Table 4.

Studies of venetoclax with or without anti-CD20 antibodies or chemotherapy in B-NHL

Study	Cohort	Design	ORR/CRR MRD	PFS/OS	III/IV toxicity (> 10%)	Note
Mantle cell lymphoma
Davids et al.[35, 38] NCT01328626	n = 28 R/R MCL (median 3 prior lines of therapy) Lenalidomide and ibrutinib naïve 18% bortezomib exposed	Phase 1 dose escalation venetoclax monotherapy 200-1200 mg daily	ORR 75% CRR 21%	Median PFS 11 months Median DOR 16 months 12-month OS: 82%	Overall cohort Anemia 15% Neutropenia 11%	RP2D 800 mg
Eyre et al.[79]	n = 20 R/R MCL (median 3 prior lines of therapy) BTKi exposed (90% resistant)	Retrospective analysis of venetoclax at doses of 200-1200 mg daily	ORR 53% CRR 18%	Median PFS 3 months Median OS 9 months	Pneumonia 15%
Zhao et al.[80]	n = 24 R/R MCL (median 5 prior lines of therapy) BTKi resistant: 67%	Retrospective analysis of venetoclax-based regimens: Monotherapy: n = 12  + anti-CD20 antibody: n = 8  + BTKi: n = 3  + chemotherapy: n = 1	ORR 50% CRR 21%	Median PFS 8 months Median OS 13.5 months	NA
Sawalha et al.[81]	n = 81 R/R MCL (median 3 prior lines of therapy)	Retrospective analysis of venetoclax-based regimens: Monotherapy: n = 50  + anti-CD20 antibody: n = 11  + BTKi: n = 16  + other: n = 4	ORR 42% CRR 18%	Median duration of venetoclax treatment 3 months Median OS 13 months	NA
Follicular lymphoma
Davids et al.[35, 38] NCT01328626	n = 29 R/R FL	Phase 1 dose escalation venetoclax monotherapy 200-1200 mg daily	ORR 38% CRR 17%	Median PFS 11 months Median DOR 27 months 12-month OS: 100%	Overall cohort Anemia 15% Neutropenia 11%	RP2D 1200 mg
de Vos et al.[86] NCT01594229	n = 32 R/R FL	Phase 1b dose escalation of venetoclax 50-1200 mg daily plus bendamustine–rutiximabx6	ORR 75% CR 38%	Median PFS and OS not reached	Overall cohort Neutropenia 60% Lymphopenia 38%	RP2D 800 mg in combination with bendamustine–rituximab
CAVALLI Ib [87] NCT02055820	n = 24 R/R FL: n = 4 TN FL: n = 20	Phase 1b dose escalation of venetoclax 200-800 mg in combination with R/G-CHOP	ORR 83% CRR 75%	12-month PFS 100% Ven-R-CHOP and 90% Ven-G-CHOP	Overall cohort Neutropenia 54% Febrile neutropenia 33% Thrombocytopenia 17% Anemia 13%	RP2D 800 mg C1D4-10 and D1-10 for subsequent cycles
Stathis et al.[84] NCT02877550	n = 25 TN FL	Phase I trial of venetoclax 600-800 mg daily plus obinutuzumab for 6 cycles, followed by obinutuzumab maintenance [2 years]	ORR 88% CRR 68%	12-month PFS 77%	Neutropenia 28%	RP2D 800 mg in combination with obinutuzumab
PrECOG 0403 [89] NCT03113422	n = 56 TN FL with high tumor burden	Phase II trial of venetoclax 800 mg plus bendamustine–rituximabx6	CRR 73%	24-month PFS 86% 24-month OS 94%	Neutropenia 16% Thrombocytopenia 14% TLS 14%	Opportunistic infections, combination considered unacceptably immunosuppressive
Zinzani et al.[90] NCT02187861	n = 163 R/R FL Arm A: n = 52 Arm B: n = 51 Arm C: n = 51 Safety run-in: n = 9	Phase II study of: Arm A: Venetoclax 800 mg daily for 1 year plus rituximab C1D1,8,15,22 & D1 of C4, C6, C8, C12 Arm B: Venetoclax 800 mg daily for 1 year plus bendamustine–rutiximabx6 Arm C: Bendamustine–rituximabx6	Arm A: ORR 35% CRR 17% Arm B: ORR 84% CRR 75% Arm C: ORR 84% CRR 69%	18-month PFS Arm A: 27% Arm B: 62% Arm C:59%	Arm A: Neutropenia 25% Arm B: Neutropenia 59% Thrombocytopenia 45% Anemia 14% Febrile neutropenia 12% Arm C: Neutropenia 28%
Diffuse large B cell lymphoma and aggressive B cell lymphomas
Davids et al.[35, 38] NCT01328626	n = 34 R/R DLBCL and PMBCL [2 patients]	Phase 1 dose escalation venetoclax monotherapy 200-1200 mg daily	ORR 18% CRR 12%	Median PFS 1 month 12-month OS: 32%	Overall cohort Anemia 15% Neutropenia 11%	RP2D 1200 mg
de Vos et al.[86] NCT01594229	n = 22 R/R DLBCL	Phase 1b dose escalation of venetoclax 50-1200 mg daily plus bendamustine–rutiximabx6	ORR 41% CR 14%	Median PFS 4 months Median OS 15 months	Overall cohort Neutropenia 60% Lymphopenia 38% Thrombocytopenia 28% Anemia 17%	RP2D 800 mg in combination with bendamustine–rituximab
CAVALLI 1b [87] NCT02055820	n = 18 TN DLBCL	Phase 1b dose escalation of venetoclax 200-800 mg in combination with R/G-CHOP	ORR 89% CRR 89%	12-month PFS 70% Ven-R-CHOP and 100% Ven-G-CHOP	Overall cohort Neutropenia 54% Febrile neutropenia 33% Thrombocytopenia 17% Anemia 13%	RP2D 800 mg C1D4-10 and D1-10 for subsequent cycles
Rutherford et al.[154] NCT03036904	n = 30 TN aggressive B-NHL DHL: n = 15 DLBCL: n = 9 Transformed NHL: n = 2 HGBCL-NOS: n = 2 PMBCL: n = 2	Phase 1 dose escalation of venetoclax 400-800 mg in combination with dose-adjusted-R-EPOCH	ORR 97% CRR 93%	24-month PFS: 83% 24-month OS: 90%	Neutropenia 83% Thrombocytopenia 70% Febrile neutropenia 63% Anemia 60% Serious gastrointestinal AEs 27%	RP2D 600 mg for 5 days per cycle
CAVALLI phase II [93] NCT02055820	n = 206 TN DLBCL IPI 2–5	Phase II study of venetoclax-Rx8 plus CHOPx6-8	ORR 83% CRR 69%	24-month PFS: 80% 24-month OS: 86%	Neutropenia 68% Febrile neutropenia 31% Infections 23% Anemia 24% Thrombocytopenia 22% Leukopenia 10%	Improved PFS compared to historical R-CHOP control (GOYA), esp if BCL2 + by IHC
ALLIANCE A051701 [95] NCT03984448	TN double-hit lymphoma (by FISH or expression) n = 36	Phase II/III randomized study DA-R-EPOCH	ORR 73% CRR 67%	Median PFS and OS not reached (median follow-up 7 months)	Neutropenia 67% Febrile neutropenia 36% Sepsis 14%	Early discontinuation due to excess deaths in DA-R-EPOCH + venetoclax arm
	n = 73	DA-R-EPOCH + venetoclax 600 mg C1D4-8 and C2-6D1-5	ORR 58% CRR 50%	Median PFS 7 months Median OS 9 months	Neutropenia 71% Febrile neutropenia 40% Sepsis 23%
Davids et al. [98] NCT03054896	n = 27 DLBCL-RT	Phase II of C1 DA-R-EPOCH, followed by venetoclax ramp-up, then venetoclax 400 mg D1-10 of C2-6 of DA-R-EPOCH followed by alloSCT/CAR-T or venetoclax 400 mg daily maintenance	ORR 62% CRR 50%	Median PFS 10 months Median OS 20 months	Neutropenia 58% Anemia 62% Thrombocytopenia 50% Febrile neutropenia 38% Hypophosphatemia 23% Hyponatremia 15% Hyperglycemia 15%