GADOLIN safety information

INVESTIGATOR-REPORTED ADVERSE REACTIONS IN NHL

GAZYVA GADOLIN Investigator Reported Adverse Reactions Chart

GAZYVA monotherapy investigator-reported adverse reactions 1

  • The most common Grade 3-4 adverse reactions were neutropenia (10%), and anemia, febrile neutropenia, thrombocytopenia, sepsis, upper respiratory tract infection, and urinary tract infection (all at 1%)
  • The most common adverse reactions were cough (15%), upper respiratory tract infections (12%), neutropenia (11%), sinusitis (10%), diarrhea (8%), infusion-related reactions (8%), nausea (8%), fatigue (8%), bronchitis (7%), arthralgia (7%), pyrexia (6%), nasopharyngitis (6%), and urinary tract infections (6%)

Adverse events leading to treatment withdrawal 2

  • 11.3% in the GAZYVA + bendamustine followed by GAZYVA monotherapy arm vs 15.7% in the bendamustine-alone arm

The GADOLIN study evaluated safety in 392 patients with relapsed or refractory NHL, including follicular lymphoma (81%), small lymphocytic lymphoma, and marginal zone lymphoma. In the population of patients with follicular lymphoma, the profile of adverse reactions was consistent with the overall NHL population.

LABORATORY ABNORMALITIES IN NHL

GAZYVA GADOLIN Laboratory Abnormalities Chart

GAZYVA monotherapy hematological laboratory abnormalities 1

  • The most frequently reported hematological Grade 3-4 laboratory abnormalities were lymphopenia (52%), neutropenia (27%), leukopenia (20%), and thromobocytopenia (4%)
  • The most frequently reported hematological laboratory abnormalities were lymphopenia (80%), leukopenia (63%), low hemoglobin (50%), neutropenia (46%), and thrombocytopenia (35%)

GAZYVA monotherapy chemistry laboratory abnormalities 1

  • The most frequently reported chemistry Grade 3-4 laboratory abnormalities were hypophosphatemia (5%), hyponatremia (3%), and decreased creatinine clearance (1%)
  • The most frequently reported chemistry laboratory abnormalities were elevated creatinine (69%), decreased creatinine clearance (43%), hypophosphatemia (25%), AST/SGOT increased (24%) and ALT/SGPT increased (21%)

The GADOLIN study evaluated safety in 392 patients with relapsed or refractory NHL, including follicular lymphoma (81%), small lymphocytic lymphoma, and marginal zone lymphoma. In the population of patients with follicular lymphoma, the profile of adverse reactions was consistent with the overall NHL population.

Select GADOLIN trial safety information

Adverse reactions for GAZYVA + bendamustine followed by GAZYVA monotherapy vs bendamustine

Infusion Reactions: Overall, 69% of patients in the GADOLIN study experienced an infusion reaction (all grades) during treatment with GAZYVA in combination with bendamustine. The incidence of Grade 3 to 4 infusion reactions was 11%. In Cycle 1, the incidence of infusion reactions (all grades) was 55% in patients receiving GAZYVA in combination with bendamustine with Grade 3 to 4 infusion reactions reported in 9%. In patients receiving GAZYVA in combination with bendamustine, the incidence of infusion reactions was highest on Day 1 (38%), and gradually decreased on Days 2, 8 and 15 (25%, 7% and 4%, respectively). During Cycle 2, the incidence of infusion reactions was 24% in patients receiving GAZYVA in combination with bendamustine and decreased with subsequent cycles. During GAZYVA monotherapy in GADOLIN, infusion reactions (all grades) were observed in 8% of patients and no Grade 3 or 4 infusion reactions were reported. Overall, 2% of patients in GADOLIN experienced an infusion reaction leading to discontinuation of GAZYVA.

Neutropenia: The incidence of neutropenia in GADOLIN was higher in the GAZYVA plus bendamustine arm (38%) compared to the arm treated with bendamustine alone (32%). Cases of prolonged neutropenia (3%) and late onset neutropenia (7%) were also reported in the GAZYVA plus bendamustine arm. The incidence of neutropenia was higher during treatment with GAZYVA in combination with bendamustine (31%) compared to the GAZYVA monotherapy treatment phase (12%).

Infections: The incidence of infection in GADOLIN was 66% in the GAZYVA plus bendamustine arm and 56% in the bendamustine arm, with Grade 3 to 4 events reported in 16% and 14%, respectively. Fatal events were reported in 3% of patients in the GAZYVA plus bendamustine arm and 4% in the bendamustine arm.

Thrombocytopenia: The incidence of thrombocytopenia in GADOLIN was lower in the GAZYVA plus bendamustine arm (15%) compared to the arm treated with bendamustine alone (24%). The incidence of hemorrhagic events in GAZYVA plus bendamustine treated patients compared to bendamustine alone was 11% and 10%, respectively. Grade 3 to 4 hemorrhagic events were similar in both treatment arms (5% in the GAZYVA plus bendamustine arm and 3% in the bendamustine arm).

Tumor Lysis Syndrome: The incidence of Grade 3 or 4 tumor lysis syndrome in GADOLIN was 0.5% in the GAZYVA plus bendamustine treated arm.

Musculoskeletal Disorders: Adverse reactions related to musculoskeletal disorders (all events from the body system), including pain, have been reported in the GAZYVA plus bendamustine treated arm with higher incidence than in the bendamustine alone arm (41% vs. 29%).

Gastro-Intestinal Perforation: Cases of gastro-intestinal perforation have been reported in patients receiving GAZYVA, mainly in NHL.

Worsening of Pre-existing Cardiac Conditions: Fatal cardiac events have been reported in patients treated with GAZYVA.