|
|
Week 1 | 20 mg |
Week 2 | 50 mg |
Week 3 | 100 mg |
Week 4 | 200 mg |
Week 5 and beyond | 400 mg |
Oral Daily Dose |
||
Day 1 | 100 mg | |
Day 2 | 200 mg | |
Day 3 | 400 mg | |
Days 4 and beyond | 400 mg orally once daily of each 28-day cycle in combination with |
600 mg orally once daily of each 28-day cycle in combination with |
|
|
|
||
|
hyperuricemics |
|
||
Low | All LN <5 cm AND ALC <25 x109/L |
Oral (1.5 to 2 L) |
Allopurinol | Outpatient
|
Medium | Any LN 5 to <10 cm OR ALC ≥25 x109/L |
Oral (1.5 to 2 L) and consider additional intravenous |
Allopurinol | Outpatient
|
High | Any LN ≥10 cm OR ALC ≥25 x109/L AND any LN ≥5 cm |
Oral (1.5 to 2 L) and intravenous (150 to 200 mL/hr as tolerated) |
Allopurinol; consider rasburicase if baseline uric acid is elevated | In hospital
|
ALC = absolute lymphocyte count; CLcr = creatinine clearance; LN = lymph node. aAdminister intravenous hydration for any patient who cannot tolerate oral hydration. bStart allopurinol or xanthine oxidase inhibitor 2 to 3 days prior to initiation of VENCLEXTA. cEvaluate blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine); review in real time. dFor patients at risk of TLS, monitor blood chemistries at 6 to 8 hours and at 24 hours at each subsequent ramp-up dose. |
|
|
|
|
||
Blood chemistry changes or symptoms suggestive of TLS |
Any | Withhold the next day’s dose. If resolved within 24 to 48 hours of last dose, resume at same dose. |
For any blood chemistry changes requiring more than 48 hours to resolve, resume at reduced dose (see |
||
For any events of clinical TLS,b resume at reduced dose following resolution (see |
||
|
||
Grade 3 or 4 non-hematologic toxicities |
1st occurrence | Interrupt VENCLEXTA. Upon resolution to Grade 1 or baseline level, resume VENCLEXTA at the same dose. |
2nd and subsequent occurrences | Interrupt VENCLEXTA. Follow dose reduction guidelines in |
|
|
||
Grade 3 neutropenia with infection or fever; or Grade 4 hematologic toxicities (except lymphopenia) |
1st occurrence | Interrupt VENCLEXTA. Upon resolution to Grade 1 or baseline level, resume VENCLEXTA at the same dose. |
2nd and subsequent occurrences | Interrupt VENCLEXTA. Follow dose reduction guidelines in |
|
Consider discontinuing VENCLEXTA for patients who require dose reductions to less than 100 mg for more than 2 weeks. aAdverse reactions were graded using NCI CTCAE version 4.0. bClinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or sudden death and/or seizures |
|
|
400 | 300 |
300 | 200 |
200 | 100 |
100 | 50 |
50 | 20 |
20 | 10 |
aDuring the ramp-up phase, continue the reduced dose for 1 week before increasing the dose. bIf a dosage interruption lasts more than 1 week during the ramp-up phase or more than 2 weeks after completion of ramp-up, reassess the risk of TLS and determine if reinitiation at a reduced dosage is necessary |
|
|
|
|
||
Grade 4 neutropenia with or without fever or infection; or Grade 4 thrombocytopenia |
Occurrence prior to achieving remissiona | In most instances, do not interrupt VENCLEXTA in combination with azacitidine, decitabine, or low-dose cytarabine due to cytopenias prior to achieving remission. |
First occurrence after achieving remission and lasting at least 7 days | Delay subsequent cycle of VENCLEXTA in combination with azacitidine, decitabine, or low-dose cytarabine and monitor blood counts. Upon resolution to Grade 1 or 2, resume VENCLEXTA at the same dose in combination with azacitidine, decitabine, or low-dose cytarabine. |
|
Subsequent occurrences in cycles after achieving remission and lasting 7 days or longer | Delay subsequent cycle of VENCLEXTA in combination with azacitidine, or decitabine, or low-dose cytarabine and monitor blood counts. Upon resolution to Grade 1 or 2, resume VENCLEXTA at the same dose in combination with azacitidine, decitabine, or low-dose cytarabine, and reduce VENCLEXTA duration by 7 days during each of the subsequent cycles, such as 21 days instead of 28 days. |
|
|
||
Grade 3 or 4 non-hematologic toxicities |
Any occurrence | Interrupt VENCLEXTA if not resolved with supportive care. Upon resolution to Grade 1 or baseline level, resume VENCLEXTA at the same dose. |
aRecommend bone marrow evaluation. |
Drug |
Ramp-Up Phase |
(After Ramp-Up Phase) |
|
Posaconazole | CLL/SLL | Contraindicated | Reduce VENCLEXTA dose to 70 mg. |
AML | Day 1 – 10 mg Day 2 – 20 mg Day 3 – 50 mg Day 4 – 70 mg |
||
Other strong CYP3A inhibitor |
CLL/SLL | Contraindicated | Reduce VENCLEXTA dose to 100 mg. |
AML | Day 1 – 10 mg Day 2 – 20 mg Day 3 – 50 mg Day 4 – 100 mg |
||
Moderate CYP3A inhibitor |
Reduce the VENCLEXTA dose by at least 50%. | ||
P-gp inhibitor | |||
aIn patients with CLL/SLL, consider alternative medications or reduce the VENCLEXTA dose as described in |
|
|
10 mg | Round, biconvex shaped, pale yellow film-coated tablet debossed with “V” on one side and “10” on the other side |
50 mg | Oblong, biconvex shaped, beige film-coated tablet debossed with “V” on one side and “50” on the other side |
100 mg | Oblong, biconvex shaped, pale yellow film-coated tablet debossed with “V” on one side and “100” on the other side |
|
(N = 212) |
(N = 214) |
||
(%) |
(%) |
(%) |
(%) |
|
|
||||
Neutropeniaa | 60 | 56 | 62 | 52 |
Anemiaa | 17 | 8 | 20 | 7 |
|
||||
Diarrhea | 28 | 4 | 15 | 1 |
Nausea | 19 | 0 | 22 | 1 |
Constipation | 13 | 0 | 9 | 0 |
Vomiting | 10 | 1 | 8 | 1 |
|
||||
Fatiguea | 21 | 2 | 23 | 1 |
|
||||
Upper respiratory tract infectiona |
17 | 1 | 17 | 1 |
aIncludes multiple adverse reaction terms. |
|
Obinutuzumab (N = 212) |
Chlorambucil (N = 214) |
||
(%) |
(%) |
(%) |
(%) |
|
|
||||
Leukopenia | 90 | 46 | 89 | 41 |
Lymphopenia | 87 | 57 | 87 | 51 |
Neutropenia | 83 | 63 | 79 | 56 |
Thrombocytopenia | 68 | 28 | 71 | 26 |
Anemia | 53 | 15 | 46 | 11 |
|
||||
Blood creatinine increased | 80 | 6 | 74 | 2 |
Hypocalcemia | 67 | 9 | 58 | 4 |
Hyperkalemia | 41 | 4 | 35 | 3 |
Hyperuricemia | 38 | 38 | 38 | 38 |
aIncludes laboratory abnormalities that were new or worsening, or with worsening from baseline unknown. |
|
(N = 194) |
(N = 188) |
||
(%) |
(%) |
(%) |
(%) |
|
|
||||
Neutropeniaa | 65 | 62 | 50 | 44 |
Anemiaa | 16 | 11 | 23 | 14 |
|
||||
Diarrhea | 40 | 3 | 17 | 1 |
Nausea | 21 | 1 | 34 | 1 |
Constipation | 14 | <1 | 21 | 0 |
|
||||
Upper respiratory tract infectiona |
39 | 2 | 23 | 2 |
Lower respiratory tract infectiona |
18 | 2 | 10 | 2 |
Pneumoniaa | 10 | 7 | 14 | 10 |
|
||||
Fatiguea | 22 | 2 | 26 | <1 |
aIncludes multiple adverse reaction terms. |
|
(N = 194) |
(N = 188) |
||
(%) |
(%) |
(%) |
(%) |
|
|
||||
Leukopenia | 89 | 46 | 81 | 35 |
Lymphopenia | 87 | 56 | 79 | 55 |
Neutropenia | 86 | 64 | 84 | 59 |
Anemia | 50 | 12 | 63 | 15 |
Thrombocytopenia | 49 | 15 | 60 | 20 |
|
||||
Blood creatinine increased | 77 | <1 | 78 | 1 |
Hypocalcemia | 62 | 5 | 51 | 2 |
Hyperuricemia | 36 | 36 | 33 | 33 |
Hyperkalemia | 24 | 3 | 19 | 2 |
aIncludes laboratory abnormalities that were new or worsening, or with worsening from baseline unknown. |
|
(N = 352) |
|
(%) |
(%) |
|
|
||
Neutropeniaa | 50 | 45 |
Anemiaa | 33 | 18 |
Thrombocytopeniaa | 29 | 20 |
Lymphopeniaa | 11 | 7 |
Febrile neutropenia | 6 | 6 |
|
||
Diarrhea | 43 | 3 |
Nausea | 42 | 1 |
Abdominal paina | 18 | 3 |
Vomiting | 16 | 1 |
Constipation | 16 | <1 |
Mucositisa | 13 | <1 |
|
||
Upper respiratory tract infectiona | 36 | 1 |
Pneumoniaa | 14 | 8 |
Lower respiratory tract infectiona | 11 | 2 |
|
||
Fatiguea | 32 | 4 |
Edemaa | 22 | 2 |
Pyrexia | 18 | <1 |
|
||
Musculoskeletal paina | 29 | 2 |
Arthralgia | 12 | <1 |
|
||
Cougha | 22 | 0 |
Dyspneaa | 13 | 1 |
|
||
Headache | 18 | <1 |
Dizzinessa | 14 | 0 |
|
||
Rasha | 18 | <1 |
Adverse reactions graded using NCI Common Terminology Criteria for Adverse Events version 4.0. aIncludes multiple adverse reaction terms. |
|
(N = 352) |
|
(%) |
(%) |
|
|
||
Leukopenia | 89 | 42 |
Neutropenia | 87 | 63 |
Lymphopenia | 74 | 40 |
Anemia | 71 | 26 |
Thrombocytopenia | 64 | 31 |
|
||
Hypocalcemia | 87 | 12 |
Hyperglycemia | 67 | 7 |
Hyperkalemia | 59 | 5 |
AST increased | 53 | 3 |
Hypoalbuminemia | 49 | 2 |
Hypophosphatemia | 45 | 11 |
Hyponatremia | 40 | 9 |
aIncludes laboratory abnormalities that were new or worsening, or worsening from baseline unknown. |
|
(N = 283) |
(N = 144) |
||
(%) |
(%) |
(%) |
(%) |
|
|
||||
Nausea | 44 | 2 | 35 | <1 |
Diarrheaa | 43 | 5 | 33 | 3 |
Vomitingb | 30 | 2 | 23 | <1 |
Stomatitisc | 18 | 1 | 13 | 0 |
Abdominal paind | 18 | <1 | 13 | 0 |
|
||||
Febrile neutropenia | 42 | 42 | 19 | 19 |
|
||||
Musculoskeletal paine | 36 | 2 | 28 | 1 |
|
||||
Fatiguef | 31 | 6 | 23 | 2 |
Edemag | 27 | <1 | 19 | 0 |
|
||||
Hemorrhageh | 27 | 7 | 24 | 3 |
Hypotensioni | 12 | 5 | 8 | 3 |
|
||||
Decreased appetitej | 25 | 4 | 17 | <1 |
|
||||
Rashk | 25 | 1 | 15 | 0 |
|
||||
Sepsisl (excluding fungal) | 22 | 22 | 16 | 14 |
Urinary tract infectionm | 16 | 6 | 9 | 6 |
|
||||
Dyspnean | 18 | 4 | 10 | 2 |
|
||||
Dizzinesso | 17 | <1 | 8 | <1 |
aIncludes diarrhea and colitis. bIncludes vomiting and hematemesis. cIncludes stomatitis, mouth ulceration, mucosal inflammation, cheilitis, aphthous ulcer, glossitis, and tongue ulceration. dIncludes abdominal pain, abdominal pain upper, abdominal discomfort, and abdominal pain lower. eIncludes arthralgia, back pain, pain in extremity, musculoskeletal pain, bone pain, myalgia, neck pain, non-cardiac chest pain, arthritis, musculoskeletal chest pain, musculoskeletal stiffness, spinal pain, and musculoskeletal discomfort. fIncludes fatigue and asthenia. gIncludes edema peripheral, edema, generalized edema, eyelid edema, face edema, penile edema, periorbital edema, and swelling. hIncludes epistaxis, hematuria, conjunctival hemorrhage, hemoptysis, hemorrhoidal hemorrhage, gingival bleeding, mouth hemorrhage, hemorrhage intracranial, vaginal hemorrhage, cerebral hemorrhage, gastrointestinal hemorrhage, muscle hemorrhage, skin hemorrhage, upper gastrointestinal hemorrhage, anal hemorrhage, eye hemorrhage, gastritis hemorrhagic, hemorrhage, hemorrhage urinary tract, hemorrhagic diathesis, hemorrhagic stroke, hemorrhagic vasculitis, lower gastrointestinal hemorrhage, mucosal hemorrhage, penile hemorrhage, post procedural hemorrhage, rectal hemorrhage, retinal hemorrhage, shock hemorrhagic, soft tissue hemorrhage, subdural hemorrhage, tongue hemorrhage, urethral hemorrhage, vessel puncture site hemorrhage, vitreous hemorrhage, and wound hemorrhage. iIncludes hypotension and orthostatic hypotension. jIncludes decreased appetite and hypophagia. kIncludes rash, rash maculo-papular, rash macular, drug eruption, rash papular, rash pustular, eczema, rash erythematous, rash pruritic, dermatitis acneiform, rash morbilliform, dermatitis, eczema asteatotic, exfoliative rash, and perivascular dermatitis. lIncludes sepsis, escherichia bacteremia, escherichia sepsis, septic shock, bacteremia, staphylococcal bacteremia, klebsiella bacteremia, staphylococcal sepsis, streptococcal bacteremia, enterococcal bacteremia, klebsiella sepsis, pseudomonal bacteremia, pseudomonal sepsis, urosepsis, bacterial sepsis, clostridial sepsis, enterococcal sepsis, neutropenic sepsis, and streptococcal sepsis. mIncludes urinary tract infection, escherichia urinary tract infection, cystitis, urinary tract infection enterococcal, urinary tract infection bacterial, pyelonephritis acute, and urinary tract infection pseudomonal. nIncludes dyspnea, dyspnea exertional, and dyspnea at rest. oIncludes dizziness and vertigo. |
|
Azacitidine |
Azacitidine |
||
(%) |
(%) |
(%) |
(%) |
|
|
||||
Neutrophils decreased | 98 | 98 | 88 | 81 |
Platelet decreased | 94 | 88 | 94 | 80 |
Lymphocytes decreased | 91 | 71 | 72 | 39 |
Hemoglobin decreased | 61 | 57 | 56 | 52 |
|
||||
Bilirubin increased | 53 | 7 | 40 | 4 |
Calcium decreased | 51 | 6 | 39 | 9 |
Sodium decreased | 46 | 14 | 47 | 8 |
Alkaline phosphatase increased | 42 | 1 | 29 | <1 |
Blood bicarbonate decreased | 31 | <1 | 25 | 0 |
The denominator used to calculate the rate varied from 85 to 144 in the PBO+AZA arm and from 125 to 283 in the VEN+AZA arm based on the number of patients with at least one post-treatment value. |
|
Cytarabine (N = 142) |
Cytarabine (N = 68) |
||
(%) |
(%) |
(%) |
(%) |
|
|
||||
Nausea | 42 | 1 | 31 | 0 |
Diarrhea | 28 | 3 | 16 | 0 |
Vomiting | 25 | <1 | 13 | 0 |
Abdominal paina | 15 | <1 | 9 | 3 |
Stomatitisb | 15 | 1 | 6 | 0 |
|
||||
Febrile neutropenia | 32 | 32 | 29 | 29 |
|
||||
Pneumoniac | 29 | 19 | 21 | 21 |
|
||||
Hemorrhaged | 27 | 8 | 16 | 1 |
Hypotensione | 11 | 5 | 4 | 1 |
|
||||
Musculoskeletal painf | 23 | 3 | 18 | 0 |
|
||||
Fatigueg | 22 | 2 | 21 | 0 |
|
||||
Headache | 11 | 0 | 6 | 0 |
aIncludes abdominal pain, abdominal pain upper, abdominal discomfort, and abdominal pain lower. bIncludes stomatitis, mouth ulceration, aphthous ulcer, glossitis, mucosal inflammation, and tongue ulceration. cIncludes pneumonia, lung infection, lower respiratory tract infection, pneumonia fungal, lower respiratory tract infection fungal, pneumocystis jirovecii pneumonia, pneumonia aspiration, pneumonia cytomegaloviral, and pneumonia pseudomonal. dIncludes epistaxis, conjunctival hemorrhage, hemoptysis, gastrointestinal hemorrhage, gingival bleeding, mouth hemorrhage, upper gastrointestinal hemorrhage, hematuria, retinal hemorrhage, catheter site hemorrhage, cerebral hemorrhage, gastric hemorrhage, gastritis hemorrhagic, hemorrhage intracranial, hemorrhage subcutaneous, lip hemorrhage, mucosal hemorrhage, pharyngeal hemorrhage, post procedural hemorrhage, pulmonary alveolar hemorrhage, pulmonary hemorrhage, tooth pulp hemorrhage, uterine hemorrhage, and vascular access site hemorrhage. eIncludes hypotension and orthostatic hypotension. fIncludes back pain, arthralgia, pain in extremity, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, arthritis, bone pain, musculoskeletal chest pain, and spinal pain. gIncludes fatigue and asthenia. |
|
Cytarabine |
Cytarabine |
||
(%) |
(%) |
(%) |
(%) |
|
|
||||
Platelets decreased | 97 | 95 | 92 | 90 |
Neutrophils decreased | 95 | 92 | 82 | 71 |
Lymphocytes decreased | 92 | 69 | 65 | 24 |
Hemoglobin decreased | 63 | 57 | 57 | 54 |
|
||||
Bilirubin increased | 61 | 7 | 38 | 7 |
Albumin decreased | 61 | 6 | 43 | 4 |
Potassium decreased | 56 | 16 | 42 | 14 |
Calcium decreased | 53 | 8 | 45 | 13 |
Glucose increased | 52 | 13 | 59 | 9 |
AST increased | 36 | 6 | 37 | 1 |
Alkaline phosphatase increased | 34 | 1 | 26 | 1 |
ALT increased | 30 | 4 | 26 | 1 |
Sodium increased | 11 | 3 | 6 | 1 |
The denominator used to calculate the rate varied from 38 to 68 in the PBO+LDAC arm and from 65 to 142 in the VEN+LDAC arm based on the number of patients with at least one post-treatment value. |
|
Obinutuzumab (N = 216) |
Chlorambucil (N = 216) |
|
||
Number of events, n (%) | 29 (13) | 79 (37) |
Disease progression | 14 (6) | 71 (33) |
Death | 15 (7) | 8 (4) |
Median, months | Not Reached | Not Reached |
HR (95% CI)b | 0.33 (0.22, 0.51) | |
p-valueb | <0.0001 | |
|
||
ORRd | 183 (85) | 154 (71) |
95% CI | (79, 89) | (65, 77) |
CR | 100 (46) | 47 (22) |
CR+CRid | 107 (50) | 50 (23) |
PR | 76 (35) | 104 (48) |
CI = confidence interval; CR = complete remission; CRi = complete remission with incomplete marrow recovery; HR = hazard ratio; ORR = overall response rate (CR + CRi + PR); PR = partial remission. aFrom randomization until earliest event of disease progression or death due to any cause. IRC-assessed; Kaplan-Meier estimate. bHR estimate is based on Cox-proportional hazards model stratified by Binet Stage and geographic region; p-value based on log rank test stratified by the same factors. cPer 2008 International Workshop for Chronic Lymphocytic Leukemia (IWCLL) guidelines. dp-values based on Cochran-Mantel-Haenszel test; p=0.0007 for ORR; p<0.0001 for CR+CRi. |
Obinutuzumab |
Chlorambucil |
|
|
||
N | 216 | 216 |
Bone marrow, n (%) | 123 (57) | 37 (17) |
95% CI | (50, 64) | (12, 23) |
p-valuea | <0.0001 | |
Peripheral blood, n (%) | 163 (76) | 76 (35) |
95% CI | (69, 81) | (29, 42) |
p-valuea | <0.0001 | |
|
||
N | 100 | 47 |
Bone marrow, n (%) | 69 (69) | 21 (45) |
95% CI | (59, 78) | (30, 60) |
p-valuea | 0.0048 | |
Peripheral blood, n (%) | 87 (87) | 29 (62) |
95% CI | (79, 93) | (46, 75) |
p-valuea | 0.0005 | |
CI = confidence interval; CR = complete remission. ap-value based on Chi-square test. |
|
(N = 194) |
(N = 195) |
|
||
Number of events, n (%) | 35 (18) | 106 (54) |
Disease progression, n | 26 | 91 |
Death events, n | 9 | 15 |
Median, months (95% CI) | Not Reached | 18.1 (15.8, 22.3) |
HR (95% CI)b | 0.19 (0.13, 0.28) | |
p-valueb | <0.0001 | |
|
||
ORR | 179 (92) | 141 (72) |
95% CI | (88, 96) | (65, 78) |
CR+CRi | 16 (8) | 7 (4) |
nPR | 3 (2) | 1 (1) |
PR | 160 (82) | 133 (68) |
CI = confidence interval; CR = complete remission; CRi = complete remission with incomplete marrow recovery; HR = hazard ratio; nPR = nodular partial remission; ORR = overall response rate (CR + CRi + nPR + PR); PR = partial remission. aKaplan-Meier estimate. bHR estimate is based on Cox-proportional hazards model stratified by 17p deletion, risk status, and geographic region; p-value based on log-rank test stratified by the same factors. cPer 2008 International Workshop for Chronic Lymphocytic Leukemia (IWCLL) guidelines. |
|
|
Age, years; median (range) | 67 (37-83) |
White; % | 97 |
Male; % | 65 |
ECOG performance status; % 0 1 2 |
40 52 8 |
Tumor burden; % Absolute lymphocyte count ≥25 x 109/L One or more nodes ≥5 cm |
50 53 |
Number of prior therapies; median (range) | 2.5 (1-10) |
Time since diagnosis, years; median (range)a | 6.6 (0.1-32.1) |
ECOG = Eastern Cooperative Oncology Group. aN=105. |
|
N |
ORR, n (%)a
(95% CI) |
85 (80) (71, 87) |
CR + CRi, n (%) CR, n (%) CRi, n (%) |
8 (8) 6 (6) 2 (2) |
nPR, n (%) | 3 (3) |
PR, n (%) | 74 (70) |
CI = confidence interval; CR = complete remission; CRi = complete remission with incomplete marrow recovery; IRC = independent review committee; nPR = nodular partial remission; ORR = overall response rate (CR + CRi + nPR + PR); PR = partial remission. aPer 2008 IWCLL guidelines. |
|
N = 286 |
N = 145 |
Age, years; median (range) | 76 (49, 91) | 76 (60, 90) |
Race | ||
White; % | 76 | 75 |
Black or African American; % | 1 | 1.4 |
Asian; % | 23 | 23 |
Males; % | 60 | 60 |
ECOG performance status; % | ||
0-1 | 55 | 56 |
2 | 40 | 41 |
3 | 5.6 | 3.4 |
Bone marrow blast; % | ||
<30% | 30 | 28 |
≥30% to <50% | 21 | 23 |
≥50% | 49 | 49 |
Disease history; % | ||
De Novo AML | 75 | 76 |
Secondary AML | 25 | 24 |
Cytogenetic risk detecteda, % | ||
Intermediate | 64 | 61 |
Poor | 36 | 39 |
Mutation analyses detected; n/Nb (%) | ||
|
61/245 (25) | 28/127 (22) |
|
23/245 (9.4) | 11/127 (8.7) |
|
40/245 (16) | 18/127 (14) |
|
29/206 (14) | 22/108 (20) |
|
27/163 (17) | 17/86 (20) |
|
38/163 (23) | 14/86 (16) |
aPer the 2016 National Comprehensive Cancer Network (NCCN) Guidelines. bNumber of evaluable BMA specimens received at baseline. |
|
(N |
(N |
|
||
Mediana, months (95% CI) |
14.7 (11.9, 18.7) |
9.6 (7.4, 12.7) |
Hazard ratiob (95% CI) | 0.66 (0.52, 0.85) | |
p-valueb | <0.001 | |
|
||
CR, n (%) | 105 (37) | 26 (18) |
(95% CI) | (31, 43) | (12, 25) |
p-valuec | <0.001 | |
Median DOCRa,d (months) | 18.0 | 13.4 |
95% CI | (15.3, -) | (8.7, 17.6) |
CR+CRh, n (%) | 185 (65) | 33 (23) |
(95% CI) | (59, 70) | (16, 30) |
p-valuec | <0.001 | |
Median DOCR+CRha,e (months) | 17.8 | 13.9 |
95% CI | (15.3, -) | (10.4, 15.7) |
CI = confidence interval; CR = complete remission; CRh = complete remission with partial hematologic recovery; DOCR = duration of CR; HR = hazard ratio; - = not reached. CR (complete remission) was defined as absolute neutrophil count >1,000/microliter, platelets >100,000/microliter, red blood cell transfusion independence, and bone marrow with <5% blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh (complete remission with partial hematological recovery) was defined as <5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter). aKaplan-Meier estimate. bHazard ratio estimate (VEN+AZA vs. PBO+AZA) is based on Cox-proportional hazards model stratified by cytogenetics (intermediate risk, poor risk) and age (18 to <75, ≥75 years) as assigned at randomization; p-value based on log-rank test stratified by the same factors. cp-value is from Cochran-Mantel-Haenszel test stratified by age and cytogenetics risk. dDuration of CR is defined as the number of days from the date of first response of CR to the date of earliest evidence of confirmed morphologic relapse, confirmed progressive disease or death due to disease progression. eDuration of CR+CRh is defined as the number of days from the date of first response of CR+CRh (the first of either CR or CRh) to the date of earliest evidence of confirmed morphologic relapse, confirmed progressive disease, or death due to disease progression. |
|
+ Azacitidine N = 67 |
+ Decitabine N = 13 |
Age, years; median (range) | 76 (61-90) | 75 (68-86) |
Race; % | ||
White | 87 | 77 |
Black or African American | 4.5 | 0 |
Asian | 1.5 | 0 |
Native Hawaiian or Pacific Islander | 1.5 | 15 |
American Indian/Alaskan Native | 0 | 7.7 |
Unreported other | 6 | 0 |
Male; % | 60 | 38 |
ECOG performance status; % 0-1 2 3 |
64 33 3 |
92 7.7 0 |
Disease history; % De Novo AML Secondary AML |
73 27 |
85 15 |
Mutation analyses detecteda; % | ||
|
15 | 31 |
|
27 | 0 |
|
16 | 23 |
|
19 | 15 |
Cytogenetic risk detectedb,c; % | ||
Intermediate | 64 | 38 |
Poor | 34 | 62 |
Baseline comorbiditiesd; % | ||
Severe cardiac disease | 4.5 | 7.7 |
Severe pulmonary disease | 1.5 | 0 |
Moderate hepatic impairment | 9 | 0 |
Creatinine clearance <45 mL/min | 13 | 7.7 |
ECOG = Eastern Cooperative Oncology Group. aIncludes 6 patients with insufficient sample for analysis in the azacitidine group and 4 in the decitabine group. bAs defined by the National Comprehensive Cancer Network (NCCN) risk categorization v2014. cNo mitosis in 1 patient in azacitidine group (excluded favorable risk by Fluorescence in situ Hybridization [FISH] analysis). dPatients may have had more than one comorbidity. |
|
Azacitidine N = 67 |
Decitabine N = 13 |
CR, n (%) | 29 (43) | 7 (54) |
(95% CI) | (31, 56) | (25, 81) |
CRh, n (%) | 12 (18) | 1 (7.7) |
(95% CI) | (9.6, 29) | (0.2, 36) |
CI = confidence interval; CR = complete remission; CRh = complete remission with partial hematological recovery. |
|
+ Low-Dose Cytarabine N = 143 |
+ Low-Dose Cytarabine N = 68 |
Age, years; median (range) | 76 (36, 93) | 76 (41, 88) |
Race; % | ||
White | 71 | 69 |
Black or African American | 1.4 | 1.5 |
Asian | 27 | 29 |
Male; % | 55 | 57 |
ECOG performance status; % 0-1 2 3 |
52 44 4.2 |
50 37 13 |
Disease history; % De Novo AML Secondary AML |
59 41 |
66 34 |
Mutation analyses detected; n/Na (%) | ||
|
22/112 (20) | 9/52 (17) |
|
21/112 (19) | 12/52 (23) |
|
20/112 (18) | 9/52 (17) |
|
18/112 (16) | 7/52 (13) |
Cytogenetic risk detectedb; % | ||
Favorable | <1 | 4 |
Intermediate | 63 | 63 |
Poor | 33 | 29 |
aNumber of evaluable BMA specimens received at baseline. bPer the 2016 National Comprehensive Cancer Network (NCCN) Guidelines. |
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with Low-Dose Cytarabine N = 61 |
Age, years; median (range) | 76 (63-90) |
Race; % | |
White | 92 |
Black or African American | 1.6 |
Asian | 1.6 |
Unreported | 4.9 |
Male; % | 74 |
ECOG performance status; % 0-1 2 3 |
66 33 1.6 |
Disease history; % De Novo AML Secondary AML |
54 46 |
Mutation analyses detecteda; % | |
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8.2 |
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23 |
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21 |
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9.8 |
Cytogenetic risk detectedb; % | |
Intermediate | 59 |
Poor | 34 |
No mitoses | 6.6 |
Baseline comorbiditiesc; % | |
Severe cardiac disease | 9.8 |
Moderate hepatic impairment | 4.9 |
Creatinine clearance ≥30 or <45 mL/min | 3.3 |
aIncludes 7 patients with insufficient sample for analysis. bAs defined by the National Comprehensive Cancer Network (NCCN) risk categorization v2014. cPatients may have had more than one comorbidity. |
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CLL/SLL Starting Pack | Each pack contains four weekly wallet blister packs:
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0074-0579-28 |
Wallet containing 10 mg tablets | 14 x 10 mg tablets | 0074-0561-14 |
Wallet containing 50 mg tablets | 7 x 50 mg tablets | 0074-0566-07 |
Unit dose blister containing 10 mg tablets | 2 x 10 mg tablets | 0074-0561-11 |
Unit dose blister containing 50 mg tablet | 1 x 50 mg tablet | 0074-0566-11 |
Unit dose blister containing 100 mg tablet | 1 x 100 mg tablet | 0074-0576-11 |
Bottle containing 100 mg tablets | 28 x 100 mg tablets | 0074-0576-30 |
Bottle containing 100 mg tablets | 120 x 100 mg tablets | 0074-0576-22 |
Bottle containing 100 mg tablets | 180 x 100 mg tablets | 0074-0576-34 |
VENCLEXTA (venetoclax tablets) |
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○ fever ○ chills ○ nausea ○ vomiting ○ confusion ○ shortness of breath |
○ seizures ○ irregular heartbeat ○ dark or cloudy urine ○ unusual tiredness ○ muscle or joint pain |
Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased. Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you have side effects. When restarting VENCLEXTA after stopping for 1 week or longer, your healthcare provider may again check for your risk of TLS and change your dose. See " |
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VENCLEXTA is a prescription medicine used:
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You should not drink grapefruit juice, eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood. |
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VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility. These are not all the possible side effects of VENCLEXTA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
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Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use VENCLEXTA for a condition for which it was not prescribed. Do not give VENCLEXTA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about VENCLEXTA that is written for health professionals. |
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The 10 mg and 100 mg coated tablets also include: iron oxide yellow, polyvinyl alcohol, polyethylene glycol, talc, and titanium dioxide. The 50 mg coated tablets also include: iron oxide yellow, iron oxide red, iron oxide black, polyvinyl alcohol, talc, polyethylene glycol, and titanium dioxide. |
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Manufactured and Marketed by: AbbVie Inc. North Chicago, IL 60064 © 2016-2022 AbbVie Inc. 20070720 R1 |
Marketed by: Genentech USA, Inc. A Member of the Roche Group South San Francisco, CA 94080-4990 © 2016-2022 Genentech, Inc. |
For more information go to www.venclexta.com or call 1-800-633-9110 | |
This Medication Guide has been approved by the U.S. Food and Drug Administration. | Revised: 6/2022 |