SUMMARY

• DARZALEX for intravenous (IV) use and DARZALEX FASPRO for subcutaneous (SC) use are not approved by the regulatory agencies for the treatment of patients with immune thrombocytopenia (ITP). Janssen does not recommend the use of DARZALEX or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
• DART: a multicentre, clinical, open-label total dose-escalating phase 2 study with safety run-in evaluating the efficacy and safety of DARZALEX FASPRO in adult ITP patients who have not responded adequately or relapsed after corticosteroids and at least one second-line therapy including rituximab and/or thrombopoietin receptor agonist (TPO-RA).¹ 
  • Tsykunova et al (2022)² reported results of patients in the safety run-in of a phase 2, open-label, total dose-escalating, multicenter study with a safety run-in, to evaluate the efficacy and safety of DARZALEX FASPRO in patients with ITP (DART study).
    • All 3 patients in the safety run-in have completed treatment, with 2 patients responding at week 12, and 1 patient relapsing by week 24.
    • No grade >2 adverse events (AEs) or serious AEs were reported.
  • Tsykunova et al (2025)³ presented short-term responses from the DART study. Platelet count of ≥50x10⁹/L was attained by 2/3 patients in safety run-in, 4 (44%) in cohort 1 (95% confidence interval [CI], 13.7-78.8), and 4 (44%) in cohort 2 (95% CI, 13.7-78.8). By study week 12, out of 11 responding patients, 5 (45%) patients who were on concomitant medication treatment at the start discontinued the concomitant therapy. The most common treatment-emergent adverse events (TEAEs) were infections (38%). Grade 3 serious AEs were experienced by 2 patients, 1 patient experienced an infusion-related reaction, and 1 patient had severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection with acute renal failure. After treatment completion, numerical improvement was observed for responders in all dimensions of the 36-item short form survey version 1 (SF-36v1).
• Strüßmann et al (2024)⁴ reported a case series of 7 patients with refractory ITP treated with DARZALEX FASPRO. A total of 4 patients showed complete remission, 2 patients showed no sustained response, and 1 patient showed no response.
• Strüßmann et al (2024)⁵ reported a retrospective case series of 6 consecutive patients with ITP who received DARZALEX between 2020 and 2024; 4 patients had primary ITP, and 2 patients had secondary ITP.
  • Four patients responded to treatment, whereas 1 patient did not respond to 4 applications and withdrew from the study. One patient is still under treatment.
• Several case reports and analyses of patients with ITP who received DARZALEX or DARZALEX FASPRO are referenced below.^6-18
• Retrospective cases evaluating the use of DARZALEX or DARZALEX FASPRO for autoimmune cytopenias, refractory ITP, or warm autoimmune hemolytic anemia and refractory autoimmunity before or after allogeneic hematopoietic stem cell transplantation are referenced below.^19-21
• A study exploring high-affinity autoreactive plasma cells in patients with ITP treated with DARZALEX is referenced below.²²

CLINICAL DATA

DART (NCT04703621) study evaluated the efficacy and safety of DARZALEX FASPRO in adult ITP patients who have not responded adequately or relapsed after corticosteroids and at least one second-line therapy including rituximab and/or thrombopoietin receptor agonist (TPO-RA). Tsykunova et al (2022)² reported results of patients in the safety run-in of a phase 2, open-label, total dose-escalating, multicenter study with a safety run-in to evaluate the efficacy and safety of DARZALEX FASPRO in patients with ITP. Tsykunova et al (2025)³ presented short-term responses from the DART study.

Study Design/Methods

• Twenty-one patients will be included.²³
• Patients aged ≥18 years with primary ITP and a platelet count of ≤30x10⁹/L who failed corticosteroid therapy and at least 1 second-line therapy including rituximab and/or TPO-RA were included.²
• Patients with active bleeding, secondary ITP, or concomitant autoimmune hemolytic anemia were excluded.²³
• Three patients entering the safety run-in were required to have a platelet count of
  15-30x10⁹/L and received 4 weekly DARZALEX FASPRO injections (1800 mg each), followed by a 4-week observation period.^2,3
  • The next patient in this phase was enrolled only after the previous patient completed treatment and the observational period.
• In subsequent phases of the study:^2,23
  • Cohort 1 will include 9 patients who will receive 8 weekly DARZALEX FASPRO injections.
  • Cohort 2 will include 9 patients who will receive 8 weekly DARZALEX FASPRO injections followed by 2 injections every other week if response rate is <100% and no serious safety issues appear in cohort 1.
• Before each injection, all patients will receive standard premedication with antihistamine, corticosteroid (methylprednisolone 100 mg or equivalent before first injection and 60 mg or equivalent before subsequent injections), and paracetamol.²
• During the first 8 weeks of the study, rescue ITP medications are allowed.²³
• During the 2 weeks before inclusion, patients must remain on stable dosing of steroid or TPO-RA (eltrombopag or romiplostim), with no dose escalation allowed during the study.^2,23
• Primary endpoint: platelet count ≥50x10⁹/L in 2 measurements 12 weeks after treatment initiation for safety run-in and cohort 1 and 16 weeks for cohort 2, without rescue therapy after week 8. Safety will also be assessed.^2,23
• Secondary endpoints: duration of response and time to treatment failure.^2,23
• Exploratory endpoints: role of anti-glycoprotein IIb/IIIa (GPIIb/IIIa) and Ib antibodies, serial characterization of immunocompetent cells in blood and bone marrow, and health-related quality of life and fatigue.^2,23

Results

Efficacy

• As of February 01, 2022, all 3 patients in the safety run-in completed treatment.²
  • Two patients responded to treatment at week 12, and 1 patient relapsed by week 24.
  • Only a slight decrease in immunoglobulin (Ig) G levels was observed.
• Enrollment for cohort 1 is ongoing with 5 patients so far.²

Safety

• No grade >2 AEs or serious AEs were reported.²

Short Term Responses from the DART Study

Results

Patient and Disease Characteristics

• A total of 21 patients were enrolled between January 2021 and September 2023.³ Patient and disease characteristics are detailed in Table: Patient and Disease Characteristics.

Efficacy

• Median duration of the disease at the baseline was 60.5 months.³
• Platelet count of ≥50x10⁹/L was attained by 2/3 patients in safety run-in, 4 (44%) in cohort 1 (95% CI, 13.7-78.8), and 4 (44%) in cohort 2 (95% CI, 13.7-78.8).³
• By study week 12, out of 11 responding patients, 5 (45%) patients who were on concomitant medication treatment at the start discontinued the concomitant therapy.³

Safety

• The most common TEAEs were infections (38%).³
• Grade 3 serious AEs were reported by 2 patients.³
• One patient experienced an infusion-related reaction, and 1 patient had SARS-Cov2 infection with acute renal failure.³
• All other AEs were grade 1-2.³

Patient-Reported Outcome

• After treatment completion, numerical improvement was observed for responders in all dimensions of the SF-36v1.³

Strüßmann et al (2024)⁴ reported the largest case series with the longest patient follow-up of 7 patients with refractory ITP treated with DARZALEX FASPRO.

• DARZALEX FASPRO was administered at a dose of 1800 mg SC per injection per week.
• One patient had 4 lines of prior therapy, all others had ≥5 lines of prior therapy. The patient characteristics and outcomes are presented in Table: Patient Characteristics and Outcomes.

Strüßmann et al (2024)⁵ retrospectively evaluated a case series of 6 consecutive patients with ITP who received DARZALEX FASPRO between 2020 and 2024.

• Of these 6 patients, 4 patients had primary ITP and 2 patients had secondary ITP.
  • One patient with mantle cell lymphoma and 1 patient with hairy cell leukemia, both were in complete remission of the hematological disease with persistent, refractory ITP.
• The median age of the patients was 61 (range, 32-87) years.
• One patient had 4 prior lines of therapy (LOT), with the other 5 patients receiving ≥5 LOT. All patients had rituximab exposure.
• DARZALEX FASPRO was administered at a dose of 1800 mg SC, and the application varied between 4 to 12 times.
• Four patients responded to treatment, whereas 1 patient did not respond to 4 administrations and withdrew from the study.
  • Of the 4 patients who responded, time to response (platelet count >50.000/μl) was 1, 3, 4 and 10 weeks after treatment onset.
• One patient is still under treatment.
• The duration of responses are 36, 19, 18 and 9 months. All responses are ongoing with no further treatment.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 25 June 2025.