PrECOG PrE1005 - Belantamab Mafodotin or Daratumumab With Bortezomib, Lenalidomide and Dexamethasone for Newly Diagnosed Multiple Myeloma

By Shaji K. Kumar, MD

@myelomaMD

The treatment of newly diagnosed multiple myeloma (NDMM) has evolved significantly in recent years with the introduction of quadruplet regimens, which typically combine an anti-CD38 monoclonal antibody (daratumumab or isatuximab) with bortezomib, lenalidomide, and dexamethasone. Depending on factors such as age, overall health, and patient preference, some patients then undergo autologous stem cell transplantation (ASCT). Following initial therapy, maintenance treatment is typically used to help keep the disease under control and prolong remission.

Despite these advances, relapse remains common. Although many patients achieve deep and durable remissions, most will eventually experience disease progression and require additional therapy. As a result, more effective frontline treatment strategies remain an important unmet need.

One promising advance is belantamab mafodotin (belantamab), a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate. In relapsed multiple myeloma, belantamab-containing regimens have improved progression-free survival (PFS) and overall survival (OS) when combined with pomalidomide or bortezomib, and a phase 3 trial demonstrated superior outcomes compared with daratumumab. The US Food and Drug Administration (FDA) has approved belantamab in combination with bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Belantamab-based combinations have also shown promise in early-phase studies of newly diagnosed multiple myeloma. Building on these findings, investigators are exploring the efficacy of a novel quadruplet regimen that substitutes belantamab mafodotin for the anti-CD38 monoclonal antibody typically used in frontline therapy. The phase 3 PrE1005 trial, conducted by PrECOG, LLC, is designed to evaluate this approach in patients with newly diagnosed multiple myeloma who are ineligible for ASCT or have elected to defer transplantation.

Patients who enroll in PrE1005 will be randomly assigned to receive one of two treatment regimens:

·       Belantamab mafodotin-bortezomib-lenalidomide-dexamethasone (BVRd)

·       Daratumumab-bortezomib-lenalidomide-dexamethasone (DVRd)

Participants will continue with treatment until their disease progresses or side effects become too severe. All patients will be followed for up to 7 years.

One known side effect of belantamab is ocular toxicity. To help monitor and manage this risk, patients receiving the drug will undergo regular eye examinations throughout the study. In addition, the trial uses a lower-intensity belantamab dosing schedule than those evaluated in earlier studies, which investigators anticipate may reduce the incidence and severity of ocular side effects.

The primary objectives of PrE1005 are to determine whether BVRd is superior to DVRd in achieving minimal residual disease (MRD)-negative complete response (CR) and in improving PFS in patients with newly diagnosed multiple myeloma.

To be eligible for the study, patients must have suspected or confirmed newly diagnosed multiple myeloma according to International Myeloma Working Group criteria and must not have received more than one cycle of prior myeloma therapy. Patients must either be considered ineligible for ASCT by their treating physician or be eligible for ASCT but planning to defer transplantation until first relapse or a later time point.

Learn more about PrECOG PrE1005 at ecog-acrin.org.

Dr. Kumar (Mayo Clinic) is the study chair for this trial. The co-chair is Sagar Lonial, MD (Emory University/Winship Cancer Institute).