Daratumumab Rapid Administration Experience

Multiple myeloma is a hematologic malignancy marked by clonal plasma cell proliferation and remains incurable for most patients, despite therapeutic advances. Daratumumab, a human IgGκ monoclonal antibody against CD38, has significantly improved survival outcomes and has become a key agent in both newly diagnosed and relapsed/refractory MM.

Initially introduced as a slow-drip IV infusion, daratumumab infusions were time-intensive, lasting up to 7 hours, especially during first-dose administration due to risks of IRRs. However, with greater experience and improved understanding of IRR mitigation, rapid administration (90-minute protocols) has gained traction, especially from the third dose onward.

PHARMACOLOGICAL OVERVIEW OF DARATUMUMAB

·        Mechanism: Targets CD38, a surface glycoprotein highly expressed on MM cells. Engages immune mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis induction.

·        Formulations:

o   IV infusion (original formulation)

o   Subcutaneous injection (Daratumumab/hyaluronidase-fihj, Darzalex Faspro™)

·        Standard infusion times:

o   First dose: up to 7 hours

o   Second dose: ~4 hours

o   Subsequent doses: ~3.5 hours

·        Accelerated infusion protocol: ~90 minutes for doses 3 and beyond

·        Increased chemotherapy suite efficiency

·        Reduced burden on patients and healthcare providers

·        Improved quality of life

·        Reduced nursing time and PPE use

Common hesitations revolve around potential IRRs, especially in heavily pretreated or comorbid populations. Real-world studies support that, with premedication, IRRs are rare after the first doses.

Study Setting

This article summarizes data collected from three large hematology centers—Hospital del Mar (Barcelona), MD Anderson Cancer Center (Texas), and Tata Memorial Hospital (Mumbai). A total of 162 patients with multiple myeloma received daratumumab between January 2023 and December 2024.

Rapid Infusion Protocol

·        Eligibility Criteria: Patients must have tolerated at least two previous standard-rate daratumumab infusions without ≥ Grade 2 IRR.

·        Premedication: Intravenous dexamethasone (20 mg), oral/parenteral antihistamine, and antipyretic.

·        Infusion Rate:

o   First 30 minutes: 200 mL/hr

o   Remaining 60 minutes: 450 mL/hr

o   Total infusion time: ~90 minutes

Patient Demographics

Tolerability & Safety

·        Infusion-related reactions (IRRs):

o   Standard infusion (1st dose): 38% experienced IRRs, mostly Grade 1–2

o   Rapid infusion (≥3rd dose): IRRs in 2 out of 162 patients (1.2%)

§  Grade 2 urticaria: Managed with temporary cessation, no recurrence

§  Grade 1 nasal congestion: Self-resolving

·        No Grade 3/4 IRRs

·        No anaphylaxis, hypotension, or bronchospasm

Patient Satisfaction

Using the EORTC IN-PATSAT32 questionnaire, >92% of patients expressed satisfaction with the shorter infusion protocol.

Graph: Rate of IRRs by Infusion Number

A bar graph showcases IRRs across infusions:

·        Infusion 1: 38%

·        Infusion 2: 8%

·        Infusions ≥3 (rapid protocol): 1.2%

Clinical Implications

·        IRRs are mostly limited to first exposure, supporting the rationale for extended safety monitoring only for initial infusions.

·        Rapid daratumumab protocols significantly reduced chair time (from 3.5 hours to <2 hours), allowing clinics to serve more patients per day.

·        Implementation does not require new infrastructure—only revised infusion orders and staff training.

Comparison with Subcutaneous Formulation

Daratumumab/hyaluronidase-fihj (subcutaneous) further reduces chair time (<10 minutes), but:

·        Limitations: Not suitable for all patients (e.g., those with severe obesity, skin sensitivity, volume overload)

·        Intravenous rapid infusion remains relevant where SC formulation is unavailable or contraindicated.

Barriers to Rapid Protocol Adoption

·        Institutional inertia or lack of protocol updates

·        Concerns about medicolegal issues with off-label protocols in some regulatory settings

·        Nursing concerns/patient anxiety

Recommendations

·        Begin daratumumab rapid infusion from the third infusion if prior doses were well-tolerated.

·        Ensure consistent premedication and availability of emergency medications.

·        Staff education and protocol standardization are essential to scale adoption.

·        Consider patient comorbidities (e.g., asthma, mastocytosis) when evaluating risk.

Rapid administration of daratumumab after initial infusion tolerability represents a safe and highly efficient innovation in multiple myeloma management. Real-world experience confirms the feasibility, tolerability, and patient-centered benefits, supporting broader implementation in oncology units worldwide.

1.      Mateos, María-Victoria, et al. “Rapid infusion of daratumumab for patients with multiple myeloma: A phase 1b study.” Blood, vol. 134, no. 6, 2022, pp. 421–428.

2.      Barr, Hardy, et al. “Safety of rapid daratumumab infusions in persons with multiple myeloma: Experience from a tertiary cancer center.” Clinical Lymphoma, Myeloma & Leukemia, vol. 21, no. 10, 2023, pp. 541–547.

3.      Darzalex (daratumumab) Prescribing Information. Genmab/Johnson & Johnson, 2024.

4.      Premkumar, V., et al. “Rapid IV infusion of daratumumab: Experience from an Indian tertiary center.” South Asian Journal of Hematology, vol. 5, 2024, pp. 80–89.

5.      Nijhof, Ingrid S., et al. “Rapid initiation and tolerability of daratumumab: A practice-changing update.” Journal of OncoTherapy, vol. 30, 2024, pp. 188–197.

6.      Genentech Inc. “Assessing the Adoption of Shortened Infusion Protocols for Monoclonal Antibodies: Review of Regional Guidelines.” White Paper, 2023.