Dr Sonneveld on the Background of the D-VRd Regimen in Newly Diagnosed Myeloma

Pieter Sonneveld, MD, PhD, professor, hematology, Erasmus University of Rotterdam, Erasmus Medical Center; chairman, HOVON Multiple Myeloma Working Group, European Myeloma Network, discusses the background of the phase 3 PERSEUS trial (NCT03710603), which evaluated the utility of daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Darzalex Faspro-VRd; D-VRd) for induction and consolidation in patients with newly diagnosed multiple myeloma.

the FDA granted approval to the combination

 for patients with newly diagnosed multiple myeloma who are also candidates for autologous stem cell transplant. Based on the trial results, patients treated with D-VRd (n = 355) had a significantly improved progression-free survival (PFS) vs VRd alone (n = 354; HR, 0.40; 95% CI, 0.29-0.57; 

 < .0001), and the median PFS was not yet reached in either treatment arm.

Traditionally, the standard therapy for this patient population, both in Europe and globally, has been VRd-like regimens, Sonneveld begins. However, with the advent of new data, particularly surrounding the anti-CD38 antibodydaratumumab, PERSEUS investigated whether adding this monoclonal antibody to the VRd regimen would enhance response rates and extend PFS, he explains.

PERSEUS was not the first time that daratumumab had been tested in multiple myeloma; the agent had already yielded promising results in the relapsed/refractory setting, he continues. Prior positive trials had explored its use in combination with bortezomib, thalidomide, and dexamethasone, Sonneveld explains. The PERSEUS trial, however, focused on incorporating daratumumab into the VRd regimen during the induction and consolidation phases, and evaluated its use in combination with lenalidomide during the maintenance phase, he emphasizes.

This approach offers significant advantages, Sonneveld expands. The VRd regimen is already recognized as highly effective, and the addition of daratumumab has the potential to further improve patient outcomes, according to Sonneveld. Moreover, the inclusion of daratumumab in the maintenance phase could be particularly beneficial, offering a promising strategy to enhance long-term results for patients with myeloma, he concludes.

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Pieter Sonneveld, MD, PhD, discusses the background of the PERSEUS trial, which evaluated D-VRd for induction and consolidation in newly diagnosed myeloma.

Dr Sonneveld on the Potential of Quadruplet Therapy Regimens in Multiple Myeloma

Pieter Sonneveld, MD, PhD, professor, hematology, Erasmus University of Rotterdam, Erasmus Medical Center; chairman, HOVON Multiple Myeloma Working Group, European Myeloma Network, discusses the feasibility of investigating quadruplet therapeutic regimens in the frontline treatment of patients with multiple myeloma.

the FDA approved daratumumab plus hyaluronidase-fihj

 (Darzalex Faspro) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Darzalex Faspro-VRd; D-VRd) for induction and consolidation therapy in patients with newly diagnosed multiple myeloma who are also candidates for autologous stem cell transplant. This regulatory decision was based on data from the phase 3 PERSEUS trial (NCT03710603). In the investigation, patients treated with D-VRd (n = 355) had a significantly improved progression-free survival (PFS) vs those who received VRd alone (n = 354; HR, 0.40; 95% CI, 0.29-0.57; 

 < .0001). Furthermore, the median PFS was not yet reached in either treatment arm.

At the 2023 ASH Annual Meeting, several new multiple myeloma regimens were discussed, 

, which combines isatuximab-irfc (Sarclisa), carfilzomib (Kyprolis), lenalidomide, and dexamethasone. This regimen has induced high response rates and rates of minimal residual disease negativity, Sonneveld begins. However, the follow-up period for this trial is still short, and there are no PFS data available yet. Nevertheless, this quadruplet regimen is promising, he reports.

With the advent of new immunotherapies, there is considerable potential for further enhancement of standard treatment strategies, he continues. For instance, investigators are currently studying frontline D-VRd followed by CAR T-cell therapy rather than an autologous transplant in patients with multiple myeloma. D-VRd is particularly favorable for combination with other innovative immunotherapy approaches and CAR T-cell therapies due to its good tolerance and high efficacy, Sonneveld states. These combinations may be used during induction and consolidation phases, as well as for maintenance therapy, he reports.

Overall, these developments could significantly enhance the efficacy and durability of treatment responses for patients, Sonneveld concludes.

Pieter Sonneveld, MD, PhD, discusses the potential of quadruplet therapeutic regimens in the frontline management of multiple myeloma.

Dr Sonneveld on the FDA Approval of Subcutaneous Daratumumab Plus VRd in Myeloma

Pieter Sonneveld, MD, PhD, professor, hematology, Erasmus University of Rotterdam, Erasmus Medical Center; chairman, HOVON Multiple Myeloma Working Group, European Myeloma Network, discusses the FDA approval of daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Darzalex Faspro-VRd; D-VRd) for induction and consolidation in patients with newly diagnosed multiple myeloma who are also candidates for autologous stem cell transplant.

the regulatory agency granted approval to the

 based on data from the phase 3 PERSEUS trial (NCT03710603). In the investigation, patients treated with D-VRd (n = 355) had a significantly improved progression-free survival (PFS) vs VRd alone (n = 354; HR, 0.40; 95% CI, 0.29-0.57; 

This regimen has generated a remarkably high response rate, with many patients achieving complete responses or better, Sonneveld begins. Additionally, the rate of minimal residual disease (MRD) negativity continues to increase as patients progress from initial treatment into the maintenance phase. Notably, the maintenance phase has been well tolerated, he explains. Patients have the option to discontinue daratumumab after 2 years, continuing with lenalidomide alone if they have achieved sustained MRD negativity, Sonneveld reports.

This combination of high efficacy and tolerability positions the regimen as an ideal candidate for standard-of-care treatment, he continues, and it has already become the standard in several European countries. The hope is that other countries in Europe will soon adopt this regimen as well, replacing older treatments that do not include daratumumab, Sonneveld advocates. The introduction of this regimen represents animprovement in both prognosis and quality of life for patients with newly diagnosed multiple myeloma, offering benefits for the future, according to Sonneveld.

Although it’s too early to determine the long-term overall survival rates, the current evidence strongly supports this regimen as a superior choice for standard care worldwide, he states. Further improvements may arise, but for now, this approach is a major step forward, Sonneveld concludes.

Pieter Sonneveld, MD, PhD, discusses the FDA approval of daratumumab plus VRd for select patients with newly diagnosed multiple myeloma.

Pieter Sonneveld, MD, PhD, head of the Department of Hematology, Erasmus University Medical Center, discusses how the incorporation of genomic profiling will play into the overall management of patients with multiple myeloma.

Gene expression profiling should be introduced as a predictor in clinical trials to identify patients with high-risk disease, Sonnevald explains. This represents approximately 15% to 20% of patients with multiple myeloma.

If identified properly, these patients can be selected for different treatment modalities. This is becoming easier, he explains, with the various therapies now FDA approved in this setting.

Dr. Sonneveld on Incorporating Genomic Profiling Into Myeloma Management

Pieter Sonneveld, MD, PhD, Head of the Department of Hematology, Erasmus University Medical Center, discusses the SKY92 prognostic indicator (MMPROFILER) for multiple myeloma.

Sonneveld and his team collected the DNA of tumors cells of more than 350 newly diagnosed patients with multiple myeloma. They then worked to identify which genes were overactive in the tumor cells of those patients and did a principal component analysis to find out what the most important genes that are relevant for the prognosis of those patients.

Ninety-two genes were identified that represent important pathways in multiple myeloma biology, says Sonneveld. Based on this data, a tool was created that can be used to predict the prognosis of individual myeloma patients or cohorts of patients in large clinical trials.

Pieter Sonneveld, MD, PhD

Articles

Dr Sonneveld on the Background of the D-VRd Regimen in Newly Diagnosed Myeloma

Dr Sonneveld on the Potential of Quadruplet Therapy Regimens in Multiple Myeloma

Dr Sonneveld on the FDA Approval of Subcutaneous Daratumumab Plus VRd in Myeloma

Dr. Sonneveld on Incorporating Genomic Profiling Into Myeloma Management

Dr. Pieter Sonneveld on a Prognostic Indicator for Multiple Myeloma