Assess blood chemistry and correct pre-existing abnormalities prior to initiation of treatment:

Potassium
Uric acid
Phosphorus
Calcium
Creatinine

Considerations for TLS with VENCLEXTA

VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for tumor lysis syndrome (TLS) at initiation and during the ramp-up phase in all patients, and during reinitiation after dosage interruption (see dose modification and interruption information)
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
The risk of TLS is a continuum based on multiple factors, particularly reduced renal function (CLcr <80 mL/min) and tumor burden; splenomegaly may also increase the risk
Consider all patient comorbidities before final determination of prophylaxis and monitoring schedule
The risk of TLS may decrease as tumor size decreases

Reassess the risk of TLS when reinitiating VENCLEXTA after a dosage interruption lasting more than 1 week during the ramp-up phase, or more than 2 weeks after completion of ramp-up. Institute prophylaxis and monitoring as needed.

Interact with the Tumor Burden Assessment tutorial to explore the relationship between lymph node (LN) size, absolute lymphocyte count (ALC), and TLS prophylaxis and monitoring.

3 STEPS: ASSESS, PREPARE, INITIATE

Chart for tumor burden risk assessment, preparation and monitoring

*1.5-2 L of water (~56 ounces) should be consumed every day starting at least 2 days before the first dose and throughout the ramp-up phase, especially the first day of each dose increase. Administer intravenous hydration for any patient who cannot tolerate oral hydration.
^†Start allopurinol or xanthine oxidase inhibitor 2 to 3 days prior to initiation of VENCLEXTA.
^‡Evaluate blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine); review in real time.
^§For patients at risk of TLS, monitor blood chemistries at 6 to 8 hours and at 24 hours at each subsequent dose ramp-up.

TLS=tumor lysis syndrome; CLcr=creatinine clearance.

Download a copy of the Treatment Guide ⬇︎

Tumor Burden Assessment Tutorial

Enhance your understanding of TLS risk assessment for patients initiating VENCLEXTA regimens for CLL

Complete the lymph node size and ALC selections below, hit "assess," and the tutorial will classify the tumor burden assessment level, as well as provide helpful suggestions regarding prophylaxis, blood chemistry monitoring setting, and frequency of assessments based on the VENCLEXTA package insert.

Select a lymph node size range and ALC:

Lymph node size:*

All <5 cm Any 5 cm to <10 cm Any ≥10 cm

ALC:*

<25 x 10⁹/L >25 x 10⁹/L

These classifications are provided to help inform healthcare practitioners of information within the VENCLEXTA package insert. This is not medical advice or a determination of tumor lysis syndrome risk.

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Both our staff and our patients need to know and understand…why we are doing what we’re doing.
-Christina Patterson, PA-C, Cancer Care Associates of York, York, PA

See Christina Patterson, PA-C, Cancer Care Associates of York, discuss how to prepare patients and staff for the VENCLEXTA initiation process.

Watch video

Video thumbnail - Christina Patterson Patient and Staff Preparation

Initiation

Find resources to help start your patients on VENCLEXTA

Explore Starting VENCLEXTA

Treatment resources

Get treatment and drug interaction guides

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Safety data

See VENCLEXTA’s well-studied safety profile for patients with previously untreated and R/R CLL¹

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Indication

VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

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 treated with VENCLEXTA.
VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS at initiation and during the ramp-up phase in all patients, and during reinitiation after dosage interruption in patients with CLL/SLL. 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. TLS, including fatal cases, has been reported after a single 20 mg dose.
In patients with CLL/SLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent with VENCLEXTA in combination with obinutuzumab or 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.
The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy. Splenomegaly may also increase the risk of TLS in patients with CLL/SLL.
Assess all patients for risk and provide appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Monitor blood chemistries and manage abnormalities promptly. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed; when restarting VENCLEXTA follow dose modification guidance in the Prescribing Information.
Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3A inhibitors increases venetoclax exposure, which may increase the risk of TLS at initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction.

Neutropenia

In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients when treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients.
Monitor complete blood counts. Interrupt dosing for severe neutropenia and resume at same or reduced dose. Consider supportive measures including antimicrobials and growth factors (e.g., G-CSF).

Infections

Fatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA. Monitor patients for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infection until resolution and resume at same or reduced dose.

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 use effective contraception during treatment and for 30 days after the last dose.

Increased Mortality in Patients with Multiple Myeloma when VENCLEXTA is Added to Bortezomib and Dexamethasone

In a randomized trial (BELLINI; NCT02755597) in patients with relapsed or refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plus dexamethasone, a use for which VENCLEXTA is not indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with VENCLEXTA in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials.

Adverse Reactions

In patients with CLL receiving combination therapy with obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% each). The most common adverse reactions (≥20%) of any grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). Fatal adverse reactions that occurred in the absence of disease progression and with onset within 28 days of the last study treatment were reported in 2% (4/212) of patients, most often from infection.
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%), and nausea (21%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of the last VENCLEXTA treatment and/or 90 days of the last rituximab were reported in 2% (4/194) of patients.
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%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of venetoclax treatment were reported in 2% of patients in the VENCLEXTA monotherapy studies, most often (2 patients) from septic shock.

Drug Interactions

Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitor increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including the risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage and monitor more frequently for adverse reactions. Resume the VENCLEXTA dosage that was used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3A 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.
Monitor international normalized ratio (INR) more frequently in patients receiving warfarin.
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.

Lactation

Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for 30 days after the last dose.
Based on findings in animals, VENCLEXTA may impair male fertility.

Hepatic Impairment

Reduce the dose of VENCLEXTA for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more frequently for adverse reactions. No dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

Please see full Prescribing Information.

VENCLEXTA^®, VENCOMPASS^® and their designs are registered trademarks of AbbVie Inc.
GAZYVA^® is a registered trademark of Genentech, Inc.

- VENCLEXTA Prescribing Information.
  
  VENCLEXTA Prescribing Information.
- Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236.
  
  Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236.
- GAZYVA Prescribing Information, January 2021.
  
  GAZYVA Prescribing Information, January 2021.
- Data on file, AbbVie Inc. ABVRRTI69608.
  
  Data on file, AbbVie Inc. ABVRRTI69608.
- Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23)(suppl):2225-2236.
  
  Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23)(suppl):2225-2236.
- Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120.
  
  Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120.
- Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12)(suppl):1107-1120.
  
  Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12)(suppl):1107-1120.
- Data on file, AbbVie Inc. ABVRRTI69609.
  
  Data on file, AbbVie Inc. ABVRRTI69609.
- Seymour JF, Kipps TJ, Eichhorst B, et al. Four-year analysis of MURANO study confirms sustained benefit of time-limited venetoclax-rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.
  
  Seymour JF, Kipps TJ, Eichhorst B, et al. Four-year analysis of MURANO study confirms sustained benefit of time-limited venetoclax-rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.
- Data on file, AbbVie Inc. ABVRRTI74117.
  
  Data on file, AbbVie Inc. ABVRRTI74117.
- Al-Sawaf O, Zhang C, Robrecht S, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 5-year results of the randomized CLL14 study. Abstract presented at: European Hematology Association Congress 2022; June 9-17, 2022.
  
  Al-Sawaf O, Zhang C, Robrecht S, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 5-year results of the randomized CLL14 study. Abstract presented at: European Hematology Association Congress 2022; June 9-17, 2022.
- Data on file, AbbVie Inc. ABVRRTI71322.
  
  Data on file, AbbVie Inc. ABVRRTI71322.
- Owen C, Christofides A, Johnson N, Lawrence T, MacDonald D, Ward C. Use of minimal residual disease assessment in the treatment of chronic lymphocytic leukemia [published online ahead of print May 16, 2017]. Leuk Lymphoma. 2017;58(12):2777-2785.
  
  Owen C, Christofides A, Johnson N, Lawrence T, MacDonald D, Ward C. Use of minimal residual disease assessment in the treatment of chronic lymphocytic leukemia [published online ahead of print May 16, 2017]. Leuk Lymphoma. 2017;58(12):2777-2785.
- Thompson PA, Wierda WG. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL. Blood. 2016;127(3):279-286.
  
  Thompson PA, Wierda WG. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL. Blood. 2016;127(3):279-286.
- US Food and Drug Administration. Hematologic malignancies: regulatory considerations for use of minimal residual disease in development of drug and biological products for treatment. Guidance for industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/hematologic-malignancies-regulatory-considerations-use-minimal-residual-disease-development-drug-and. January 2020. Accessed February 28, 2020.
  
  US Food and Drug Administration. Hematologic malignancies: regulatory considerations for use of minimal residual disease in development of drug and biological products for treatment. Guidance for industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/hematologic-malignancies-regulatory-considerations-use-minimal-residual-disease-development-drug-and. January 2020. Accessed February 28, 2020.
- Seymour JF, Kipps TJ, Eichhorst B, et al. Four-year analysis of MURANO study confirms sustained benefit of time-limited venetoclax–rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.
  
  Seymour JF, Kipps TJ, Eichhorst B, et al. Four-year analysis of MURANO study confirms sustained benefit of time-limited venetoclax–rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.
- Greer JA, Amoyal N, Nisotel L, et al. A systematic review of adherence to oral antineoplastic therapies. Oncologist. 2016;21(3):354-376.
  
  Greer JA, Amoyal N, Nisotel L, et al. A systematic review of adherence to oral antineoplastic therapies. Oncologist. 2016;21(3):354-376.
- Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin. 2009;59(1):56-66.
  
  Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin. 2009;59(1):56-66.
- Giacomini KM, Huang S-M, Tweedie DJ, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215-236.
  
  Giacomini KM, Huang S-M, Tweedie DJ, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215-236.
- Wessler JD, Grip LT, Mendell J, Giugliano RP. The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol. 2013;61(25):2495-2502.
  
  Wessler JD, Grip LT, Mendell J, Giugliano RP. The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol. 2013;61(25):2495-2502.
- CRESEMBA Prescribing Information. December 2019.
  
  CRESEMBA Prescribing Information. December 2019.
- Drug development and drug interactions: table of substrates, inhibitors and inducers. US Food and Drug Administration website. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#cypEnzymes. Updated November 14, 2017. Accessed March 11, 2021.
  
  Drug development and drug interactions: table of substrates, inhibitors and inducers. US Food and Drug Administration website. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#cypEnzymes. Updated November 14, 2017. Accessed March 11, 2021.

Tumor burden assessment, prophylaxis, and monitoring for TLS1