CHICAGO -- Treatment with daratumumab (Darzalex) in combination with other agents dramatically reduced the risk of disease progression in multiple myeloma patients who'd undergone one or more prior lines of therapy, researchers said here.
The median progression-free survival (PFS) had not been reached after 12 months for daratumumab, an anti CD38 antibody, combined with bortezomib (Velcade) and dexamethasone versus a 7.2 month PFS for patients treated with bortezomib and dexamethasone (P<0.0001), said, of the University of Torino in Italy.
Action Points
- Treatment with daratumumab (Darzalex) in combination with other agents dramatically reduced the risk of disease progression in multiple myeloma patients who'd undergone one or more prior lines of therapy.
- Note that the most common treatment-emergent adverse events among those who received daratumumab-bortezomib-dexamethasone were thrombocytopenia, sensory peripheral neuropathy, and diarrhea.
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
"That represents a 61% reduction in the risk of progression or death," he said at the American Society of Clinical Oncology (ASCO) annual meeting.
"The depth of the treatment was also impressive," Palumbo told 鶹ý. The percentage of patients who achieved a complete response with daratumumab was 19% compared with 9% of patients treated with the two-drug combination (P=0.0012), while the percentage of patients who achieved a very good partial response was 59% and 29%, respectively (P<0.0001), he said.
About 83% of patients who were in the daratumumab regimen achieved an overall response to the treatment compared with 63% of the patients treated with two-drug combination, Palumbo said.
"Daratumumab-bortezomib-dexamethasone should be considered a new standard of care for relapsed or refractory multiple myeloma patients currently receiving bortezomib plus dexamethasone alone," he said. "The benefit of daratumumab-bortezomib-dexamethasone was maintained across clinically relevant subgroups."
"Here, we've seen what can happen for patients when we select the treatment based on a common target in multiple myeloma," said , ASCO president and moderator of an ASCO press conference. "The new treatment regimen appears to rapidly slow cancer growth in many patients."
The study affirms the efficacy in daratumumab that was seen in earlier, smaller clinical trials in this setting," said Vose, who is at the University of Nebraska in Omaha.
In the multicenter, randomized phase III trial, Palumbo's group enrolled patients diagnosed with multiple myeloma who had experienced recurrence or relapse despite treatment with one or more line of therapy. Baseline demographics and disease characteristics were well balanced, the authors wrote.
They assigned 251 individuals to daratumumab (16 mg/kg IV) until progression, along with eight cycles of bortezomib (1.3 mg/m3 by subcutaneous injection) and dexamethasone (20 mg orally or by IV). They assigned another 247 patients to eight cycles of bortezomib plus dexamethasone at the same dose. The trial's primary endpoint was PFS.
Palumbo said the safety profile of daratumumab plus two agents was consistent with daratumumab monotherapy and the double-agent. The most common treatment-emergent adverse events were:
- Thrombocytopenia: 59% for daratumumab-bortezomib-dexamethasone versus 44% for bortezomib-dexamethasone
- Sensory peripheral neuropathy: 47% versus 38%
- Diarrhea: 32% versus 22%
About 7% of the patients on the three-drug combination discontinued due to adverse treatment-emergent events compared with 9% of those on the two-drug treatment, Palumbo said. Infusion reactions were experienced by 45% of patients, and 98% of the reactions occurred with the first infusion. He said the reactions could be managed with supportive care.
"We've suspected for long time that CD38 is the major treatment target for multiple myeloma," he said, "but these results are unprecedented in this cancer. It's clear now that we'll be moving to a three-drug regimen with daratumumab as the standard of care."
In commenting on the study, , of the Levine Cancer Institute, Carolinas HealthCare System in Charlotte, N.C. told 鶹ý that "these results will have a profound impact on my practice. This is quite significant. We will now be adding a third class of drugs to our treatment regimens. This does change the dynamics of how will treat our patients. I would treat my patients who fit the profile of this trial with daratumumab upfront." Usmani was not involved in the study.
Disclosures
The study was sponsored by Johnson & Johnson-Janssen.
Palumbo disclosed no relevant relationships with industry.
Vose disclosed relevant relationships with Sanofi, Bio Connections, Acerta Pharma, Amgen, Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Incyte, Janssen Biotech, Kite Pharma, Novartis, Pharmacyclics, Seattle Genetics, and Spectrum Pharmaceuticals.
Usmani disclosed relevant relationships with Amgen, Celgene, Sanofi, Janssen, and Pharmacyclics.
Primary Source
American Society of Clinical Oncology
Palumbo A, et al "Phase III randomized controlled study of daratumumab, bortezomib, and dexamethasone versus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: CASTOR study" ASCO 2016; Abstract LBA4.