All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the International Myeloma Foundation or HealthTree for Multiple Myeloma.
Join our
How to sequence BCMA-directed therapies in early relapsed/ refractory multiple myeloma
At the ESH 7th Translational Research Conference:
Multiple Myeloma
with Martin Kaiser, Mohamad Mohty, and Rakesh Popat
Saturday, October 5, 2024 | 09:10-10:10 CEST
Register nowThis independent educational activity is funded by GSK. All content is developed independently by the faculty. The funders are allowed no influence on the content of this activity.
The Multiple Myeloma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Multiple Myeloma Hub cannot guarantee the accuracy of translated content. The Multiple Myeloma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
Test your knowledge! Take our quick quiz before and after you read this article to find out if you improved your knowledge. Results help us to improve content and continually provide open-access education.
Bortezomib, lenalidomide, and dexamethasone (VRd) induction followed by autologous stem cell transplantation, VRd consolidation, and lenalidomide maintenance is currently considered the standard of care for patients with transplant-eligible newly diagnosed multiple myeloma (NDMM). However, new treatment directions are needed to further increase the depth of response and long-term disease control.
Daratumumab, a CD38 monoclonal antibody, is currently approved for use in several treatment regimens aimed at both transplant-eligible and non-transplant-eligible NDMM. Recently, the phase II GRIFFIN study (NCT02874742) investigated the addition of daratumumab to VRd induction and consolidation with lenalidomide maintenance for transplant-eligible NDMM. Results showed a greater depth of response and longer progression-free survival (PFS) compared with VRd and lenalidomide alone.
The randomized phase III PERSEUS trial (NCT03710603) subsequently investigated daratumumab in combination with VRd and lenalidomide compared with VRd and lenalidomide alone in patients with transplant-eligible NDMM. The primary results of the study were recently presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition by Sonneveld. We summarize the key points below.
Figure 1. PERSEUS study design*
d, dexamethasone; DARA, daratumumab; D-VRd, daratumumab + bortezomib + lenalidomide + dexamethasone; MRD, measurable residual disease; PD, progressive disease; PO, oral; R, lenalidomide; SC, subcutaneous; V, bortezomib; VRd, bortezomib + lenalidomide + dexamethasone.
*Adapted from Sonneveld.1
Table 1. Baseline patient characteristics*
Characteristic, % (unless otherwise stated) |
D-VRd |
VRd |
---|---|---|
Median age, years |
61.0 |
59.0 |
Male |
59.4 |
57.9 |
ECOG PS score |
||
0 |
62.3 |
65.0 |
1 |
32.1 |
30.5 |
2 |
5.4 |
4.5 |
3 |
0.3 |
0 |
ISS stage |
||
I |
52.4 |
50.4 |
II |
32.1 |
35.4 |
III |
15.5 |
14.2 |
Cytogenetic profile |
||
Standard risk |
74.4 |
75.1 |
Intermediate risk |
4.2 |
2.8 |
High risk |
21.4 |
22.0 |
MM diagnosis |
||
CRAB criteria only |
35.3 |
32.1 |
Biomarkers of malignancy only |
14.7 |
18.5 |
CRAB criteria and biomarkers of malignancy |
50.0 |
49.4 |
CRAB, calcium renal anemia bone; D-VRd, daratumumab + bortezomib + lenalidomide + dexamethasone; |
Figure 2. PFS and rates of a CR or better in patients treated with D-VRd vs VRd*
CR, complete response; D-VRd, daratumumab + bortezomib + lenalidomide + dexamethasone; PFS, progression-free survival; VRd, bortezomib + lenalidomide + dexamethasone.
*Adapted from Sonneveld.1
Figure 3. Rates of overall negative MRD at a sensitivity of 10−5, 10−6, and sustained negative MRD at 12 months*
D-VRd, daratumumab + bortezomib + lenalidomide + dexamethasone; MRD, measurable residual disease; VRd, bortezomib + lenalidomide + dexamethasone.
*Adapted from Sonneveld.1
Figure 4. Most common Grade 3–4 AEs experienced by ≥10% of patients in either treatment group*
AE, adverse event; D-VRd, daratumumab + bortezomib + lenalidomide + dexamethasone; VRd, bortezomib + lenalidomide + dexamethasone.
*Adapted from Sonneveld.1
These results, in combination with those of the GRIFFIN and CASSIOPEIA (NCT02541383) trials highlight a significant and meaningful clinical benefit in depth of response, PFS, and MRD negativity with D-VRd together with daratumumab and lenalidomide maintenance. The risk-benefit profile was also favorable. Together, these results demonstrate the potential of this regimen as a standard-of-care treatment for transplant-eligible patients with NDMM.
Your opinion matters
Subscribe to get the best content related to multiple myeloma delivered to your inbox