Newly Diagnosed Myeloma Can Be Treated With Lower-Dose Dexamethasone

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Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials
Article Date: 22 Oct 2009 - 0:00 PDT

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A study published Online First by The Lancet Oncology reports that lenalidomide plus low-dose dexamethasone is linked to better short-term overall survival. In addition, it is associated with lower toxicity than lenalidomide plus high-dose dexamethasone in patients with newly diagnosed myeloma. Therefore it is a possible treatment option for these patients. Currently, high-dose dexamethasone is a basis of therapy for multiple myeloma. The article is the work of Professor S Vincent Rajkumar, Mayo Clinic, Rochester, MN, USA, and colleagues on behalf of the Eastern Cooperative Oncology Group (ECOG), USA.

All of the patients involved in this randomised controlled trial had untreated, symptomatic myeloma. They were assigned to receive lenalidomide 25 mg on days 1 to 21 plus dexamethasone 40 mg on days 1 to 4, 9 to12, and 17 to 20 of a 28-day cycle (high dose), or lenalidomide given on the same schedule with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle (low dose). After completing four cycles, patients could suspend therapy to follow stem-cell transplantation or continue treatment until disease progression. The primary endpoint was response rate after four cycles. It was evaluated according to the European Group for Blood and Bone Marrow Transplant criteria.

Results indicated that that 79 percent of 214 patients receiving high-dose therapy and 68 percent of 205 patients on low-dose therapy had complete or partial response within four cycles. But, at the second interim analysis after one year, overall survival was 96 percent in the low-dose dexamethasone group compared with 87 percent in the high-dose group. As a consequence, the trial was halted and patients on high dose therapy were crossed over to low-dose therapy. A total of 117 (52 percent) patients on the high-dose regimen had grade 3 or worse toxic effects in the first four months. This compared with 76 (35 percent) patients of the 220 on the low-dose regimen for whom toxicity data were available. In addition, 12 of 222 (5 percent) patients on high dose and one (<1 percent) of 220 on low-dose dexamethasone, died in the first four months. The three most common grade 3 or higher toxicities were:

• Deep-vein thrombosis: 57 (26 percent) of 223 versus 27 (12 percent) of 220.
• Infections including pneumonia: 35 (16 percent) of 223 versus 20 (9 percent) of 220.
• Fatigue: 33 (15 percent) of 223 versus 20 (9 percent) of 220.

The researchers explain: "High-dose dexamethasone in a community-setting seems more toxic than low-dose dexamethasone, with more early deaths in the first 4 months, increased risk of thromboembolic complications, and higher overall risk of serious adverse events, particularly in patients older than 65 years."

They write in closing: "This trial...shows that low-dose dexamethasone in conjunction with lenalidomide is an active regimen for newly diagnosed myeloma with acceptable toxicity and low early mortality."

They continue by saying: "The results of this trial show that the use of high-dose dexamethasone is not needed for the most part in the context of new active agents for myeloma, and as a result almost all current phase 3 trials have adopted low-dose dexamethasone as the standard in combination regimens."

In an associated comment, Professor Antonio Palumbo and Dr Francesca Gay, Divisione di Ematologia dell'Universita di Torino, Turin , Italy remark: "The high efficacy and good tolerability of lenalidomide plus low-dose dexamethasone as initial therapy for myeloma has thus been established."

They write in conclusion: "Further randomised phase 3 studies, comparing this regimen with current standards of care such as melphalan-prednisone-thalidomide or melphalan-prednisone-bortezomib, are still needed to verify whether lenalidomide plus low-dose dexamethasone can become a new standard of care for patients with myeloma, and whether the optimal therapeutic strategy should be long-term treatment with lenalidomide and steroids or short-term treatment followed by consolidation with autologous transplantation."

"Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial"
S Vincent Rajkumar, Susanna Jacobus, Natalie S Callander, Rafael Fonseca, David H Vesole, Michael E Williams, Rafat Abonour, David S Siegel, Michael Katz, Philip R Greipp, for the Eastern Cooperative Oncology Group
DOI: 10.1016/S1470-2045(09)70284-0
The Lancet Oncology

Written by Stephanie Brunner (B.A.)
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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