Table 1.

Venetoclax in chronic lymphocytic leukemia: clinical trial data summary.

Study	Treatment arms	Design	Patient characteristics	Response rates	Survival measures	Main AEs (>10%)
[Roberts et al. 2016]	Monotherapy phase I/II phase I (n = 56). After protocol change, trial continued as phase II. Total n = 116	Phase I. Single dose of VEN on week 1, day –3 or –7 followed by continuous once-daily dosing from week 1, day1, until disease progression or unacceptable toxicity	R/R Del(17p) – 31/102 (30%) F-refractory - 70 (60%)	ORR 79% CR/CRi 20% (expansion cohort data have not matured)	Med f/u 14.7 months Med PFS 25 months (56 pts in dose-escalating cohort)	G3/4 AEs: neutropenia (41%), anemia (12%), thrombocytopenia (12%). TLS: 10 pts (18%), clinical in 3, including 1 death
		Trial continued as phase II, with weekly dose increases from 20, 50, 100, 200 mg to the final recommended dose of 400 mg daily
[Ma et al. 2015]	VEN-R phase Ib n = 49	VEN: ramp-up dose schedule, to a final dose of 200–600 mg/day R: every 4 weeks for a total of 6 doses; 400 mg selected to move forward	Age 68y (50–88) 2 (1–5) prior Tx R-ref 29% F-ref 18% Del(17p) 20% Unm. IGHV 70%	ORR 86% CR/CRi 41% BM MRD neg 53% (75% in pts with CR)	Med f/u 17.5 months PFS 87% at 12 months PFS 84% at 24 months OS 94% at 12 months 5/6 pts with PD had RT	1 fatal TLS prior to protocol modification G3/4 AEs: neutropenia (53%), thrombocytopenia (16%), anemia (14%), febrile neutropenia (12%)
[Salles et al. 2015]	VEN-BR phase I	After dose-finding phase, daily VEN dose at 400 mg Schedule A: VEN→BR Schedule B: BR→VEN Benda 70 mg/m2 in R/R; 90 mg/m2 in 1L R 375 mg/m2 C1; 500 mg/m2 C2–6. Finally, schedule B selected.	R/R (n = 20) 1L (n = 10) Age 63y (22–77)			No TLS events (lab and clinical) Schedule A is as safe as B in R/R pts. G3/4 AEs: neutropenia (57%), thrombocytopenia (17%)
[Flinn et al. 2015]	VEN-G phase I	3 + 3 design, VEN ramp-up dose schedule and TLS prophylaxis, to a final dose of 100–400 mg/d (600 mg was finally not explored). Schedule A: VEN→G Schedule B: G→VEN 6 cycles R/R– VEN till PD 1L VEN for another 6 months	Age 62.5y (45–80), R/R (n = 26), 1L (n = 6)	Only in R/R pts (n = 17), ORR 100% CR/CRi 23%		G3/4 AEs: Lab TLS (12.5%), neutropenia (47%), infections (19%). 1 death (acute respiratory failure)
[Fischer et al. 2015]	VEN-G versus chl-G CLL14 trial phase III safety run-in period	6 cycles of VEN-G + 6 additional cycles of VEN G administered according to CLL11. A ramp-up schedule of VEN up to 400 mg/d starting d22 of cycle 1	1L unfit pts (n = 13) CIRS > 6 or CrCl <70 ml/min Age 75y (59–88)			G3/4 AEs: neutropenia (23%), all other: 15% (2 pts): infusion-related reaction, lab TLS, thrombocytopenia, infections
[Jones et al. 2015a]	VEN monotherapy after ibrutinib or idelalisib failure	Ramp-up schedule to 400 mg/d	R/R after: ibrutinib (n = 41), median time 19w (0.5–39) or idelalisib (n = 13), median time 10w (0.5–29)	Of evaluable pts: Ibrutinib, ORR 61% (3 CRs); idelalisib, ORR 50% (all PR)		10 pts discontinued VEN, 5 d/t PD
[Stilgenbaueret al. 2015]	VEN monotherapy in del(17p) CLL pts n = 107	Dose ramp-up escalation and TLS prophylaxis. VEN at 400 mg/d	R/R Age 67y (37–85); 34/78 F-refractory; 38/54 B-refractory	Med f/u 12.1 months ORR 79% CR/CRi 7.5% 18/45 (17%) MRD-neg.	PFS at 12 months 72% OS at 12 months 87% 22 pts progressed, 9 with RT	G3/a AEs: neutropenia 40%, anemia 18%, thrombocytopenia 15%, infections 20%

1L, first line; AEs, adverse events; BM, bone marrow; BR, bendamustine-rituximab; C, cycle; CIRS, Cumulative Illness Rating Scale; CLL, chronic lymphocytic leukemia; CR, complete remission; CRi, CR with incomplete bone marrow recovery; f/u, follow up; IGHV, immunoglobulin heavy chain variable; Med, median; MRD, minimal residual disease; neg., negative; ORR, overall response rate; OS, overall survival; PD, progressive disease; pts, patients; PFS, progression-free survival; PR, partial response; R, rituximab; R/R, relapsed and refractory; RT, Richter’s transformation; TLS, tumor lysis syndrome; Tx, treatment; Unm.; unmutated; VEN, venetoclax.