SAFETY CONSIDERATIONS

At the time of data analysis, the median duration of exposure was 22 months in the VEN+R arm compared with 6 months in the BR arm.

  • In the VEN+R arm, 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 rituximab were reported in 2% (4/194) of patients. Serious adverse reactions were reported in 46% of patients in the VEN+R arm, with the most frequent (>5%) being pneumonia (9%)
  • Discontinuation due to any adverse events occurred in 16% of patients on VEN+R and in 10% of patients on BR
  • Dose reductions due to adverse events occurred in 15% of patients in both arms
  • Dose interruptions due to adverse events occurred in 71% of patients in the VEN+R arm and in 40% of patients on BR
  • Neutropenia led to dose interruption of VENCLEXTA in 46% of patients and discontinuation in 3%, and thrombocytopenia led to discontinuation in 3% of patients
  • The MURANO trial was not designed to demonstrate a statistically significant difference in adverse reaction rates for VEN+R as compared with BR, for any specific adverse reaction or laboratory abnormality

Adverse reactions (all grades) reported in 10% of patients in the VEN+R arm in MURANO and other important adverse reactions include:

  • Blood & lymphatic system disorders: anemia (16%), thrombocytopenia (15%), febrile neutropenia (4%)
  • Gastrointestinal disorders: nausea (21%), constipation (14%), abdominal pain (13%), mucositis (10%), vomiting (8%)
  • Respiratory disorders: cough (22%)
  • General disorders & administration site conditions: fatigue (22%), pyrexia (15%)
  • Skin disorders: rash (13%)
  • Nervous system & psychiatric disorders: headache (11%), insomnia (11%)
  • Infections & infestations: pneumonia (10%)

During treatment with single-agent VENCLEXTA after completion of VEN+R combination treatment

  • The most common (all grades) adverse reactions (≥10% patients) reported were upper respiratory tract infections (21%), diarrhea (19%), neutropenia (16%), and lower respiratory tract infection (11%)
  • The most common grade 3 or 4 adverse reaction (≥2% patients) were neutropenia (12%) and anemia (3%)

Tumor Lysis Syndrome (TLS)

  • The incidence of TLS was 3% (6/194) in patients treated with VEN+R 
  • After 77/389 patients were enrolled in the study, the protocol was amended to incorporate the current TLS prophylaxis and monitoring measures 
  • All events of TLS occurred during the ramp-up period and were resolved within two days. All six patients completed the ramp-up and reached the recommended daily dose of 400 mg of VENCLEXTA 
  • No clinical TLS was observed in patients who followed the current 5-week ramp-up schedule and TLS prophylaxis and monitoring measures

For common laboratory abnormalities data, please see Table 8 in the VENCLEXTA full Prescribing Information.