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Optimal Regimen in Maintenance Therapy for Multiple Myeloma Remains Unclear According to NCCN Expert

Megan Martin, Communications Manager

Maintenance therapy for multiple myeloma is a common clinical practice, but questions remain about which agent to use as well as optimal dosage and duration. Steven Devine, MD, from The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute and panel member of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma, spoke of current recommendations for treatment as well as toxicity concerns during a presentation at a recent NCCN Congress.

"The concept of maintenance therapy has been validated in an era of novel agents and appears to provide benefit to both elderly patients as well as those who have undergone autologous stem cell transplant," said Dr. Devine.

The NCCN Guidelines® include three preferred maintenance therapy regimens; however the duration of therapy is not specified.

"Specific therapeutic decisions need to be guided by individual patient characteristics, including the presence of comorbidities and patient preference," explained Dr. Devine.

Based upon a number of studies indicating improved progression-free and overall survival, thalidomide (Thalomid®, Celgene Corporation) is listed as an NCCN Guidelines category 1 maintenance therapy option after autologous stem cell transplant in patients newly diagnosed with multiple myeloma.

Dr. Devine expressed concern about the cumulative toxicity of thalidomide including an increased risk for peripheral neuropathy.

"Lower doses of the agent seem to be better tolerated," said Dr. Devine. "Ultimately, the benefits and the risks of maintenance therapy with thalidomide should be discussed thoroughly with patients."

Dr. Devine also spoke to the effects of lenalidomide (Revlimid®, Celgene Corporation), another preferred maintenance therapy that appears to increase time to progression and prolongs progression-free survival in patients following autologous stem cell transplant.

"One trial even indicated that lenalidomide maintenance improves overall survival," noted Dr. Devine.

Although lenalidomide is associated with less neurologic toxicity compared to thalidomide, there is some concern based on trial data that it may increase the risk of secondary cancers in patients, warranting careful discussion with a patient prior to initiation of maintenance.

"The NCCN Guidelines Panel has given lenalidomide a category 2A level recommendation pending the publication of additional peer-reviewed studies and safety data," said Dr. Devine.

Novel bortezomib (Velcade®, Millennium: The Takeda Oncology Company) -based regimens used in the initial treatment of multiple myeloma are also being investigated as therapeutic options for maintenance.

Two trials evaluating the effect of bortezomib-based maintenance regimens following elderly patients who received bortezomib-based induction therapy, indicate that it is a safe and effective treatment for this population and improves response.

The NCCN Guidelines list bortezomib as one of the preferred maintenance regimens and have given it a category 2A designation.

"Toxicity remains a concern, especially in elderly populations," said Dr. Devine. "Although some new agents come across as less toxic, recent research continues to show that patients younger than 75 tend to tolerate maintenance therapies better than their older counterparts."

In conclusion, Dr. Devine emphasized the need for physicians to take into consideration several factors including, but not limited to, patient preference, cost, strength and applicability of available data, and risk of toxicity when making treatment decisions regarding maintenance in multiple myeloma. 

"Research should continue to focus on risk-adapted approaches and individualizing treatment to further help refine patient management," said Dr. Devine.