Break free from chemotherapy and continuous oral treatment in CLL. VENCLEXTA offers the only chemo-free regimens with a fixed duration of 12 months in 1L CLL with VEN+G and ~24 months in R/R CLL with VEN+R. 1
1L
Designed for patients to complete treatment in 12 months 1
- The CLL14 trial evaluated PFS with VEN+G, a fixed duration treatment regimen
- CLL14 was a multicenter, open-label,
actively controlled, phase 3 trial (randomized 1:1)
Select inclusion criteria
- Coexisting medical conditions (total CIRS >6 or CLcr <70 mL/min), age ≥18 years 1
Select clinical endpoints 1,2
- Primary endpoint: PFS (IRC-assessed PFS was the basis for FDA approval of VEN+G)
- Select secondary endpoints: MRD in bone marrow, CR/CRi (INV-assessed), MRD in peripheral blood, MRD in CR/CRi in bone marrow, MRD in CR/CRi in peripheral blood, ORR (INV-assessed)
*VENCLEXTA oral tablets were administered
according to the 5-week dose ramp-up schedule: 20 mg daily during
Cycle 1, Days 22-28; 50 mg daily during Cycle 2, Days 1-7; 100 mg
daily during Cycle 2, Days 8-14; 200 mg daily during Cycle 2, Days
15-21; 400 mg daily during Cycle 2, Days 22-28 and on Days 1-28 of
all subsequent cycles until the end of Cycle 12.
†GAZYVA intravenous (IV) infusion was administered at
1000 mg on Day 1 (the first dose could be split as 100 mg and 900 mg
on Days 1 and 2), and on Days 8 and 15 of Cycle 1. For all
subsequent 28-day cycles, GAZYVA 1000 mg was administered on Day 1
for a total of 6 cycles.
‡Chlorambucil was
administered at 0.5 mg/kg orally on Days 1 and 15 of each 28-day
cycle for 12 cycles.
ALC=absolute lymphocyte count; CIRS=Cumulative
Illness Rating Scale; CLcr=creatinine
clearance; IRC=Independent Review Committee;
CRi=complete remission with incomplete bone marrow recovery;
INV=investigator; ORR=overall response rate; TLS=tumor lysis
syndrome.
VEN+G was studied in patients whose age and disease characteristics were representative of the broad CLL patient population 2-4
Baseline demographics and disease characteristics 2II
Characteristic | VEN+G (N=216) | GClb (N=216) |
---|---|---|
Age, years; median (range) | 72 (43-89) | 71 (41-89) |
Age ≥70, % | 62 | 59 |
Male, % | 68 | 66 |
Binet stage, % | ||
Binet stage A | 21 | 20 |
Binet stage B | 36 | 37 |
Binet stage C | 43 | 43 |
Median CIRS score (range) | 9 (0-23) | 8 (1-28) |
CLcr <70 mL/min, % | 60 | 55 |
CLL subsets, % | ||
17p deletion | 9 | 7 |
TP53 mutation | 9 | 6 |
11q deletion | 18 | 20 |
lgVH unmutated | 56 | 57 |
lgVH mutated | 35 | 38 |
High TLS risk category, %# | 22 | 20 |
Lymph nodes ≥10 cm | 5 | 5 |
Lymph nodes ≥5 cm and ALC ≥25 x 109/L | 14 | 12 |
Medium TLS risk, % | 64 | 68 |
Low TLS risk, % | 13 | 12 |
ECOG performance status, % | ||
0 | 41 | 48 |
1 | 46 | 41 |
2 | 13 | 12 |
Baseline ALC (x 109/L); median | 56 | 58 |
IIPatients with missing results not
included.
#TLS risk category was chosen based on
investigator discretion, lymph node size, and ALC.
GClb=GAZYVA + chlorambucil; TP53=tumor protein 53; lgVH=immunoglobulin heavy-chain variable gene; ECOG=Eastern Cooperative Oncology Group.
See 1L PFS — Next ›
R/R
Designed to stop treatment at ~24 months 1*
- MURANO was a phase 3, multicenter, open-label, actively controlled trial (randomized 1:1)
- The 5-week VENCLEXTA dose ramp-up was designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS
- Tumor burden assessments, including radiographic evaluation and blood chemistry assessment, are recommended prior to VENCLEXTA initiation to assess the risk for TLS
Select inclusion criteria
- ≥18 years of age; 1-3 prior lines of therapy, including at least 1 chemo-containing regimen; and prior bendamustine only if duration of response (DoR) ≥24 months 5
Select clinical endpoints
- Primary endpoint: PFS (IRC-assessed PFS was the basis for approval of VEN+R) 1
-
Select secondary endpoints: IRC-assessed CR/CRi, IRC-assessed
ORR, OS, INV-assessed PFS, undetectable MRD 5,6
- Key secondary endpoints were ranked for hierarchical
testing as: (1) IRC-assessed CR/CRi rate, (2) IRC-assessed ORR,
and (3) OS. Because the study did not reach significance at the
first key secondary endpoint (IRC-assessed CR/CRi rate), the
remaining key secondary endpoints could not be tested for
statistical significance
- Key secondary endpoints were ranked for hierarchical
testing as: (1) IRC-assessed CR/CRi rate, (2) IRC-assessed ORR,
and (3) OS. Because the study did not reach significance at the
first key secondary endpoint (IRC-assessed CR/CRi rate), the
remaining key secondary endpoints could not be tested for
statistical significance
*From Cycle 1, Day 1 of rituximab, in the absence of disease
progression or unacceptable toxicity.
†VENCLEXTA
oral tablets were administered according to the 5-week dose ramp-up
schedule: 20 mg daily in Week 1, 50 mg daily in Week 2, 100 mg daily
in Week 3, 200 mg daily in Week 4, and 400 mg daily from Week 5
through all subsequent weeks for 24 months from Cycle 1, Day 1 of
rituximab.
‡Rituximab was administered after the
initial VENCLEXTA dose ramp-up and was infused on Day 1 of each
28-day cycle for 6 cycles, with a dose of 375 mg/m2 for
Cycle 1 and 500 mg/m2 for Cycles 2-6.
§Patients randomized
to bendamustine + rituximab received bendamustine at 70
mg/m2 on Days 1 and 2 for 6 cycles (28-day cycle) and
rituximab at the above-described dose and schedule.
R/R=relapsed/refractory; VEN+R=VENCLEXTA +
rituximab; PFS=progression-free survival; TLS=tumor lysis syndrome;
ALC=absolute lymphocyte count; CIRS=Cumulative Illness Rating Scale;
CLcr=creatinine clearance; IRC=Independent Review Committee;
FDA=Food and Drug Administration; MRD=minimal residual disease;
CR=complete remission; CRi=complete remission with incomplete bone
marrow recovery; INV=investigator; ORR=overall response rate;
OS=overall survival.
Baseline patient characteristics were generally well balanced between study arms 6,7
MURANO demographics and baseline characteristicsII
Characteristic | VEN+R (N=194) | BR (N=195) |
---|---|---|
Age, years; median (range) | 65 (28-83) | 66 (22-85) |
Male, % | 70 | 77 |
ECOG performance status, % | ||
0 | 57 | 56 |
1 | 42 | 43 |
2 | 1 | 1 |
Tumor burden, % | ||
Absolute lymphocyte count ≥25 x 109/L | 67 | 69 |
1 or more nodes ≥5 cm | 46 | 48 |
Fludarabine refractory, % | 14 | 16 |
CLL subsets, % | ||
17p deletion | 27 | 27 |
11q deletion | 35 | 38 |
TP53 mutation | 25 | 28 |
lgVH unmutated | 68 | 68 |
Time since diagnosis, years; median (range) | 6.44 (0.5-28.4) | 7.11 (0.3-29.5) |
IIPatients with missing results not included.
GClb=GAZYVA + chlorambucil; TP53=tumor
protein 53; lgVH=immunoglobulin heavy-chain variable gene;
ECOG=Eastern Cooperative Oncology Group.
The majority of patients in the study had 1 prior therapy.
Chemotherapy with or without anti-CD20 was the most common prior
therapy 1,6-8
MURANO prior therapies
Number of prior lines of therapy, % | VEN+R (N=194) | BR (N=195) |
---|---|---|
Median number (range) | 1 (1-5) | |
1 | 57 | 60 |
2 | 30 | 22 |
≥3 | 13 | 18 |
Previous CLL regimens | ||
Median number (range) | 1 (1-5) | |
Prior alkylating agents, % | 95 | 93 |
Prior purine analogs, % | 81 | 81 |
Prior anti-CD20 antibodies, % | 76 | 79 |
Prior B-cell receptor pathway inhibitors, % | 2 | 3 |
Prior FCR, % | 54 | 55 |
Prior BR, % | 2 | 3 |
BR=bendamustine + rituximab; FCR=fludarabine, cyclophosphamide, rituximab.