What is the treatment for Multiple Myeloma using Daratumumab (Darzalex) (Monoclonal Antibody) and other therapies?

From the Guidelines

DVd (Daratumumab, Velcade, dexamethasone) is a recommended treatment regimen for multiple myeloma patients who are refractory to lenalidomide, while DRd (Daratumumab, Revlimid, dexamethasone) is recommended for patients who are refractory to bortezomib. The choice of treatment depends on the patient's previous therapy and resistance status 1. For patients who have relapsed while receiving lenalidomide maintenance, or soon after discontinuing lenalidomide, DVd or ICd can be considered 1. On the other hand, patients who have relapsed while receiving bortezomib maintenance can be treated with IRd or DRd 1.

Some key points to consider when treating multiple myeloma include:

• The importance of considering the patient's previous therapy and resistance status when selecting a treatment regimen 1
• The use of combination therapies, such as DVd or DRd, which have been shown to be effective in treating multiple myeloma 1
• The need for regular monitoring of blood counts, renal function, and disease response throughout therapy 1
• The potential for toxicity and the need for prophylactic medications to prevent complications such as herpes zoster, pneumonia, and thrombosis 1

According to the most recent guidelines, the treatment of relapsed/refractory multiple myeloma has evolved to include several new options, including new combinations with second-generation proteasome inhibitors, immunomodulators, monoclonal antibodies, CAR T cells, bispecific antibodies, selinexor, venetoclax, and many others 1. Selecting treatment options for relapsed/refractory multiple myeloma requires consideration of resistance status to specific classes, and patient-specific factors such as age and other comorbidities should be considered 1.

In terms of specific treatment regimens, DVd has been shown to be effective in patients who are refractory to lenalidomide, with an overall response rate of 83% and a median PFS of 7.2 months 1. DRd has also been shown to be effective in patients who are refractory to bortezomib, with an overall response rate of 93% and a median PFS of 20.6 months 1.

Overall, the treatment of multiple myeloma requires a comprehensive approach that takes into account the patient's previous therapy, resistance status, and individual factors, as well as the latest evidence-based guidelines and treatment options.

From the FDA Drug Label

DARZALEX is indicated for the treatment of adult patients with multiple myeloma: in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant. in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant. in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. in combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.

Daratumumab (DARZALEX) is a treatment option for multiple myeloma. The recommended treatment regimens include:

• Combination with lenalidomide and dexamethasone for newly diagnosed patients ineligible for autologous stem cell transplant and for patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
• Combination with bortezomib, melphalan, and prednisone for newly diagnosed patients ineligible for autologous stem cell transplant.
• Combination with bortezomib, thalidomide, and dexamethasone for newly diagnosed patients eligible for autologous stem cell transplant.
• Combination with bortezomib and dexamethasone for patients who have received at least one prior therapy.
• Combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
• Combination with pomalidomide and dexamethasone for patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
• As monotherapy for patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent 2.

From the Research

Daratumumab Treatment for Multiple Myeloma

• The treatment of multiple myeloma with daratumumab has been evaluated in several studies 3, 4, 5, 6, 7.
• Daratumumab, a human IgGκ monoclonal antibody, targets CD38 and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma 4.
• The GRIFFIN trial evaluated the addition of daratumumab to lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible newly diagnosed multiple myeloma patients, and found that the addition of daratumumab improved the depth of response in patients with transplant-eligible newly diagnosed multiple myeloma 3.
• Another study found that the addition of subcutaneous daratumumab to bortezomib, lenalidomide, and dexamethasone (VRd) induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma 5.
• A cost-effectiveness analysis found that neither daratumumab, lenalidomide, and dexamethasone (DRd) nor bortezomib, lenalidomide, and dexamethasone (VRd) were cost-effective compared to lenalidomide and dexamethasone (Rd) in patients with multiple myeloma ineligible for autologous stem cell transplant 6.
• The MASTER trial combined daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) in newly diagnosed multiple myeloma, using minimal residual disease (MRD) by next-generation sequencing (NGS) to inform the use and duration of Dara-KRd post-autologous hematopoietic cell transplantation (AHCT) and treatment cessation in patients with two consecutive MRD-negative assessments 7.

Efficacy of Daratumumab

• The studies found that daratumumab improved the depth of response in patients with multiple myeloma, with improved rates of complete response, very good partial response, and minimal residual disease negativity 3, 4, 5, 7.
• The addition of daratumumab to RVd or VRd improved progression-free survival in patients with newly diagnosed multiple myeloma 3, 5.

Safety of Daratumumab

• The studies found that the addition of daratumumab to RVd or VRd was associated with increased rates of grade 3/4 hematologic adverse events, infections, and infusion-related reactions 3, 4, 5.
• However, the studies also found that the addition of daratumumab did not result in new safety concerns, and that the safety profile of daratumumab was consistent with previous studies 3, 5.