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DARZALEX® SC studies

Efficacy and safety of DARZALEX® SC in multiple myeloma: Clinical overview of PAVO, COLUMBA and PLEIADES studies

In this interactive video, Prof. Mateos gives an overview of the DARZALEX® SC PAVO, COLUMBA and PLEIADES studies. Use the video’s navigation tool to access topics of interest, including study designs, efficacy, safety, and a Q&A with Prof. Mateos, where she provides her expert opinion on the integration of DARZALEX® SC into clinical practice based on her experience from clinical trials.

Related content

DARZALEX® SC home

DARZALEX® SC handling and administration

Handling and administration demonstration & information

DARZALEX® SC support materials

A range of materials, including a practical guide, in-clinic poster and patient materials

DARZALEX® SC MOA

See how the recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE® drug delivery technology) added to DARZALEX® facilitates the subcutaneous administration of the drug

PAVO

PAVO dose-finding study

DARZALEX® SC 1,800 mg has an acceptable pharmacokinetic profile with similar response rates to DARZALEX® IV[1]

PAVO is a phase 1b, open-label, multicentre, dose-finding, proof-of-concept study in RRMM patients with ≥2 prior lines of treatment who have not received anti-CD38 therapy.[1]

In Part 1 of the study, patients received 28-day cycles of daratumumab 1,200 mg + rHuPH20 30,000 U (in 60 mL; Group 1) or daratumumab 1,800 mg + rHuPH20 45,000 U (in 90 mL; Group 2) following the approved IV monotherapy dosing schedule (QW in Cycles 1 and 2, Q2W in Cycles 3 through 6, and Q4W thereafter).[1]

In Part 2 of the study, patients received a concentrated co-formulation of the selected daratumumab (1,800 mg) and rHuPH20 (30,000 U in 15 mL) dose in a single, pre-mixed vial.[1]

PAVO proof-of-concept data
Slower systemic absorption with SC vs. IV[1]
Maximum Ctrough is similar or higher following 1,800 mg SC compared with 16 mg/kg IV[1]
Cmax at Q4W dosing – 1,800 mg SC is similar to 16 mg/kg IV overall[1]
Clinical response rates similar to IV[1]
PAVO safety data

DARZALEX® SC was well tolerated with an AE profile consistent with DARZALEX® IV[1]

  • Grade 3/4 TEAEs occurred in 40% of patients
  • No serious drug-related TEAEs
  • No TEAE-related treatment discontinuations
  • IRRs occurred in 12% of patients (all within 6 hours of the first injection); IV IRRs = 45–56%[2][3][4][5][6][7]
  • No Grade 4 IRRs were reported
  • No discontinuations due to IRRs
  • No delayed occurrences of IRRs

COLUMBA

COLUMBA non-inferiority study

DARZALEX® SC flat dose 1,800 mg is non-inferior to DARZALEX® IV[8]

COLUMBA is a phase 3, randomised, open-label, active-controlled, multicentre non-inferiority study of DARZALEX® SC versus DARZALEX® IV in patients with heavily pre-treated RRMM. N=522*[8]

* After at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.

COLUMBA efficacy and patient-reported outcomes

NEW DATA COLUMBA: Primary and final analysis of Part 1 of the study[8]

Overall response rate*

Progression-free survival at 12 months

Overall survival at 12 months

*DARZALEX® SC vs. DARZALEX® IV at median follow-up of 13.7 months.[9]

Subgroup analyses
No dose individualisation of DARZALEX® SC based on body weight is necessary:[10][11]
  • ORRs in the DARZALEX® SC and DARZALEX® IV body weight subgroups of ≤65 kg, >65–85 kg and >85 kg were consistent with the ITT population[10]
  • The higher concentration of DARZALEX® SC in patients ≤65 kg did not have a clinically relevant effect on safety[10]
  • In some patients with body weight >120 kg, lower exposure was observed, which may result in reduced efficacy. However, this observation is based on a limited number of patients[11]
  • No dose adjustment based on body weight is currently recommended[11]
Patient-reported outcomes
DARZALEX® SC patients were more satisfied with their cancer therapy than IV patients[9]
Modified Cancer Treatment Satisfaction Questionnaire[9]
  • Patient-reported satisfaction with therapy was measured using a modified version of the Cancer Therapy Satisfaction Questionnaire (CTSQ) that included 9 items specific to satisfaction with therapy, and a domain score was calculated based on 7 of 9 items
COLUMBA safety data

DARZALEX® SC offers a similar safety profile with fewer and less severe IRRs vs. DARZALEX® IV[8]

Grade >3 TEAEs:[8]

TEAEs leading to discontinuation:[8]

IRRs:[8]

Grade 3 IRRs:[8]

Injection-site reactions (ISRs) occurred in 7% of DARZALEX® SC patients (all Grade 1/2)[8]

PLEIADES

PLEIADES combination treatment study

DARZALEX® SC 1,800 mg flat dose in combination with standard treatment regimens is comparable to DARZALEX® IV clinical studies[12][13]

PLEIADES is a phase 2, multicentre, open-label study of DARZALEX® SC in combination with standard of care. N=199[12]

Study arms included:[12]

  • DARZALEX® + VMP: NDMM and ineligible for high-dose chemotherapy and ASCT due to age (≥65 years) or the presence of comorbid conditions that would make ASCT intolerable
  • DARZALEX® + Rd: RRMM with ≥1 prior line of therapy and evidence of response (partial response or better) to ≥1 prior line of therapy
PLEIADES efficacy data

DVMP: ORR in transplant-ineligible NDMM[13][14]

DRd: ORR in RRMM with ≥1 prior line of therapy[13][15]

MRD-negativity (10-5)[13]

MRD-negativity rates in DARZALEX® IV trials[14][15]

PLEIADES safety data

DARZALEX® SC offers a similar safety profile with a lower rate of IRRs vs. DARZALEX® IV[13]

  • DARZALEX® SC combination therapies were well tolerated, and no new safety concerns were identified
  • Grade 3/4 TEAEs occurred in 78% of patients in the DVMP cohort and 94% of patients in the DRd cohort
  • The most common Grade 3/4 TEAE was neutropenia (DVMP=37%; DRd=55%)
  • IRRs occurred in only 9% and 5% of patients in the DVMP and DRd cohorts, respectively
  • In both the DVMP and DRd cohorts, IRRs were mild (grade 1/2); no patients experienced a grade 4 IRR
  • ISRs occurred in 6% of patients in both DVMP and DRd cohorts (all grade 1/2)

Quick downloads

SC Checklist beginning of treatment

Includes a first use checklist of Darzalex® SC.

Darzalex® SC Practical Guide

Includes DARZALEX® SC handling and administration info, pre and post-injection medications, and more

Glossary

AE: adverse event 

ASCT: autologous stem cell transplant 

ASH: American Society of Hematology 

C3D1: Cycle 3 Day 1 

CI: confidence interval 

Cmax: maximum concentration 

Ctrough: trough concentration 

DRd: DARZALEX®, lenalidomide, dexamethasone 

DVMP: DARZALEX®, Velcade®, melphalan, prednisone 

IRR: infusion-related reaction

ISR: injection-site reaction 

ITT: intention to treat 

IV: intravenous 

MOA: mode of action 

MRD: minimal residual disease 

NDMM: newly-diagnosed multiple myeloma 

ORR: overall response rate 

PO: oral 

QW: every week

Q2W: every 2 weeks 

Q4W: every 4 weeks 

Rd: lenalidomide, dexamethasone 

rHuPH20: recombinant human hyaluronidase 

RRMM: relapsed/refractory multiple myeloma

PH20 RRMM: relapsed/refractory multiple myeloma 

SC: subcutaneous 

TEAE: treatment-emergent adverse event 

VMP: Velcade®, melphalan, dexamethasone

Para visualizar o IECRCM de Darzalex, veja aqui.

Referências

Chari A, et al. Subcutaneous Delivery of Daratumumab in Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM): Pavo, an Open-Label, Multicenter, Dose Escalation Phase 1b Study. Oral presentation at the 59th American Society of Hematology annual meeting; December 9–12, 2017; Atlanta, GA. Abstract 838.
Usmani SZ, et al. Subcutaneous delivey of daratumumab in relapsed or refractory multiple myeloma. Blood. 2019;134(8)668-677.
Plesner T et al. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood. 2016;128(14):1821–1828.
Chari A et al. Results of an early access treatment protocol of daratumumab in United States patients with relapsed or refractory multiple myeloma. Cancer. 2018;124(22):4342–4349.
Palumbo A et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754–766.
Dimopoulos MA et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319–1331.
Chari A, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017; 130(8): 974-981.
Mateos MV, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020;7(5):e370–e380.
Usmani SZ, et al. Randomized, Open-label, Non-inferiority, Phase 3 Study of Subcutaneous (SC) Versus Intravenous (IV) Daratumumab (DARA) Administration in Patients With Relapsed or Refractory Multiple Myeloma: COLUMBA Update. Poster presented at the 61st American Society of Hematology annual meeting; December 7–10, 2019; Orlando, FL. Poster 1865.
Mateos MV, et al. Randomized, Open-label, Non-inferiority, Phase 3 Study of Subcutaneous (SC) Versus Intravenous (IV) Daratumumab (DARA) Administration in Patients (Pts) With Relapsed or Refractory Multiple Myeloma (RRMM): Body Weight Subgroup Analysis of COLUMBA. Poster presented at the 61st American Society of Hematology annual meeting; December 7–10, 2019; Orlando, FL. Poster 1906.
RCM DARZALEX ®. Acedido em março de 2022. Disponível em www.ema.europa.eu
Chari A, et al. Subcutaneous Daratumumab Plus Standard Treatment Regimens in Patients WithMultiple Myeloma Across Lines of Therapy: PLEIADES Study Update. Poster presented at the 61st American Society of Hematology annual meeting; December 7–10, 2019; Orlando, FL. Poster 3152.
Moreau P, et al. Subcutaneous Daratumumab (DARA SC) Plus Standard-of-Care (SoC) Regimens in Multiple Myeloma (MM) across Lines of Therapy in the Phase 2 Pleiades Study: Initial Results of the Dara SC Plus Carfilzomib/Dexamethasone (D-Kd) Cohort, and Updated Results for the Dara SC Plus Bortezomib/Melphalan/Prednisone (D-VMP) and Dara SC Plus Lenalidomide/Dexamethasone (D-Rd) Cohorts. Poster presented at the American Society of Hematology (ASH) annual meeting & exposition. Virtual meeting. December 5–8, 2020. #1380.
Mateos MV, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated Myeloma. N Engl J Med. 2018; 378(6): 518-528.
Kaufman JL, et al. Four-Year Follow-up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM). Poster presented at the 61st annual meeting of the American Society of Hematology (ASH) annual meeting & exposition. Orlando, FL. December 7–10, 2019. #1866.
CP-287862 - Março 2022