FLASCO

New indication for VENCLEXTA(R) (venetoclax tablets)

  • FLASCO
  • December 2, 2018

On November 21, 2018, VENCLEXTA® (venetoclax tablets) was approved by the US Food and Drug
Administration (FDA) in combination with azacitidine, or decitabine, or low-dose cytarabine for the
treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or
who have comorbidities that preclude use of intensive induction chemotherapy.
This indication is approved under accelerated approval based on response rates. Continued approval for
this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
VENCLEXTA is also approved for the treatment of patients with chronic lymphocytic leukemia (CLL) or
small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior
therapy.
VENCLEXTA Access Solutions is your resource for access and reimbursement support after
VENCLEXTA is prescribed. We can help your patients by providing:
· Benefits investigations (BIs)
· Prior authorization (PA) resources
· Information about authorized specialty pharmacies (SPs) and specialty distributors
· Sample billing and coding information
· Resources for denials and appeals
· Patient assistance options
A list of authorized specialty pharmacies and specialty distributors is available at
Genentech-Access.com/ VENCLEXTA.

For more information about VENCLEXTA Access Solutions, please contact me directly, visit
Genentech-Access.com/VENCLEXTA or call (888) 249-4918.
Indications and Important Safety Information
Indications
VENCLEXTA® (venetoclax tablets) is indicated:
· For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic
lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.
· In combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly-
diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have
comorbidities that preclude use of intensive induction chemotherapy.
This indication is approved under accelerated approval based on response rates. Continued approval for
this indication may be contingent upon verification and description of clinical benefit in confirmatory
trials.

Important Safety Information
Contraindication
· Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is
contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS).
Tumor Lysis Syndrome
· Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in patients
with high tumor burden when treated with VENCLEXTA.
· In patients with CLL, with the current (5 week) dose ramp-up, TLS prophylaxis and monitoring, the rate
of TLS was 2% in the VENCLEXTA CLL monotherapy studies. The rate of TLS remained consistent with
VENCLEXTA in combination with rituximab. With a 2 to 3 week dose ramp-up and higher starting dose in
patients with CLL/SLL, the TLS rate was 13% and included deaths and renal failure.
· VENCLEXTA poses a risk for TLS at initiation and during the ramp-up phase. Changes in blood chemistries
consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the
first dose of VENCLEXTA and at each dose increase.
· Patients should be assessed for TLS risk, including evaluation of tumor burden and comorbidities, and
should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Reduced
renal function further increases the risk. Monitor blood chemistries and manage abnormalities
promptly. Interrupt dosing if needed. Employ more intensive measures (IV hydration, frequent
monitoring, hospitalization) as overall risk increases.
· Concomitant use of VENCLEXTA with strong or moderate CYP3A inhibitors or P-gp inhibitors may
increase the risk of TLS at initiation and during the ramp-up phase, and requires dose adjustment due to
increases in VENCLEXTA exposure.
Neutropenia
· In patients with CLL, Grade 3 or 4 neutropenia developed in 64% of patients and Grade 4 neutropenia
developed in 31% of patients treated with VENCLEXTA in combination with rituximab. Grade 3 or 4
neutropenia developed in 63% of patients and Grade 4 neutropenia developed in 33% of patients
treated with VENCLEXTA monotherapy. Febrile neutropenia occurred in 4% of patients treated with
VENCLEXTA in combination with rituximab and in 6% of patients treated with VENCLEXTA monotherapy.
· In patients with AML, baseline neutrophil counts worsened in 97% to 100% of patients treated with
VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine. Neutropenia can recur
with subsequent cycles of therapy.
· Monitor complete blood counts throughout the treatment period. Interrupt dosing or reduce dose for
severe neutropenia. Consider supportive measures including antimicrobials for signs of infection and use
of growth factors (e.g., G-CSF).
Immunization
· Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-
cell recovery occurs. Advise patients that vaccinations may be less effective.
Embryo-Fetal Toxicity
· VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. Advise females of
reproductive potential to avoid pregnancy during treatment.
Adverse Reactions
· In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse
reaction (≥5%) was pneumonia (9%). The most common adverse reactions (≥20%) of any grade were
neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%),
and nausea (21%).

· In patients with CLL/SLL receiving monotherapy, the most frequent serious adverse reactions (≥5%)
were pneumonia (9%), febrile neutropenia (5%), and sepsis (5%). The most common adverse reactions
(≥20%) of any grade were neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract
infection (36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletal pain (29%),
edema (22%), and cough (22%).
· In patients with AML receiving combination therapy with azacitidine, the most frequent serious
adverse reactions (≥5%) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excluding
fungal), respiratory failure, and multiple organ dysfunction syndrome. The most common adverse
reactions (≥30%) of any grade were nausea (58%), diarrhea (54%), constipation (49%), neutropenia
(49%), thrombocytopenia (49%), hemorrhage (46%), peripheral edema (46%), vomiting (40%), fatigue
(36%), febrile neutropenia (36%), rash (33%), and anemia (30%).
· In patients with AML receiving combination therapy with decitabine, the most frequent serious
adverse reactions (≥5%) were febrile neutropenia, sepsis (excluding fungal), pneumonia (excluding
fungal), diarrhea, fatigue, cellulitis, and localized infection. The most common adverse reactions (≥30%)
of any grade were febrile neutropenia (69%), constipation (62%), fatigue (62%), thrombocytopenia
(54%), abdominal pain (46%), dizziness (46%), hemorrhage (46%), nausea (46%), pneumonia (excluding
fungal) (46%), sepsis (excluding fungal) (46%), cough (38%), diarrhea (38%), neutropenia (38%), back
pain (31%), hypotension (31%), myalgia (31%), oropharyngeal pain (31%), peripheral edema (31%),
pyrexia (31%), and rash (31%).
· In patients with AML receiving combination therapy with low-dose cytarabine, the most frequent
serious adverse reactions (≥5%) were febrile neutropenia, sepsis (excluding fungal), hemorrhage,
pneumonia (excluding fungal), and device-related infection. The most common adverse reactions (≥30%)
of any grade were nausea (64%), thrombocytopenia (59%), hemorrhage (49%), febrile neutropenia
(46%), neutropenia (46%), diarrhea (44%), fatigue (44%), constipation (33%), and dyspnea (31%).
Drug Interactions
· Concomitant use with a strong or moderate CYP3A inhibitor or a P-gp inhibitor increases VENCLEXTA
exposure, which may increase VENCLEXTA toxicities, including the risk of TLS. Adjust VENCLEXTA dosage
and closely monitor patients for signs of VENCLEXTA toxicities. Resume the VENCLEXTA dosage that was
used prior to concomitant use of a strong or moderate CYP3A inhibitor or a P-gp inhibitor 2 to 3 days
after discontinuation of the inhibitor.
· Patients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain
inhibitors of CYP3A.
· Avoid concomitant use of strong or moderate CYP3A inducers.
· Avoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use is unavoidable, separate
dosing of the P-gp substrate at least 6 hours before VENCLEXTA.
· Monitor international normalized ratio (INR) closely in patients receiving warfarin.
Lactation
· Advise nursing women to discontinue breastfeeding during treatment with VENCLEXTA.

Females and Males of Reproductive Potential
· Advise females of reproductive potential to use effective contraception during treatment with
VENCLEXTA and for at least 30 days after the last dose.
· Based on findings in animals, male fertility may be compromised by treatment with VENCLEXTA.

Please see full Prescribing Information for Indication and additional Important Safety Information.

 

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