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Posted by on Aug 27, 2023 in Multiple Myeloma | 0 comments

In a nutshell

This study evaluated the long-term effectiveness and safety of daratumumab (D; Darzalex) plus bortezomib (V; Velcade) and dexamethasone (d; Decadron) (D-Vd) regimen in patients with relapsed or refractory (r/r) multiple myeloma (MM). The data showed that the D-Vd regimen significantly increased the overall survival in these patients.

Some background

Multiple myeloma (MM) is a type of cancer that comes from blood cells called plasma cells. A high number of patients with MM experience relapse (the tumor grows after treatment) or are refractory (not responsive to the treatment) to standard treatment. Currently, the treatment strategies for r/r MM are based on the different combinations of conventional drugs and novel drugs. The standard treatment combinations for r/r MM are pomalidomide (Pomalyst) in combination with dexamethasone (Pd) and bortezomib in combination with dexamethasone (Vd).

Bortezomib is a proteasome inhibitor. Proteasomes are large molecules present in all body cells. They break down and remove damaged proteins. Bortezomib blocks the action of proteasomes, therefore preventing cancer cells from growing and multiplying. Daratumumab is an immunotherapy drug that directly targets the cancer cells to kill them. In a short-term study, daratumumab combined with bortezomib and dexamethasone (D-Vd) has been previously shown to improve the survival without cancer worsening in patients with previously treated r/r MM in the short-term. However, the long-term effectiveness and safety of D-Vd regimen in patients with r/r MM are still unknown.

Methods & findings

This study involved 498 patients with r/r MM who had been previously treated. Patients were randomly assigned into two groups. Group 1 included 251 patients who received the D-Vd regimen. Group 2 included 247 patients who received the Vd regimen alone. The average follow-up time was 72.6 months.

The average overall survival was 49.6 months in group 1 versus 38.5 months in group 2. This difference was statistically significant. Patients in group 1 were 26% more likely to have a better overall survival than patients in group 2.

The most common treatment-related serious side effects were low platelet counts (46.1% in group 1 vs. 32.9% in group 2), low red blood cell counts (16% in group 1 vs. 16% in group 2), low white blood cell counts (13.6% in group 1 v 4.6% in group 2), and pneumonia (10.7% in group 1 vs 10.1% in group 2).

The bottom line

This study concluded that the D-Vd regimen significantly increased the overall survival in patients with r/r MM in the long-term.

The fine print

This study was sponsored by Janssen Research & Development LLC, the manufacturer of daratumumab.

Published By :

Journal of clinical oncology

Date :

Nov 22, 2022

Original Title :

Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial.

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