 | 41 | — | Neutropenia (24%) | |||
| MCL (n = 24) | VEN +Ibr | 71 | 62 | 93% of CRs (BM) | Neutropenia (33%); thrombocytopenia (17%); anemia (12%); diarrhea (12%); laboratory TLS in 2 pts | NCT02471391 | 79 |
| R/R (n = 23) | |||||||
| TN (n = 1) | |||||||
| R/R and TN NHL (FL, DLBCL, MZL, WM and others) (n = 56, 91% were TN) | VEN + R-CHOP | 86 | 66.7 | — | All pts: neutropenia (46%); febrile neutropenia (29%); thrombocytopenia (21%). 3 pts. had laboratory TLS | NCT02055820 | 80 |
| VEN + G-CHOP | 81 | 61.9 | — | ||||
| MM | |||||||
| R/R MM (n = 48), 43 evaluated | VEN | All pts: thrombocytopenia (29%); anemia (17%); neutropenia (17%) | NCT01794520 | 81 | |||
| All pts | 12 | 5% (7% VGPR) | — | ||||
| With t(11:14) (n = 17) | 24 | 12%, (12% VGPR) | — | ||||
| Without t(11:14) (n = 26) | 4 | 0% (4%VGPR) | — | ||||
| t(11:14) R/R MM (n = 20) | VEN + DEXA | All pts: 35% VGPR | All pts: lymphopenia (15%); hypophosphatemia (15%); hyperuricemia (10%); laboratory TLS (10%) | NCT01794520 | 83 | ||
| All pts | 65 | — | |||||
| Bortezomib refractory | 82 | — | |||||
| Lenalidomide refractory | 71 | — | |||||
| R/R MM (n = 66) | VEN + DEXA + bortezomib | All pts: (43% VGPR or better) | All pts: thrombocytopenia (29%); anemia (15%); neutropenia (14%) | NCT01794507 | 85 | ||
| All pts | 67 | — | |||||
| Bortezomib nonrefractory | 90 | — | |||||
| 1-3 prior treatments | 89 | — | |||||
| AML | |||||||
| R/R + TN AML | VEN | All pts: febrile neutropenia (31%); hypokalemia (22%); pneumonia (19%); hypotension (13%); urinary tract infection (13%) | NCT01994837 | 87 | |||
| All pts (n = 32) | 38† | 19 | — | ||||
| IDH1/2 mut (n = 12) | 50† | 33 | — | ||||
| TN AML (>65 y) | All groups (n = 57) | All pts: thrombocytopenia (47%); febrile neutropenia (42%); neutropenia (40%). Most frequent SAEs in group A and B were febrile neutropenia (30%, 32%); in group C lung infection (33%) | NCT02203773 | 92 | |||
| Group A: | VEN + decitabine (n = 23) | 65 | 61* | — | |||
| Group B: | VEN + azacitidine (n = 22) | 59 | 59* | — | |||
| Group C: | VEN + decitabine + posaconazole (n = 12) | 67 | 67* | — | |||
| TN AML (>65 y) (n = 71, 61 evaluated) | VEN + low dose cytarabine | 62* | — | NCT02287233 | 93 | ||
| VEN 600 mg (n = 61) | Thrombocytopenia (59%); neutropenia (46%); febrile neutropenia (36%); anemia (28%); decreased WBC count (26%); 1 case of TLS | ||||||
| Serious SAEs: febrile neutropenia (20%); malignant neoplasm progression (13%); pneumonia (13%) | |||||||
| R/R AML (>60 y) (n = 42) | VEN + Cobimetinib (n = 22) | 18 | 18* | — | Febrile neutropenia (23%); diarrhea (36%) | NCT02670044 | 96 |
| VEN + Idasanutlin (n = 20) | 20 | 15* | — | Febrile neutropenia (30%); decreased appetite (15%); diarrhea (10%); fatigue (10%); hypokalemia (10%) |
| Indication . | Intervention . | ORR, % . | CR, % . | MRD negativity . | Common grade 3-4 AEs (>10% of pts) and selected SAEs . | Trial . | Reference . |
|---|---|---|---|---|---|---|---|
| Cohort . | |||||||
| CLL | |||||||
| R/R CLL (n = 116) | VEN | 79 | 20 | 35% of CRs (BM, data from 17 out of 23 CRs) | Neutropenia (41%); anemia (12%); thrombocytopenia (12%) | NCT01328626 | 62 |
| R/R CLL with del17p (n = 107) | VEN | 79.4 | 8 | 40% (PB), (only 45/107 pts analyzed) | Neutropenia (40%); infections (20%) Anemia (18%); thrombocytopenia (15%) | NCT01889186 | 65 |
| R/R during or after Ibr treatment (n = 91) | VEN | 65 | 9 | 42% (PB, 57 pts evaluated) | Neutropenia (51%); anemia (29%); thrombocytopenia (29%); decreased WBC (19%); decreased lymphocyte count (15%); febrile neutropenia (13%) | NCT02141282 | 154,155 |
| R/R during or after idela treatment (n = 36) | 67 | 8* | 40% (PB) | Neutropenia (50%); thrombocytopenia (25%); Anemia (17%); hypokalemia (11%) | |||
| R/R CLL (n = 49) | VR | 86 | 51 | 57% (BM) | Neutropenia (53%); thrombocytopenia (16%); infections and infestations (16%); anemia (14%); febrile neutropenia (12%); leukopenia (12%); clinical TLS (4.1%, 1 death) | NCT01682616 | 66 |
| R/R CLL (n = 389) | VR vs BR | NCT02005471 (MURANO study) | 67 | ||||
| VR arm (n = 194) | 93.3 | 26.8 | 62.4% (PB) | Neutropenia (57.7%); infections and infestations (17.5%); anemia (10.8%); laboratory TLS (3.1%) | |||
| BR arm (n = 195) | 67.7 | 8.2 | 13.3% (PB) | Neutropenia (38.8%); infections and infestations (21.8%); anemia (13.8); thrombocytopenia (10.1%); laboratory TLS (1.1%) | |||
| TN CLL (n = 32) | VEN + G | 100 | 56 | 74% (BM, data from 27 out of 32 pts), 83% (PB) | Neutropenia (41%); febrile neutropenia (12.5%); anemia (12.5%); thrombocytopenia (12.5%) | NCT01685892 (GP28331 study) | 68 |
| TN CLL (n = 13) | VEN + G (study of VEN + G vs Chl + G) | 100 | 58 | 92% (PB) | Neutropenia (58.3%); febrile neutropenia (25%); infections (16.7%); laboratory TLS (16.7%) | NCT02242942 (CLL14) | 69 |
| TN CLL (n = 25) | VEN +Ibr. + G | 100 | 50* | 58% (BM+PB) | Neutropenia (44%); leukopenia (36%); thrombocytopenia (36%); lymphopenia (32%); hypertension (20%) | NCT02427451 | 74 |
| RR CLL (n = 50) 25 evaluated | VEN + Ibr | 100 | 60* | 28% (BM) | Neutropenia (46%); infections (12%); 2 pts had laboratory TLS | CLARITY | 72 |
| R/R CLL (n = 33), 14 evaluated | VEN + Ibr | 64.3 | — | All pts: neutropenia; 11% atrial fibrillation; 1 pt had laboratory TLS | NCT02756897 | 73 | |
| TN + high risk feature CLL (n = 39) 16 evaluated | 56.3 | — | |||||
| R/R and TN CLL (n = 55) | VEN + BR | NCT01671904 (GO28440) | 156 | ||||
| TN (n = 17) | 100 | 43* | 67% (BM) | Neutropenia (71%); anemia (29%); thrombocytopenia (24%); febrile neutropenia (12%) | |||
| RR (n = 30) | 96 | 26* | 76% (BM) | Neutropenia (63%); thrombocytopenia (27%); infections (27%); anemia (20%, diarrhea (10%) | |||
| VEN + BG | |||||||
| TN (n = 8) | 100 | 43* | 50% (BM) | Thrombocytopenia (63%); neutropenia (25%); fatigue (13%); IRR (13%) | |||
| NHL | |||||||
| All patients (n = 106) | VEN | 44 | 13 | All pts and at all doses: | NCT01328626 | 75 | |
| R/R WM (n = 4) | 100 | 0 | — | Anemia (15%); neutropenia (11%) | |||
| R/R MCL (n = 28) | 75 | 21 | — | ||||
| R/R MZL (n = 3) | 67 | 0 | — | ||||
| R/R RT (n = 7) | 43 | 0 | — | ||||
| R/R FL (n = 29) | 38 | 14 | — | ||||
| R/R DLBCL (n = 34) | 18 | 12 | — | ||||
| All patients (n = 60) | VEN + BR | 65 | 28.3 | — | All pts: neutropenia (60%); lymphopenia (38%); 24 patients reported SAEs; most frequent being febrile neutropenia and disease progression (8%). | NCT01594229 | 78 |
| (incl. DLBCL) | |||||||
| MZL (n = 6) | 100 | 50 | — | ||||
| FL (n = 32) | 75 | 34.4 | — | ||||
| R/R FL (n = 164) (160 evaluated of which 9 was a safety run-in) | VR vs VEN + BR vs BR | NCT02187861 | 157 | ||||
| VR (n = 52) | 33 | 14 | — | Neutropenia (27%); | |||
| VEN + BR (n = 49) | 68 | 50 | — | Neutropenia (59%); thrombocytopenia (39%); febrile neutropenia (10%) | |||
| BR (n = 50) | 64 | 41 | — | Neutropenia (24%) | |||
| MCL (n = 24) | VEN +Ibr | 71 | 62 | 93% of CRs (BM) | Neutropenia (33%); thrombocytopenia (17%); anemia (12%); diarrhea (12%); laboratory TLS in 2 pts | NCT02471391 | 79 |
| R/R (n = 23) | |||||||
| TN (n = 1) | |||||||
| R/R and TN NHL (FL, DLBCL, MZL, WM and others) (n = 56, 91% were TN) | VEN + R-CHOP | 86 | 66.7 | — | All pts: neutropenia (46%); febrile neutropenia (29%); thrombocytopenia (21%). 3 pts. had laboratory TLS | NCT02055820 | 80 |
| VEN + G-CHOP | 81 | 61.9 | — | ||||
| MM | |||||||
| R/R MM (n = 48), 43 evaluated | VEN | All pts: thrombocytopenia (29%); anemia (17%); neutropenia (17%) | NCT01794520 | 81 | |||
| All pts | 12 | 5% (7% VGPR) | — | ||||
| With t(11:14) (n = 17) | 24 | 12%, (12% VGPR) | — | ||||
| Without t(11:14) (n = 26) | 4 | 0% (4%VGPR) | — | ||||
| t(11:14) R/R MM (n = 20) | VEN + DEXA | All pts: 35% VGPR | All pts: lymphopenia (15%); hypophosphatemia (15%); hyperuricemia (10%); laboratory TLS (10%) | NCT01794520 | 83 | ||
| All pts | 65 | — | |||||
| Bortezomib refractory | 82 | — | |||||
| Lenalidomide refractory | 71 | — | |||||
| R/R MM (n = 66) | VEN + DEXA + bortezomib | All pts: (43% VGPR or better) | All pts: thrombocytopenia (29%); anemia (15%); neutropenia (14%) | NCT01794507 | 85 | ||
| All pts | 67 | — | |||||
| Bortezomib nonrefractory | 90 | — | |||||
| 1-3 prior treatments | 89 | — | |||||
| AML | |||||||
| R/R + TN AML | VEN | All pts: febrile neutropenia (31%); hypokalemia (22%); pneumonia (19%); hypotension (13%); urinary tract infection (13%) | NCT01994837 | 87 | |||
| All pts (n = 32) | 38† | 19 | — | ||||
| IDH1/2 mut (n = 12) | 50† | 33 | — | ||||
| TN AML (>65 y) | All groups (n = 57) | All pts: thrombocytopenia (47%); febrile neutropenia (42%); neutropenia (40%). Most frequent SAEs in group A and B were febrile neutropenia (30%, 32%); in group C lung infection (33%) | NCT02203773 | 92 | |||
| Group A: | VEN + decitabine (n = 23) | 65 | 61* | — | |||
| Group B: | VEN + azacitidine (n = 22) | 59 | 59* | — | |||
| Group C: | VEN + decitabine + posaconazole (n = 12) | 67 | 67* | — | |||
| TN AML (>65 y) (n = 71, 61 evaluated) | VEN + low dose cytarabine | 62* | — | NCT02287233 | 93 | ||
| VEN 600 mg (n = 61) | Thrombocytopenia (59%); neutropenia (46%); febrile neutropenia (36%); anemia (28%); decreased WBC count (26%); 1 case of TLS | ||||||
| Serious SAEs: febrile neutropenia (20%); malignant neoplasm progression (13%); pneumonia (13%) | |||||||
| R/R AML (>60 y) (n = 42) | VEN + Cobimetinib (n = 22) | 18 | 18* | — | Febrile neutropenia (23%); diarrhea (36%) | NCT02670044 | 96 |
| VEN + Idasanutlin (n = 20) | 20 | 15* | — | Febrile neutropenia (30%); decreased appetite (15%); diarrhea (10%); fatigue (10%); hypokalemia (10%) |
AE, adverse event; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; BG, bendamustine + obinutuzumab; BM, bone marrow; BR, bendamustine + rituximab; Chl, chlorambucil; CLL, chronic lymphocytic leukemia; CR, complete response; DEXA, dexamethasone; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; Ibr, ibrutinib; idela, idelalisib; G, obinutuzumab; MCL, mantle cell lymphoma; MRD, minimal residual disease; MZL, marginal zone lymphoma; PB, peripheral blood; PR, partial response; pts, patients; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone; R/R, relapsed/refractory; RT, Richter transformation; R, rituximab; SAEs, severe adverse events; TLS, tumor lysis syndrome; TN, treatment naïve; VEN, venetoclax; VGPR, very good partial response; VR, venetoclax + rituximab; WM, Waldenstrom macroglobulinemia.
CR/CRi/CRp.
Overall activity (objective responses by IWG criteria and antileukemic activity not meeting IWG criteria).