SUMMARY

• Janssen does not recommend the use of DARZALEX for intravenous (IV) use or DARZALEX FASPRO for subcutaneous (SC) use in a manner that is inconsistent with the approved labeling.
• Among the 9 studies of DARZALEX for IV use summarized below, outpatient administrations of DARZALEX were permitted in 8 studies (GEN501,¹ EQUULEUS,^2,3 SIRIUS,⁴ GRIFFIN,^5-7 POLLUX,⁸ CASTOR,^9,10 CASSIOPEIA,^11,12 ALCYONE,¹³ and MAIA^14,15) per their clinical trial protocols. DARZALEX administration was permitted in either outpatient or inpatient settings per the clinical trial protocol for MMY3010.¹⁶
  • GEN501 was an open-label, multicenter, dose-escalating (Part 1) and dose-expansion (Part 2) phase 1/2 study assessing the safety of DARZALEX monotherapy in patients with multiple myeloma (MM) who had relapsed after or were refractory to ≥2 prior lines of therapy, including proteasome inhibitors (PIs), immunomodulatory agents, chemotherapy, and autologous stem-cell transplantation (ASCT) (N=72).¹
    • All infusions during part 2 of the study are performed as outpatient visits.¹⁷
  • EQUULEUS (MMY1001) is a phase 1b, open-label, non-randomized, multicenter study evaluating the safety, tolerability, and dose regimen of DARZALEX in combination with various backbone treatment regimens (which included pomalidomide and low-dose dexamethasone) in patients with MM that was either newly diagnosed or treated with ≥2 prior therapies.^2,3
    • Following DARZALEX administration, all study subjects were to be observed at the start and end of the infusion. If a subject experienced a significant medical event, the investigator assessed whether the subject required an overnight stay for observation.¹⁸
  • SIRIUS (MMY2002) was an open-label, multicenter, international, phase 2 study evaluating the efficacy and safety of DARZALEX monotherapy in patients with MM who have received ≥3 prior lines of therapy, including a PI and an immunomodulatory agent, or have disease refractory to both a PI and an immunomodulatory agent (N=106).⁴
    • All infusions are to be performed as outpatient visits.¹⁹
  • GRIFFIN (MMY2004) was a 2-part, open-label, multicenter, phase 2, randomized, active-controlled study in United States evaluating the safety and efficacy of DARZALEX in combination with bortezomib, lenalidomide, and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose therapy and ASCT.^5-7
    • All infusions were planned as outpatient visits.²⁰
  • POLLUX (MMY3003) is a randomized, open-label, multicenter, phase 3 study evaluating the safety and efficacy of lenalidomide and dexamethasone (Rd) and DARZALEX + Rd in patients with relapsed or refractory multiple myeloma (RRMM).⁸
    • All infusions may be performed as outpatient visits.²¹
  • CASTOR (MMY3004) is a multicenter, randomized, open-label, active controlled, phase 3 study that evaluated the safety and efficacy of bortezomib and dexamethasone (Vd) alone and DARZALEX + Vd in patients with RRMM.^9,10
    • All infusions were planned as outpatient visits.²²
  • CASSIOPEIA (MMY3006) is an ongoing open-label, randomized, multicenter, active-controlled study evaluating the safety and efficacy of treatment with bortezomib, thalidomide, and dexamethasone (VTd) alone and DARZALEX + VTd in patients with NDMM eligible for ASCT.^11,12
    • In MMY3006, all infusions were planned as outpatient visits.²³
  • ALCYONE (MMY3007) is an ongoing, open-label, active controlled, multicenter, randomized, phase 3 study evaluating the safety and efficacy of bortezomib, melphalan, and prednisone (VMP) alone and DARZALEX + VMP in patients with NDMM who were ineligible for high-dose chemotherapy with ASCT.¹³
    • Following DARZALEX administration, all study subjects were to be observed at the start and end of the infusion. If a subject experienced a significant medical event, the investigator assessed whether the subject required an overnight stay for observation.²⁴
  • MAIA (MMY3008) is an ongoing, international, phase 3, randomized, open-label, active-controlled, multicenter study evaluating the safety and efficacy of DARZALEX in combination with Rd compared to Rd in transplant-ineligible patients with NDMM (N=737).^14,15
    • All infusions were planned as outpatient visits.²⁵
  • MMY3010 is an open-label treatment use protocol for DARZALEX in patients with MM who have received ≥3 prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent, who reside in areas where DARZALEX is not yet commercially available through local healthcare providers, who have not been enrolled in another daratumumab study, and who are not eligible for enrollment in or do not have access to another ongoing clinical study of daratumumab (anticipated maximum N=2000).¹⁶
    • In MMY3010, infusions may be performed as outpatient or inpatient visits, depending on local clinical practice.¹⁶
• Among the 4 studies of DARZALEX FASPRO for SC use summarized below, all doses of DARZALEX FASPRO were to be administered at outpatient visits in all studies (COLUMBA,²⁶ APOLLO,²⁷ ANDROMEDA,²⁸ and PLEIADES^29-33) per their clinical trial protocols.
  • COLUMBA (MMY3012) is an ongoing phase 3, randomized, open-label, multicenter, non-inferiority study evaluating the efficacy, pharmacokinetics, and safety of DARZALEX vs DARZALEX FASPRO in patients with RRMM.²⁶
    • All doses of DARZALEX or DARZALEX FASPRO were to be administered at outpatient visits.³⁴
  • APOLLO (MMY3013) is an ongoing, phase 3, randomized, open-label, multicenter study evaluating the safety and efficacy of DARZALEX FASPRO in combination with pomalidomide and dexamethasone (DPd) vs Pd in patients with RRMM who received ≥1 prior treatment with both lenalidomide and a PI.²⁷
    • All subjects were to be observed for at least 6 hours after the end of the DARZALEX FASPRO SC injection during cycle 1 day 1 and, if deemed necessary, after consecutive injections.³⁵
  • ANDROMEDA (AMY3001) is an ongoing, prospective, randomized, active-controlled, multicenter, phase 3 study evaluating the efficacy and safety of DARZALEX FASPRO in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd) compared to VCd alone in newly diagnosed patients with systemic immunoglobulin light-chain amyloidosis.²⁸
    • All doses of DARZALEX FASPRO were planned as outpatient visits.³⁶
  • PLEIADES (MMY2040) is an ongoing, non-randomized, open-label, multicenter, phase 2 study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with various treatment regimens in patients with MM.^29-33
    • Following DARZALEX FASPRO administration, all study subjects were to be observed for at least 6 hours during day 1 of cycle 1 and, if deemed necessary by the investigator, after consecutive injections. If a subject experienced a significant medical event, the investigator assessed whether the subject required an overnight stay for observation.³⁷
• The following is a detailed summary of key data presented during recent conference:
  • Binder et al (2024)³⁸ presented (at the 66^th ASH Annual Meeting) results from an open-label, single-arm study that assessed implementation of home-based administration of DARZALEX FASPRO for patients with MM. No significant difference was identified in the primary outcome (Satisfaction with Therapy [SWT] score) and secondary outcome (quality of life [QoL]) when comparing HC with treatment at the infusion center. No unique AEs related to home administration and no unexpected AEs related to medications were reported.
  • Lund et al (2024)³⁹ presented results from a study that assessed administration of DARZALEX outside the hospital as well as the effectiveness of electronic patient-reported outcome (PRO) data for pretreatment evaluation of whether patients needed to talk to a healthcare practitioner before each injection.
    • Of the of 269 planned DARZALEX administrations, 125 were hospital-planned administrations and 144 were planned to be given outside the hospital.³⁹
    • On average, patients saved 177 minutes per administration given at home (29 minutes) vs the hospital (206 minutes).³⁹
  • De Angelis et al (2023)⁴⁰ presented (at the 65^th American Society of Hematology [ASH] Annual Meeting) results of DARZALEX FASPRO administered at home to frail patients with MM. Among 12 patients who were evaluable for response, 1 achieved stringent complete remission (sCR) and 4 achieved very good partial remission (VGPR), yielding an overall response rate (ORR) of 42%; furthermore, 5 patients had stable disease (SD), and 2 patients had progressive disease (PD). The main adverse events (AEs) that occurred during domiciliary treatment included infections (pneumonia [n=4], sepsis [n=2], cystitis [n=1]), and deep vein thrombosis (n=1). In the long-term residential accommodation (LTRA) group, 80% of patients (4/5) experienced infections, which were fatal in 3 cases. Conversely, in the home care (HC) group, 30% of patients (3/10) experienced infections, with only 1 resulting in death. At the last follow-up, 8 patients were alive (2 were awaiting a transplant procedure) and 7 patients were reported to have died (PD, n=3; infective complications, n=3; and heart disease, n=1).

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

Binder et al (2024)³⁸ presented results from an open-label, single-arm study (from December 9, 2022, to April 17, 2024) that assessed implementation of home-based administration of DARZALEX FASPRO for patients with MM.

Methods

• Overall, 20 patients (mean age, 66 years [range, 49-89]) who were receiving DARZALEX FASPRO monthly as either monotherapy or in combination with oral agents for MM were included in the study.³⁸
  • Ten patients (50%) were female, and 10 patients (50%) identified as Black or African American.
  • One patient withdrew from the trial after cycle 2, and 1 patient came off the trial for cycle 8 after significant treatment delays due to infectious complications.
  • Nineteen patients completed the home infusion portion of the study.
• Patients received 8 cycles of DARZALEX FASPRO (2 cycles at the infusion center, followed by 4 cycles at home and 2 cycles again at the infusion center).³⁸
• Primary endpoint: patients’ treatment satisfaction, assessed using the SWT domain of the Cancer Therapy Satisfaction Questionnaire (CTSQ), when receiving HC vs standard-of-care treatment at the infusion center.³⁸
• Secondary endpoints: adherence to home therapy, safety of home administration, barriers to home administration, QoL (EORTC QLG Core Questionnaire [EORTC QLQ-C30]), financial burden (COST survey), and other CTSQ domains.³⁸
  • Surveys were completed at each monthly visit, and semistructured qualitative interviews were conducted at the end of the study.

Results

• No significant difference in the primary outcome (SWT score) was identified when comparing HC vs treatment at the infusion center (mean difference, 0.7 in favor of treatment at the infusion center; 95% confidence interval, -3.02 to 1.62; P=0.551).³⁸
  • Treatment adherence at home was 100%, with minimal delays in therapy (1/76 [1.4%]).
  • No barriers to home administration were identified.
  • There were no unique AEs related to home administration and no unexpected AEs related to medications.
• No significant differences in the secondary outcomes were identified when comparing HC vs treatment at the infusion center.³⁸
  • The EORTC QLQ-C30 mean difference between HC and treatment at the infusion center was 2.08 (P=0.405).
  • Regardless of the treatment site, females experienced a significantly higher financial toxicity vs males (COST score, 7.37 points; P=0.026).
  • There was no noticeable impact of home administration on COST score (0.18 points; P=0.812).

Lund et al (2024)³⁹ presented results from a study that assessed administration of DARZALEX outside the hospital (by a district nurse at home or in a local healthcare clinic) as well as the effectiveness of electronic PRO data for pretreatment evaluation of whether patients needed to talk to a healthcare practitioner before each injection.

• Of the 269 planned DARZALEX administrations, 125 were hospital-planned administrations and 144 were planned to be given outside the hospital.³⁹
  • Of the 125 hospital-planned administrations, 122 (97.6%) were given and 1 was cancelled.
  • Of the 144 outsource administrations, 133 (92.4%) were given as planned, 6 were redirected and given at the hospital (2 due to suspicion of infection and 4 for administrative reasons), and 5 were cancelled.
• On average, patients saved 177 minutes per administration given at home (29 minutes) vs the hospital (206 minutes).³⁹
  • For patients treated at home, time was reduced by a factor of 3.25 (home vs local healthcare clinic: 63 minutes vs 205 minutes, respectively).
• The number of unplanned health contacts did not differ significantly between home and hospital administrations.³⁹
• Overall, 84% of patients preferred to continue with home treatment.³⁹
• The PRO questionaries had a positive predictive value of 100%.³⁹
  • Prior to each treatment, patients reported their side effects electronically and an algorithm was developed to stratify patients as ready or not for planned treatment.
  • In 171 of 223 cases, the algorithm recommended treatment; in 52 cases, it recommended medical evaluation.
  • Among these 52 cases, 44 received planned treatment and 8 were cancelled/postponed.
• Only 40% of patients preferred to receive calls from the nurse prior to each treatment afterward; furthermore, 52% of patients preferred to continue reporting side effects via the application.³⁹

De Angelis et al (2023)⁴⁰ presented (at the 65^th ASH Annual Meeting) results of a study of DARZALEX/DARZALEX FASPRO administered to frail patients with MM in an outpatient setting.

Results

Baseline Patient Characteristics

• Per the MyelHome project, 15 patients with MM were treated as outpatients. Of these, 10 received HC and 5 received care in LTRA.⁴⁰
• Patients received 2 initial doses of either DARZALEX or DARZALEX FASPRO at a hospital to mitigate side effects and received subsequent doses as outpatients. The first outpatient dose was administered by both a nurse and a physician, whereas subsequent doses were administered by nurses only.⁴⁰
• Overall, 110 administrations of DARZALEX FASPRO were performed by Domiciliary Hematologic Care Unit nurses in an outpatient setting.⁴⁰
• Baseline patient characteristics are summarized in Table: Baseline Characteristics (Myelhome Project).

Efficacy

• Among 12 patients who were evaluable for response, 1 achieved sCR and 4 achieved VGPR (ORR, 42%); furthermore, 5 and 2 patients had SD and PD, respectively.⁴⁰

Safety

• During and/or immediately following home administration, 1 patient experienced a grade 2 allergic reaction (per World Health Organization classification); thus, DARZALEX FASPRO was permanently discontinued after the second dose was administered.⁴⁰
• The main AEs that occurred during domiciliary treatment included infections (pneumonia [n=4], sepsis [n=2], cystitis [n=1]), and deep vein thrombosis (n=1).⁴⁰
• In the LTRA group, 80% of patients (4/5) experienced infections, which were fatal in 3 cases. Conversely, in the HC group, 30% of patients (3/10) experienced infections, with only 1 resulting in death.⁴⁰
• At the last follow-up, 8 patients were alive (2 of whom were awaiting a transplant procedure) and 7 patients were reported to have died (PD, n=3; infective complications, n=3; and heart disease, n=1).⁴⁰

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 13 January 2025 pertaining to this topic.