SUMMARY  

• DARZALEX is not approved by the regulatory agencies for the treatment of patients with Waldenström Macroglobulinemia (WM). Johnson & Johnson does not recommend the use of DARZALEX in a manner that is inconsistent with the approved labeling.
• Castillo et al (2020)¹ published results of a phase 2, multicenter, prospective study that evaluated the efficacy of DARZALEX monotherapy in previously treated patients with WM. The overall response rate (ORR) was 23%. The most common any grade treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (n=5), infusion reactions (n=5), lymphopenia (n=3), and neutropenia (n=2). The study was terminated due to futility.
• Jhaveri et al (2025)² presented a case report of a 66 year old male with WM with concomitant cardiac amyloidosis and non-amyloid disease in the gastrointestinal tract.
  • The patient received 6 cycles of bendamustine and rituximab; he experienced a minor response, followed by hospitalization due to worsening cardiac function.
  • The patient was then treated with 2 cycles of DARZALEX plus cyclophosphamide, bortezomib, and dexamethasone (dara-CyBorD) without adequate response.
  • Treatment plan is to commence zanubrutinib for his underlying IgM amyloidosis and lymphoplasmacytic lymphoma while awaiting advanced cardiac care.

clinical data

Castillo et al (2020)¹ published results of a phase 2, multicenter, prospective study evaluating the efficacy of DARZALEX monotherapy in previously treated patients with WM.  

Study design/Methods

• Key inclusion criteria: meet clinicopathologic criteria for WM³, require treatment according to consensus guidelines⁴, and received ≥1 prior treatment regimen.
• Key exclusion criteria: infections with Human Immunodeficiency Virus (HIV), hepatitis B or hepatitis C, or central nervous system involvement.
• Patients received DARZALEX 16 mg/kg intravenously (IV) once weekly for 8 doses (cycles 1 and 2), once every 2 weeks for 8 doses (cycles 3-6), and once every 4 weeks for 12 doses (cycles 7-18), for a total of 28 doses over 18 months.
• Bone marrow aspirations, biopsies, and computed tomography scans (if extramedullary disease was present at baseline) were repeated after completing cycles 6 and 18.
• Primary endpoint: overall response rate (ORR) using criteria from the Sixth International Workshop on WM.
• Secondary endpoints: major response, progression-free survival (PFS), and drug safety.

Results

Patient Characteristics

• Between July 2018 and May 2019, 13 patients with previously treated WM were enrolled.
• Select baseline characteristics are shown in Table: Select Baseline Characteristics.
• Indications for treatment initiation were constitutional symptoms (n=6), peripheral neuropathy (n=6), anemia (n=5), hyperviscosity (n=2), and extramedullary disease (n=1).

Efficacy

• The median number of cycles of DARZALEX received was 2 (range, 0-18).
• At best response, a total of 2 patients attained partial response (PR), 1 attained minor response, 3 had stable disease (SD), and 7 experienced progressive disease (PD). The ORR was 23%, the major response rate was 15%, and the clinical benefit was 54%.
• Two patients completed the planned 18 cycles of therapy, both of which had only 1 prior line of therapy; 1 patient attained PR and 1 attained SD at the end of cycle 18.
• DARZALEX was stopped prematurely in 11 patients due to disease progression (n=9) and lack of response (n=2).
• Median PFS was 2 months (95% confidence interval [CI], 1-4).

Safety

• Safety events are summarized in Table: Summary of Treatment-Emergent Adverse Events (TEAEs).
• There was one death within 20 days of study enrollment due to rapid disease progression. This patient had progressed on ibrutinib which was stopped 48 hours before starting DARZALEX.
• The study was terminated because of futility (suboptimal depth of response and durability in the first 13 patients).

Literature Search

A literature search of MEDLINE^®, Embase, BIOSIS Previews^®, and Derwent Drug File (and other resources, including internal/external databases) was conducted on 16 December 2025.