Would you consider frontline DARZALEX FASPRO® + VRd for a transplant-eligible patient like Philip?
Hypothetical patient
Philip is a transplant-eligible patient with a moderately active lifestyle
Age:
62 years old
Job:
Information systems manager
Biography:
- Married; with 2 adult children
- Enjoys going on long walks with his spouse and pet dog
- Actively manages his health and treatment plan
Newly diagnosed and eligible for a transplant
Transplant eligibility of an individual patient is determined based on evaluation by the treating physician.
Clinical condition and disease presentation
- ISS disease stage: I
- ECOG PS: 1
- Cytogenetic risk: Standard*
Additional considerations
- Mild anemia (9 g/dL)
- Shortness of breath
Presents with:
Discover PERSEUS trial results relevant for treating patients like Philip
DVRd=DARZALEX FASPRO® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); del=deletion; ECOG PS=Eastern Cooperative Oncology Group Performance Status; ISS=International Staging System; t=translocation; VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*Cytogenetic risk was based on fluorescence in situ hybridization (FISH); high cytogenetic risk was defined as the presence of one of the following abnormalities: del(17p), t(4;14), or t(14;16).1,2
THE PERSEUS TRIAL: DARZALEX FASPRO® + VRd
Approval for the treatment of transplant-eligible patients with newly diagnosed multiple myeloma was based on the results of a phase 3 randomized, multicenter, open-label trial1,2
¶The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® + R for maintenance has not been established.1
Primary endpoint was progression-free survival (PFS) based on International Myeloma Working Group (IMWG) criteria.1
Key secondary endpoints included overall response rate (ORR), minimal residual disease (MRD) negativity rate (next-generation sequencing [NGS];10-5).1,2#
Is your patient a potential fit for DARZALEX FASPRO® + VRd?
ASCT=autologous stem cell transplant; CR=complete response; d=dexamethasone (d); D=DARZALEX FASPRO® (D); DR=DARZALEX FASPRO® (D) + lenalidomide (R); DVRd=DARZALEX FASPRO® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); ECOG PS=Eastern Cooperative Oncology Group Performance Status; ISS=International Staging System; IV=intravenous; NDMM=newly diagnosed multiple myeloma; NGS=next-generation sequencing; PO=by mouth; QW=weekly; Q2W=every 2 weeks; R=lenalidomide (R); SC=subcutaneous; V=bortezomib (V); VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*Within 12 weeks of ASCT, and when engraftment was complete.1
†Stratified by ISS stage and cytogenetic risk.2
‡DARZALEX FASPRO® 1,800 mg co-formulated with rHuPH20 (2,000 U/mL).1
§On the days of DARZALEX FASPRO® injection, the dexamethasone dose was administered orally or intravenously as a pre-injection medication.1
‖After Week 16, patients underwent stem cell mobilization, high-dose chemotherapy, and ASCT.1
#MRD negativity rate was defined as the proportion of patients who achieved both MRD negativity and ≥CR. MRD was assessed using a next-generation sequencing assay (clonoSEQ).1
In the treatment of transplant-eligible patients with newly diagnosed multiple myeloma1:
Baseline demographics and disease characteristics were similar between the 2 treatment groups2,3
| Patient Characteristics | DARZALEX FASPRO® + VRd (n=355) | VRd (n=354) |
|---|---|---|
| Median age (y) | 61 | 59 |
| Age category (%) | ||
| <50 yrs | 15 | 15 |
| ≥50 and <65 yrs | 58 | 60 |
| ≥65 yrs | 27 | 25 |
| ECOG PS* (%) | ||
| 0 | 62 | 65 |
| 1 | 32 | 31 |
| 2 | 5 | 5 |
| 3 | 0 | 0 |
| ISS disease stage† (%) | ||
| I | 52 | 50 |
| II | 32 | 35 |
| III | 15 | 14 |
| Cytogenetic profile (%) | ||
| Standard risk | 74 | 75 |
| High risk‡ | 21 | 22 |
| Indeterminate | 4 | 3 |
| Revised standard risk | 49 | 47 |
| Revised high risk§ | 37 | 42 |
| Indeterminate | 14 | 11 |
The PERSEUS trial included patients of various ages, performance status, and cytogenetic abnormalities2
amp=amplification; CI=confidence interval; del=deletion; DVRd=DARZALEX FASPRO® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); ECOG PS=Eastern Cooperative Oncology Group Performance Status; ISS=International Staging System; t=translocation; VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*ECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.2
†ISS disease stage was based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.2
‡Cytogenetic risk was based on fluorescence in situ hybridization (FISH); high cytogenetic risk was defined as the presence of one of the following abnormalities: del(17p), t(4;14), or t(14;16).1,2
§Revised cytogenetic risk was defined as the presence of del(17p), t(4;14), t(14;16), gain(1q21), or amp(1q21).4
In the treatment of transplant-eligible patients with newly diagnosed multiple myeloma1:
Frontline DARZALEX FASPRO® + VRd significantly reduced the risk of progression or death in patients vs VRd alone after a median follow-up of 47.5 months1,2*
The median time to reach post-transplant consolidation was 9.9 months in the DVRd arm
(range: 0.5-18.5 months).1
(range: 0.5-18.5 months).1
reduction in the risk of disease progression or death with DARZALEX FASPRO® + VRd
vs VRd alone (HR=0.40; 95% CI: 0.29-0.57; P<0.0001)1,2*‡
vs VRd alone (HR=0.40; 95% CI: 0.29-0.57; P<0.0001)1,2*‡
These results are based on the full treatment regimen and include investigational maintenance of DARZALEX FASPRO® + R following post-transplant consolidation. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® + R for maintenance has not been established.1
CI=confidence interval; DR=DARZALEX FASPRO® (D) + lenalidomide (R); DVRd=DARZALEX FASPRO® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; IMWG=International Myeloma Working Group; IRC=Independent Review Committee; mPFS=median progression-free survival; PFS=progression-free survival; R=lenalidomide (R); VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*Median follow-up was 47.5 months in the DVRd and VRd group (range: 0.0-54.4 months).2
†Kaplan-Meier estimate.5
‡Progression-free survival was by IRC assessment based on IMWG criteria.1
PFS rates in patients with high cytogenetic risk based on the revised definition4*
High cytogenetic risk is defined as having at least 1 out of the following 5 abnormalities: del(17p), t(4;14), t(14;16), gain(1q21), or amp(1q21)4
risk reduction for disease progression or death with DARZALEX FASPRO® + VRd vs VRd alone (HR=0.53; 95% CI: 0.35, 0.81)4*
In a subgroup analysis of patients with cytogenetic risk based on the protocol definition: 41% risk reduction for disease progression or death with DARZALEX FASPRO® + VRd vs VRd alone (HR=0.59; 95% CI: 0.39, 0.99)4*
This analysis was conducted post hoc and no conclusions should be drawn.
These results are based on the full treatment regimen and include investigational maintenance of DARZALEX FASPRO® + R following post-transplant consolidation. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase. The efficacy of DARZALEX FASPRO® + R for maintenance has not been established.1
PFS rates in patients based on chromosome 1q21 status4*
risk reduction for disease progression or death with DARZALEX FASPRO® + VRd vs VRd alone (HR=0.52; 95% CI: 0.31, 0.88)4*
amp=amplification; CI=confidence interval; del=deletion; DVRd=DARZALEX® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; NR=not reached; PFS=progression-free survival; t=translocation; VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*Median follow-up was 47.5 months.4
This analysis was conducted post hoc and no conclusions should be drawn.
These results are based on the full treatment regimen and include investigational maintenance of DARZALEX FASPRO® + R following post-transplant consolidation. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase. The efficacy of DARZALEX FASPRO® + R for maintenance has not been established.1
In the treatment of transplant-eligible patients with newly diagnosed multiple myeloma1:
Overall response rates through post-transplant consolidation for frontline DARZALEX FASPRO® + VRd vs VRd alone1*
The median time to reach post-transplant consolidation was 9.9 months in the DVRd arm (range: 0.5-18.5 months)1
44.5% of patients achieved ≥CR with DVRd, vs 34.7% with VRd alone1
CR=complete response; DVRd=DARZALEX FASPRO® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; ORR=overall response rate; PR=partial response; sCR=stringent complete response; VGPR=very good partial response; VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*Based on intent-to-treat population.1
In the treatment of transplant-eligible patients with newly diagnosed multiple myeloma1:
MRD negativity rates through post-transplant consolidation at 10-5 threshold for frontline DARZALEX FASPRO® + VRd vs VRd alone1*
CR=complete response; DVRd=DARZALEX FASPRO® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); MRD=minimal residual disease; VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*MRD negativity rate was defined as the proportion of patients who achieved both MRD negativity and ≥CR. MRD was assessed using a next-generation sequencing assay (clonoSEQ).1
†Based on intent-to-treat population who achieved MRD negativity (10-5) through post-transplant consolidation and ≥CR at any time during the study.1
‡Patients who achieved MRD negativity (threshold of 10-5) and ≥CR through post-transplant consolidation.1
In the treatment of transplant-eligible patients with newly diagnosed multiple myeloma1:
Demonstrated safety profile through post-transplant consolidation for frontline DARZALEX FASPRO® + VRd1
Adverse reactions reported in ≥10% of patients who received DVRd through post-transplant consolidation1
| DVRd (n=351) | VRd (n=347) | |||
|---|---|---|---|---|
| Adverse reaction | All grades (%) | Grades 3 or 4 (%) | All grades (%) | Grades 3 or 4 (%) |
| Peripheral neuropathy* | 52 | 5 | 54 | 4 |
| Paraesthesia | 11 | <1¶ | 11 | <1¶ |
| Fatigue† | 35 | 3¶ | 37 | 5¶ |
| Edema† | 22 | 1 | 21 | 1¶ |
| Pyrexia | 21 | 2¶ | 22 | 3¶ |
| Upper respiratory tract infection‡ | 32 | 1¶ | 26 | 2¶ |
| Pneumonia§ | 14 | 9 | 10 | 6# |
| Constipation | 31 | 2¶ | 30 | 2¶ |
| Diarrhea | 23 | 3¶ | 25 | 5¶ |
| Nausea | 16 | 1¶ | 12 | 1¶ |
| Abdominal pain† | 11 | 0 | 12 | 0 |
| Musculoskeletal pain† | 26 | 1¶ | 23 | 1¶ |
| Muscle spasm | 12 | 0 | 9 | <1¶ |
| Insomnia | 26 | 2¶ | 12 | 2¶ |
| Rash† | 25 | 3¶ | 31 | 5 |
| Hepatotoxicity‖ | 16 | 6¶ | 16 | 5 |
| Cough† | 12 | <1¶ | 8 | 0 |
The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash1
Select laboratory abnormalities (≥30%) that worsened from baseline in patients who received DVRd through post-transplant consolidation1
| DVRd (n=351)** | VRd (n=346)** | |||
|---|---|---|---|---|
| Laboratory abnormality | All grades (%) | Grades 3 or 4 (%) | All grades (%) | Grades 3 or 4 (%) |
| Hematology | ||||
| Decreased platelets | 89 | 34 | 78 | 25 |
| Decreased lymphocytes | 87 | 69 | 69 | 43 |
| Decreased leukocytes | 78 | 47 | 56 | 22 |
| Decreased neutrophils | 67 | 52 | 47 | 34 |
| Decreased hemoglobin | 39 | 7 | 43 | 6 |
| Chemistry | ||||
| Increased alanine aminotransferase (ALT) | 52 | 7 | 48 | 5 |
| Decreased sodium | 40 | 5 | 25 | 5 |
| Increased alkaline phosphatase | 39 | 0 | 36 | 1 |
| Decreased potassium | 30 | 6 | 24 | 3 |
In patients who received DVRd1:
- 37% experienced serious adverse reactions
- >5% experienced most frequent serious adverse reactions: pneumonia (6%)
- 1.7% experienced fatal adverse reactions#
- 2% experienced permanent treatment discontinuation due to an adverse reaction
- An adverse reaction which resulted in permanent discontinuation of DVRd in more than 1 patient included sepsis
ALT=alanine aminotransferase; DVRd=DARZALEX FASPRO® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).
*Peripheral neuropathy includes neuropathy peripheral, peripheral motor neuropathy, peripheral sensorimotor neuropathy, and peripheral sensory neuropathy.1
†Includes other related terms.1
‡Upper respiratory tract infection includes fungal pharyngitis, h1n1 influenza, influenza, influenza-like illness, laryngitis, nasopharyngitis, oral candidiasis, oropharyngeal candidiasis, parainfluenzae virus infection, pharyngitis, respiratory moniliasis, respiratory syncytial virus infection, respiratory tract infection, respiratory tract infection viral, rhinitis, rhinovirus infection, sinusitis, tonsillitis, upper respiratory tract infection, viral tonsillitis, and viral upper respiratory tract infection.1
§Pneumonia includes bronchopulmonary aspergillosis, lower respiratory tract infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia influenzal, pneumonia klebsiella, pneumonia legionella, and pneumonia streptococcal.1
||Hepatotoxicity includes alanine aminotransferase increased, aspartate aminotransferase increased, hepatic cytolysis, hepatic failure, hepatic function abnormal, hepatoxicity, hyperbilirubinemia, hypertransaminasemia, and liver disorder.1
¶Only Grade 3 adverse reactions occurred.1
#Fatal adverse reactions included pneumonia: n=1 (0.3%) in the VRd arm.1
**Based on number of patients with a baseline and post-baseline laboratory value for each laboratory test.1
References:
- DARZALEX FASPRO® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
- Sonnenveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;390(4):301-313.
- Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab + bortezomib, lenalidomide, and dexamethasone (VRd) versus VRd patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplantation: Primary results of the PERSEUS Trial. Oral presentation at: 65th American Society of Hematology (ASH) Annual Meeting; December 9-12, 2023; San Diego, CA.
- Dimopoulos MA, Sonneveld P, Rodriguez-Otero P, et al. Daratumumab (DARA)/bortezomib/
lenalidomide/
dexamethasone (D-VRd) with D-R maintenance in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): Analysis of PERSEUS based on cytogenetic risk. Oral presentation at: American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL. - Data on file. Janssen Biotech, Inc.