According to a report in Myeloma Research News, the European Commission has recently granted authorization to market bortezomib, dexamethasone and thalidomide (collectively known as VTd) plus daratumumab to treat multiple myeloma patients who are newly diagnosed.
The authorization was based on the end results of Part 1 of a large Phase III clinical trial (CASSIOPEIA NCT02541383).
The CASSIOPEIA study is one of the largest stem cell transplant studies conducted in multiple myeloma.
The trial results indicate that after the initial rounds of therapy, the stringent complete response, which is deeper than a complete response, was twenty-nine percent for patients treated with the four-drug combination.
The results compared against twenty percent stringent complete response in the group of patients who received (VTd) alone.
Although the progression-free survival results were not reached, it was determined that the daratumumab plus VTd arm had a fifty-three percent risk reduction in disease progression or risk of death.
About Phase III CASSIOPEIA Clinical Trial (NCT02541383)
The ongoing CASSIOPEIA trial is being conducted to test the effects of daratumumab (Darzalex) combined with the standard three-drug therapy (the VTd combo).
The study is an open-label trial meaning that the clinicians and the patients are know what drug each individual patient is being given. The trial involved 1085 newly diagnosed but previously untreated multiple myeloma patients with the median age being 58.5 years.
The majority of patients (84.5%) had standard-risk myeloma and were eligible for high-dose chemotherapy and autologous stem cell transplant.
An autologous stem cell transplant utilizes healthy blood stem cells from the patient’s body. These stem cells replace the patient’s damaged or diseased bone marrow.
Eligibility also required that the patients’ performance status (daily living abilities) is rated between 0 and 2. This was measured using the standard ECOG scale.
Part 1 of the Trial
The endpoint of Part 1 of the trial is complete remission. Patients, who were randomly selected, received four cycles of initial therapy. Standard therapy (the VTd combination) was administered to 542 patients. The second arm of 543 patients received the daratumumab plus the standard VTd combination.
The drug therapy was administered to prepare the patients for stem cell transplant. This is followed by consolidation drug therapy which is therapy administered after the patient is in remission with no detectable signs of cancer.
In part two of the trial, all patients who responded to treatment were reassigned to either maintenance therapy, with daratumumab administered every eight weeks for two years; the others were simply kept on observation without additional treatment.
Phase III Intermediate Results
In October 2018 the company announced the Part 1 trial results. Pre-treatment with daratumumab plus the standard VTd combo increased the number of patients with no detectable signs of cancer from twenty to twenty-eight percent after stem cell transplant.
At eighteen months, the overall response rate of patients whose cancer decreased or disappeared after the consolidation therapy was ninety-two percent with daratumumab plus the standard VTd combo. The standard VTd combo alone showed an overall response rate of eighty-nine percent.
Adverse Events
Adverse events that were most frequently reported were nausea, fever, reaction to infusions, bronchitis, and upper respiratory infections.
Thirty-five percent of participants reported infusion reactions when receiving daratumumab.
About Daratumumab (Darzalex)
The antibody daratumumab blocks activity of CD38, which is a protein that binds to multiple myeloma cells. By blocking CD38, daratumumab prevents the growth of cancer cells and eliminates them.
The recent FDA approval of Darzalex (daratumumab) represents its seventh approval in the last four years. The drug was originally developed by Genmab. In August 2012, it was licensed to Janssen R&D LLC.
Janssen Pharmaceutical Companies are working in collaboration with the IMF Group and Dutch Belgian Group, HOVON.
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