Darzalex (Daratumumab) Plus RVd Demonstrates Robust Efficacy in First-Line Treatment of Transplant-Eligible Newly Diagnosed Multiple Myeloma

April 26, 2020 /BioValleyBIOON/ -- Currently, for newly diagnosed multiple myeloma (NDMM) patients who are eligible for transplantation, after treatment with the lenalidomide, bortezomib, and dexamethasone regimen (RVd), autologousStem CellsAutologous stem cell transplantation (ASCT) is a standard first-line therapy. A recent study published in *Blood*, a top-tier journal in the field of hematology, demonstrated that compared with the RVd regimen, the combination of Johnson & Johnson’s anticancer drug Darzalex (Chinese brand name: ZHAOKE®; generic name: daratumumab) with RVd (D-RVd) significantly improved efficacy without introducing new safety concerns. The article is titled:Daratumumab, Lenalidomide, Bortezomib, & Dexamethasone for Transplant-eligible Newly Diagnosed Multiple Myeloma: GRIFFIN。

GRIFFIN (NCT02874742) is a randomized, open-label Phase II study conducted in patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose chemotherapy and autologous stem cell transplantation (ASCT), evaluating the efficacy and safety of the D-RVd regimen versus the RVd regimen. In this study, patients were randomized in a 1:1 ratio to two groups: one group received D-RVd induction (2 cycles), ASCT, D-RVd consolidation (2 cycles), and daratumumab plus lenalidomide maintenance therapy (26 cycles); the other group received RVd induction (2 cycles), ASCT, RVd consolidation (2 cycles), and lenalidomide maintenance therapy (26 cycles).

Results showed: In the primary endpoint analysis,At the end of consolidation therapy after ASCT, the stringent complete response (sCR) rate in the D-RVd group was higher than that in the RVd group (42.4% vs. 32.0%).; odds ratio [OR] = 1.57, 95% CI: 0.87–2.82; one-sided p = 0.068), meeting the prespecified one-sided α = 0.1.With prolonged follow-up (median: 22.1 months), remission continued to deepen, the sCR rate in the D-RVd group continued to improve compared with RVd (62.6% vs 45.4%; p=0.0177), in the intent-to-treat (ITT) populationMinimal Residual Disease (MRD) Negativity Rate (threshold: 10⁻⁵) Also Showed Improvement (51.0% vs. 20.4%; p < 0.0001). Disease progression occurred in 4 cases (3.8%) in the D-RVd group and 7 cases (6.8%) in the RVd group,The 24-month progression-free survival rates were 95.8% (D-RVd group) and 89.8% (RVd group), respectively.Grade 3/4 hematologic adverse events were more common in the D-RVd group. The incidence of infection was higher in the D-RVd group, but the rates of grade 3/4 infections were similar. The median CD34+ cell count was 8.2×10⁶/kg in the D-RVd group and 9.4×10⁶/kg in the RVd group, although plerixafor use was more prevalent in the D-RVd group. There was no difference in the median time to neutrophil and platelet engraftment.

In summary, compared with RVd, D-RVd induction and consolidation improved the depth of response in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), without new safety concerns or evidence ofStem CellsMobilization and engraftment have clinically significant effects.

Multiple Myeloma (MM) is an incurable hematologic malignancyTumor, characterized by alternating cycles of remission and relapse. This highly aggressive disease affects plasma cells in the bone marrow, where the abnormal plasma cells replace normal healthy cells. In 2020, an estimated 32,270 people were diagnosed with the disease, and 12,830 died from it. Although some patients with multiple myeloma (MM) are asymptomatic, most are diagnosed due to related symptoms, including fractures or pain, low red blood cell count, fatigue, hypercalcemia, renal problems, or infections.

Darzalex was first approved for marketing in November 2015. It is the first CD38-mediated, cytolytic antibody drug approved globally, possessing broad-spectrum cytotoxic activity. It targets and binds to the CD38 molecule, a transmembrane extracellular enzyme highly expressed on the surface of cells in multiple myeloma and various solid tumors. It induces rapid tumor cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), as well as throughApoptosis(apoptosis). In addition, Darzalex has also been shown to targetTumorImmunosuppressive cells in the microenvironment thus exhibit immunomodulatory activity.

In the United States, Darzalex has been approved for seven therapeutic indications, three of which are for first-line treatment. Currently, Darzalex has become a cornerstone therapy for the treatment of multiple myeloma (MM). The drug is indicated for first-line treatment of newly diagnosed MM patients (including those eligible and ineligible for autologous stem cell transplantation [ASCT]), as well as for second-line and later-line treatment of patients with relapsed or refractory MM.

In China,Darzalex (ZHAOKE®, daratumumab) was approved for market launch in October 2019., this drug is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma as monotherapy, specifically for those who have received prior therapies including proteasome inhibitors and immunomodulatory agents and experienced disease progression during their last treatment. AsChina's first approved CD38 monoclonal antibody targeted therapy,This innovative regimen is poised to redefine the treatment of multiple myeloma in China. (Bioon.com)

Original Source: Daratumumab, Lenalidomide, Bortezomib, & Dexamethasone for Transplant-eligible Newly Diagnosed Multiple Myeloma: GRIFFIN