GADOLIN safety information

INVESTIGATOR-REPORTED ADVERSE REACTIONS

Adverse reactions (incidence ≥10% and ≥2% greater in the GAZYVA arm) in patients with relapsed or refractory NHL 1

GAZYVA GADOLIN Investigator Reported Adverse Reactions Chart

GAZYVA monotherapy investigator-reported adverse reactions 1

  • During GAZYVA monotherapy (158 patients), adverse reactions in ≥10% of patients included upper and lower respiratory tract infections, cough, neutropenia, musculoskeletal pain, fatigue, diarrhea, rash, and urinary tract infection
  • The most common adverse reactions (incidence ≥20%) in GAZYVA recipients included infusion-related reactions, fatigue, neutropenia, cough, upper respiratory tract infections, and musculoskeletal pain

Adverse events leading to treatment withdrawal 2

  • Discontinuation of any study drug due to adverse reactions occurred in 20% of the GAZYVA + bendamustine followed by GAZYVA monotherapy arm vs 17% in the bendamustine-only arm

The GADOLIN study evaluated safety in 407 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

New or worsening laboratory abnormalities (incidence ≥10% and ≥2% greater in the GAZYVA arm 1,b in patients with relapsed or refractory NHL

GAZYVA GADOLIN Laboratory Abnormalities Chart

GAZYVA monotherapy hematologic laboratory abnormalities 1

  • Adverse reactions in ≥10% of patients included upper and lower respiratory tract infections, neutropenia, musculoskeletal pain, fatigue, diarrhea, nausea, and urinary tract infection
  • New or worsening Grade 3 or 4 abnormalities included neutropenia in 25% of patients (Grade 4, 10%) and lymphopenia in 23% (Grade 4, 5%)

Hematologic laboratory abnormalities in the GAZYVA treated arm 1

  • The most frequently reported hematologic Grade 3-4 laboratory abnormalities were lymphopenia (92%), neutropenia (53%), and leukopenia (47%)

Non-hematologic laboratory abnormalities in the GAZYVA treated arm 1

  • The most frequently reported non-hematologic Grade 3-4 laboratory abnormalities were hypophosphatemia (8%), hypocalcemia (3%), hyperkalemia (3%), ALT/SGPT increased (2%), and hyperbilirubinemia (2%)

The GADOLIN study evaluated safety in 407 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-Related Reactions: Overall, 67% of patients in the GADOLIN study experienced an IRR (all grades) during treatment with GAZYVA in combination with bendamustine. The incidence of Grade 3 to 4 IRRs in GADOLIN was 11%. In Cycle 1, the incidence of IRRs (all grades) was 53% in patients receiving GAZYVA in combination with bendamustine of which 34 (9%) were Grade 3 to 4 in severity. In patients receiving GAZYVA in combination with bendamustine, the incidence of IRRs was highest on Day 1 (37%), and gradually decreased on Days 2, 8 and 15 (23%, 6% and 4%, respectively). During Cycle 2, the incidence of IRRs was 24% in patients receiving GAZYVA in combination with bendamustine and decreased with subsequent cycles. During GAZYVA monotherapy in GADOLIN, IRRs (all grades) were observed in 8% of patients. One Grade 3 and no Grade 4 IRRs were reported during GAZYVA monotherapy. Overall, 2% of patients in GADOLIN experienced an IRR leading to discontinuation of GAZYVA.

Neutropenia: The incidence of neutropenia in GADOLIN was higher in the GAZYVA plus bendamustine arm (37%) compared to the arm treated with bendamustine alone (30%). Cases of prolonged neutropenia (3%) and late onset neutropenia (8%) were also reported in the GAZYVA plus bendamustine arm. The incidence of neutropenia was higher during treatment with GAZYVA in combination with bendamustine (30%) compared to the GAZYVA monotherapy treatment phase (13%).

Infections: The incidence of infection in GADOLIN was 68% in the GAZYVA plus bendamustine arm and 59% in the bendamustine arm, with Grade 3 to 4 events reported in 20% and 16%, respectively. Fatal events were reported in 3% of patients in the GAZYVA plus bendamustine arm and 3% 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 (25%). The incidence of hemorrhagic events in GAZYVA plus bendamustine treated patients compared to bendamustine alone was 12% and 11%, respectively. Grade 3 to 4 hemorrhagic events were similar in both treatment arms (4% in the GAZYVA plus bendamustine arm and 2% in the bendamustine arm).

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

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 (44% vs 30%). 

Gastrointestinal Perforation: Cases of gastrointestinal 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.