Despite evidence from a large, randomized trial in favor of a low-dose regimen, some experts are reluctant to abandon high-dose therapy in newly diagnosed multiple myeloma patients.
A phase III study by the Eastern Cooperative Oncology Group in patients with newly diagnosed multiple myeloma showed that induction therapy with low-dose dexamethasone(Drug information on dexamethasone) plus lenalidomide (Revlimid) improved survival, compared with high-dose dexamethasone plus lenalidomide. Moreover, the low-dose regimen incurred fewer side effects and was easier for patients to tolerate.
Grade 3 or higher toxicity was 50% in the high-dose dexamethasone arm vs 30% in the low-dose arm. Deep vein thrombosis occurred in 25% vs 9%, respectively. Neutropenia was slightly higher in the low-dose arm (8% vs 19%, respectively), but more serious infections were seen in the high-dose arm: 19% vs 8%, respectively. There were more deaths within the first four months of the trial in the high-dose group: 5% vs 0.5%.
Despite this evidence from a large, randomized, controlled trial with 445 treatment-naïve patients, some experts are reluctant to abandon high-dose dexamethasone in newly diagnosed multiple myeloma.
Lead author of the ECOG trial, S. Vincent Rajkumar, MD, professor of medicine at the Mayo Clinic in Rochester, Minn., espouses the benefits of low-dose dexamethasone. Sagar Lonial, MD, associate professor of hematology and medical oncology at Emory University in Atlanta, argues that high-dose dexamethasone should not be abandoned, especially in selected patients.
Rationale for low-dose dexamethasone
In an interview with Oncology News International, Dr. Rajkumar described the three principles that convince him that the low-dose option is preferable for newly diagnosed myeloma patients.
• The high-dose regimen is empiric. “Prior to the study I presented at ASH 2007, there were no studies comparing low- vs high-dose dexamethasone,” he said. “In fact, the ‘standard’ high-dose dexamethasone regimen is empiric, with no studies to support the specific need for high-dose dexamethasone or to show that it improves survival, compared with lower doses. We need to know the safe and effective dose of dexamethasone, as determined by a well-designed, randomized study.”
• The low-dose regimen has superior survival. The ECOG study is the only randomized trial designed to look at dexamethasone dosing as the variable, with other drugs in the regimen being the same, he said. The study showed that low-dose dexamethasone achieved superior short-term survival with much lower toxicity, Dr. Rajkumar noted. In addition, he said, endpoints like time to progression, progression-free survival, and response duration were similar, with a trend in favor of low-dose dexamethasone.
• The high-dose regimen is more toxic. If a more toxic treatment is used, it should be significantly better than a less toxic treatment, not just as effective, he said. “In the case of high-dose dexamethasone, it is not much better than low-dose dexamethasone, even in patients under age 65. In fact, it is the same or probably worse in terms of the endpoint that matters most—overall survival. No data show improved survival with high-dose dexamethasone,” Dr. Rajkumar stated.