This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.
This open-label, randomized study compared the efficacy and safety of the Bruton's Tyrosine Kinase (BTK) inhibitors BGB-3111 and ibrutinib in participants with Waldenström's Macroglobulinemia who require therapy. Participants had baseline bone marrow samples assayed for sequencing of the MYD88 gene. 201 participants with the MYD88 mutation were enrolled and randomized to receive 160 mg BGB-3111 orally twice per day (PO BID) (treatment Arm A) or to receive 420mg ibrutinib orally once per day (PO QD) (treatment Arm B) until disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
201
Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC)
Percentage of participants with CR, defined as normal serum immunoglobulin M (IgM) levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, or VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values.
Time frame: Up to approximately 2 years and 7 months
Percentage of Participants Achieving Major Response Rate (MRR) as Assessed by IRC
MRR defined as the percentage of participants achieving a best response of response of CR, defined as normal serum IgM levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values or partial response (PR) defined as ≥50% reduction of serum IgM from baseline.
Time frame: Up to approximately 2 years and 7 months
Duration of Response (DOR) as Assessed by IRC
DOR defined as the time from first determination of response (CR, VGPR or PR) until first documentation of progression or death, whichever comes first. CR is defined as normal serum IgM levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, VGPR, is defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values or partial response (PR) is defined as ≥50% reduction of serum IgM from baseline.
Time frame: Up to approximately 2 years and 7 months
DOR as Assessed by IRC: Event -Free Rate
Estimated percentage of participants who were event-free based on Kaplan-Meier method.
Time frame: 12 and 18 months from the date of randomization (up to approximately 2 years and 7 months)
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Percentage of Participants Achieving Either CR or VGPR in as Assessed by the Investigator
Percentage of participants with CR, defined as normal serum IgM levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at Baseline, or VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values.
Time frame: Up to approximately 5 years and 5 months
DOR as Assessed by the Investigator
DOR is defined as the time from first determination of response (CR, VGPR or PR) until first documentation of progression or death, whichever comes first
Time frame: Up to approximately 5 years and 5 months
DOR as Assessed by the Investigator: Event-Free Rate
Estimated percentage of participants who were event-free based on Kaplan-Meier method.
Time frame: 24,36 and 48 months from the date of randomization (up to approximately 5 years and 5 months)
Progression Free Survival (PFS) as Assessed by the IRC
PFS as assessed by the IRC, defined as time from randomization to the first documentation of progression (per modified International Workshop on Waldenström macroglobulinemia \[IWWM criteria\]) or death, whichever occurs first
Time frame: Up to approximately 2 years and 7 months
PFS as Assessed by IRC: Event-Free Rate
Estimated percentage of participants who were event-free based on Kaplan-Meier method
Time frame: 12 and 18 months from the date of randomization (up to approximately 2 years and 7 months)
PFS as Assessed by the Investigator
PFS as assessed by the Investigator, defined as time from randomization to the first documentation of progression (per modified IWWM criteria) or death, whichever occurs first.
Time frame: Up to approximately 5 years and 5 months
PFS as Assessed by the Investigator: Event-Free Rate
Percentage of participants who were event-free based on Kaplan-Meier method.
Time frame: 24,36 and 48 months from the date of randomization (up to approximately 5 years and 5 months)
Percentage of Participants With Resolution of All Treatment-precipitating Symptoms
Time frame: Up to approximately 5 years and 5 months
Percentage of Participants With an Anti-Lymphoma Effect
Anti-Lymphoma Effect is defined as any reduction in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or splenomegaly by CT scan, at any time during the course of study treatment.
Time frame: Up to approximately 5 years and 5 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to approximately 5 years and 5 months