Treatment of CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma With Bruton Tyrosine Kinase Inhibitor Zanubrutinib

A Phase 2, Single-Arm, Open-Label, Multicenter Study of the Bruton Tyrosine Kinase Inhibitor Zanubrutinib in Patients With CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma

The goal of this clinical trial was to evaluate whether zanubrutinib can effectively treat adults with CD79B-mutant relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Participants received zanubrutinib as monotherapy, underwent regular disease assessments to evaluate treatment response, and were monitored for safety and side effects throughout the study.

Inclusion Criteria

1. Participants had histologically confirmed diffuse large B-cell lymphoma, based on the World Health Organization 2008 classification of tumors of hematopoietic and lymphoid tissue.

2. Participants had a positive CD79B gene mutation, as confirmed by a central laboratory.

3. Participants had previously received at least one line of adequate systemic therapy for diffuse large B-cell lymphoma, defined as anti-CD20 antibody-based chemoimmunotherapy administered for at least two consecutive cycles, unless disease progression occurred before completion of Cycle 2.

4. Participants had relapsed or refractory disease prior to study entry, defined as either:

   1. Recurrent disease after achieving disease remission, defined as a complete response or partial response, at the completion of the most recent treatment regimen; or
   2. Stable disease or progressive disease at the completion of the most recent treatment regimen.

5. Participants were ineligible for high-dose therapy and stem cell transplantation, defined as meeting at least one of the following criteria:

   a. Presence of significant organ dysfunction, such as:

   1. Left ventricular ejection fraction less than 50 percent as measured by echocardiogram or multiple gated acquisition scan;
   2. Diffusing capacity of the lung for carbon monoxide less than 60 percent of the predicted value as measured by pulmonary function testing; or
   3. Creatinine clearance less than 70 milliliters per minute as demonstrated by nuclear medicine scan or 24-hour urine collection; or comorbid conditions that precluded the use of high-dose therapy and stem cell transplantation due to an unacceptable risk of treatment-related morbidity.

   b. Failure to achieve a complete response or partial response following salvage therapy.

   c. Failure to collect stem cells or inability to undergo stem cell collection, as assessed by the investigator.

Exclusion Criteria

1. Participants had non-Hodgkin lymphoma other than classical histology diffuse large B-cell lymphoma (not otherwise specified), including but not limited to:

   1. Diffuse large B-cell lymphoma transformed from indolent lymphomas
   2. Primary mediastinal (thymic) large B-cell lymphoma
   3. Primary cutaneous diffuse large B-cell lymphoma
   4. Primary effusion lymphoma
   5. Central nervous system lymphoma

2. Participants had a history of allogeneic stem cell transplantation or chimeric antigen receptor T-cell therapy.

3. Participants had prior exposure to a Bruton's tyrosine kinase inhibitor.

4. Participants had received any of the following treatments within the specified timeframe prior to the first dose of study drug:

   1. Corticosteroids administered with antineoplastic intent within two weeks prior to study treatment. A short course (seven days or fewer) of systemic corticosteroids at doses of 20 milligrams per day or less of prednisone equivalent for control of lymphoma-related symptoms was permitted prior to enrollment, provided the corticosteroids were tapered off within five days after initiation of study treatment.
   2. Chemotherapy or radiotherapy within two weeks.
   3. Monoclonal antibody therapy within two weeks.
   4. Investigational therapy within two weeks.
   5. Chinese patent medicine administered with antineoplastic intent within two weeks.

5. Participants had a history of other active malignancies within two years prior to study entry, with the exception of:

   1. Adequately treated carcinoma in situ of the cervix;
   2. Localized basal cell carcinoma or squamous cell carcinoma of the skin; or
   3. A previous malignancy that was confined and treated locally (by surgery or other modality) with curative intent.

Note: Other protocol-defined inclusion and exclusion criteria may have applied.