SUMMARY

• Janssen does not recommend the use of DARZALEX in a manner that is inconsistent with the approved labeling.
• Kastritis et al (2024)¹ presented results from an ongoing, phase 2, open-label, multicenter, European Myeloma Network (EMN) 22 study evaluating the efficacy and safety of DARZALEX/DARZALEX FASPRO monotherapy in patients (N=40) with stage 3B newly diagnosed AL amyloidosis. At a median follow-up duration of 10.3 months, the overall response rate (ORR) was 77.5% and overall survival (OS) rates at 6- and 12-month were 65% (95% confidence interval [CI], 48.2-77.6) and 45.0% (95% CI, 29.3-59.5), respectively. At least one serious treatment emergent adverse event (TEAE) was reported by 32 patients (80%), and fatal serious adverse events (SAEs) were reported by 17 patients (42.5%).
• Rabajoli et al (2023)² presented the results from a real-life, long-term experience that evaluated DARZALEX monotherapy in patients (N=17) with AL amyloidosis. At the end of a mean follow-up of 30 months, 5 patients had persistent hematological and renal response. Two patients died due to coronavirus disease 2019 (COVID-19) infection and cardiovascular disease, respectively.
• Staron et al (2023)³ presented results from a prospective study that evaluated the rates of undetectable minimal residual disease (MRD) achievement in patients (N=66) treated with DARZALEX, and rates of MRD clearance and resurgence both during and after completion of DARZALEX therapy for AL amyloidosis. A total of 38%, 46%, and 41% of patients were MRD-negative after <12, 12-23, and 24 cycles of DARZALEX monotherapy. Rates of MRD clearance during and after completion of DARZALEX therapy for AL amyloidosis were 20% and 9%, respectively; rate of MRD resurgence after completion of DARZALEX therapy for AL amyloidosis was 9%.
• Other relevant literature has been identified in addition to the data summarized above and is listed in the References section for your information.^4-18

PRODUCT LABELING

• DARZALEX (daratumumab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf

CLINICAL DATA

Phase 2 Study on DARZALEX Monotherapy in Stage 3B AL Amyloidosis

Kastritis et al (2024)¹ presented results from an ongoing, phase 2, open-label, multicenter, EMN 22 study that evaluated the efficacy and safety of DARZALEX monotherapy in patients with stage 3B newly diagnosed AL amyloidosis.

Study Design/Methods

• Patients with newly diagnosed stage 3B AL amyloidosis were included.
• Dosing
  • All patients initially received monotherapy with DARZALEX 16 mg/kg IV, followed by DARZALEX FASPRO 1800 mg subcutaneously (SC; since February 2020).
  • Treatment was administered on days 1, 8, 15, and 22 during cycles 1-2; on days 1 and 15 during cycles 3-6; and on day 1 during cycle 7+ until disease progression, start of a new therapy, or for a maximum of 2 years.
• Patients unable to achieve either a hematologic very good partial response (VGPR) or better or a hematologic partial response (PR) with a major organ response by cycle 4 could additionally receive bortezomib 1.3 mg/m² weekly (maximum 6 cycles) and low-dose dexamethasone at investigator’s discretion.
• Primary endpoint: OS rate at 6 months
• Key secondary endpoints: Hematologic ORR at 3 and 6 months, organ response rate, major organ deterioration progression free survival (MOD-PFS; from cycle 1 day 1 until death, clinical manifestation of cardiac/renal failure, or development of hematologic progression of progressive disease [PD] as per consensus guidelines), safety, and tolerability of DARZALEX.

Results

Patient Characteristics

• At a clinical data cutoff of December 15, 2023, 40 patients had been enrolled in the study, of whom 10 (25.0%) patients had completed the study treatment, 4 (10.0%) patients continued the treatment, and 26 patients discontinued the treatment (PD, n=7; safety event, n=3; death, n=14; consent withdrawal, n=1; physician's decision, n=1).
• The median duration of follow-up was 10.3 months (range, <0.1-50.1).
• The median duration of therapy was 6.6 months (range, <0.1-25.3).
• The median number of DARZALEX infusions was 18 (range, 1-36).
• Baseline patient and treatment characteristics are summarized in Table: Baseline Patient and Treatment Characteristics.

Efficacy

• A summary of efficacy outcomes is presented in Table: Efficacy Outcomes at Different Timepoints.

Safety

• A summary of safety outcomes is presented in Table: Summary of Safety Outcomes.
• A list of common SAEs is presented in Table: Common SAEs.
• Mortality rate at 15 days following cycle 1 day 1 of the treatment was 7.5% (deaths, n=3).
• Mortality rate at 1-month following cycle 1 day 1 of the treatment was 10.0% (deaths, n=4).

Real-world Experience of DARZALEX Monotherapy in AL Amyloidosis With Renal Involvement

Rabajoli et al (2023)² presented the results from a real-life, long-term experience that evaluated DARZALEX monotherapy in patients with AL amyloidosis.

Study Design/Methods

• Patients with AL amyloidosis, who were treated with DARZALEX alone with 24 IV administrations at a dose of 16 mg/kg, were included in the study.
• All patients had histological confirmation and staging of renal involvement before starting the treatment and were ineligible for autologous stem cell transplantation (ASCT).
• Overt multiple myeloma (MM) was excluded via bone marrow (BM) biopsy; patient could have been naïve/refractory.
• Hematological and organ response was evaluated after every 4 infusions via N-terminal prohormone of brain natriuretic peptide (NT-proBNP), difference in involved and uninvolved free light chain (dFLC) and free light chain (FLC) ratio, serum creatinine up to (24h), and serum and urine testing.
• Responses were defined based on the International Society of Amyloidosis extended criteria.
• Patients who had undergone the whole cycle of therapy underwent a second kidney biopsy at the end of the treatment based on the feasibility.

Results

Baseline Characteristics

• A total of 17 patients (mean age, 73 years) were included; of whom 16 had proteinuria (within the nephrotic range, n=11), which was associated with impairment of renal function in 11 patients.
• Two patients were on dialysis at the time of therapy initiation; 9 patients had completed the treatment; and 13 patients had received at least 12 infusions of DARZALEX.
• The mean duration of follow-up was 30 months (range, 19-46). 

Efficacy

• At the 12th DARZALEX infusion, 11 of 13 patients (84.6%) had achieved an overall hematological response, 6 patients (46.5%) had achieved a complete hematological response, 5 patients (38%) had achieved a VGPR, and 2 patients (15.5%) were non-responders.
• In regard to the renal response, 5 of 13 patients had achieved an organ response, and 6 patients did not meet the renal response criteria; the 2 patients who were on dialysis at the time of therapy initiation, remained on dialysis.
  • One patient had complete hematological and cardiac responses, the remaining patients did not have any response.
  • Seven of 9 patients had achieved a renal response.
  • 24-hour proteinuria values dropped from 6.02 g/24 hours (range, 0.8-16.8) to 1.28 g/day (range 0.9-3.6; P<0.005).
  • Stabilization or improvement of sCr increased from 1.66 mg/dL to 1.1 mg/dL (P=0.17).
  • Eight of 9 patients with cardiac involvement received at least amelioration.
• At the end of follow-up, 5 patients had persistent hematological and renal response.
• One patient with initial PR had a relapse and initiated a treatment with bortezomib + cyclophosphamide + dexamethasone.

Safety

• Two patients died due to COVID-19 infection and cardiovascular disease, respectively.
• By the end of the follow-up, the last patient was alive and was being treated with a second line of therapy, because no hematologic or organ response was achieved with DARZALEX.
• A total of 7 patients underwent a second kidney biopsy at the end of the treatment, which showed stable deposits in 6 patients, while 1 patient showed a reduction in the extension and amount of amyloid deposits.

Prospective Study on DARZALEX Monotherapy in Relapsed/Refractory Systemic AL Amyloidosis

Staron et al (2023)³ presented results from a prospective study that evaluated the rates of undetectable MRD achievement in patients treated with DARZALEX, and the rates of MRD clearance and resurgence both during and after completion of DARZALEX therapy for AL amyloidosis.

Study Design/Methods

• MRD status was assessed for patients followed at the Boston University Amyloidosis Center, who were treated with a DARZALEX-based regimen and achieved a hematologic VGPR or complete response (CR) according to the consensus criteria.
• MRD assessments were performed by multiparametric 10-color flow cytometry of BM aspirates (sensitivity level of 10^-5) and repeated at 12-month intervals during follow-up.
• Clonal progression was defined as growth in the aberrant plasma cell (PC) clone size of >1 log.

Results

• A total of 66 patients, tested for MRD between 2019 and 2023, achieved hematologic CR (n=48) and hematologic VGPR (n=18).
• MRD assessment was performed once, twice, or ≥3 times for 33, 18, and 15 patients, respectively.
  • First MRD assessment was done in 33 patients while receiving the treatment at a median of 12 cycles (range, 6-23) of treatment; later, MRD was evaluated in the remaining 33 patients after a median of 1 month (range 0-25) of therapy completion.
    • Of the 23 patients (hematologic CR, n=18; hematologic VGPR, n=5) who received DARZALEX in combination with cyclophosphamide + bortezomib + dexamethasone (CyBorD) in the frontline setting, 8 patients (35%) achieved MRD-negativity at the first evaluation.
    • Of the 43 patients (hematologic CR, n=30; hematologic VGPR, n=13) who received DARZALEX monotherapy in the relapsed/refractory setting, 20 patients (47%) achieved MRD-negativity.
  • A summary of MRD profiles in 66 patients based on the number of DARZALEX cycles received at the first MRD evaluation is presented in Table: MRD Profile of Patients Based on the Number of DARZALEX Cycles Received at the First MRD Evaluation.
• Serial MRD monitoring was performed for 33 patients.
  • Of the 10 patients who continued to receive DARZALEX between MRD assessments (group 1), 6 patients had sustained MRD-negativity, 2 patients had MRDclearance (conversion from positive to negative).
  • Of the 23 patients who underwent serial MRD assessments after completing DARZALEX (group 2), 9 patients (39%) had sustained MRD negativity, 2 patients (9%) had MRD clearance, and 2 patients (9%) had MRD resurgence (conversion from negative to positive);
  • Five of ten patients had clonal progression with persistent positivity after DARZALEX completion, of whom 3 experienced a hematologic relapse.
  • A summary of the dynamic MRD tracking at 12-month intervals during (group 1) and after completion of (group 2) is presented in Table: Dynamic MRD Tracking at the 12-month Interval in Group 1 and Group 2.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 02 July 2025. This information is intended to include clinical trial studies, prospective study and retrospective analyses, rather than being all-inclusive; therefore, case reports have been excluded.