Therapeutic Sequencing in Multiple Myeloma

One of the biggest challenges currently facing the treatment of patients with multiple myeloma is how to optimally sequence available therapies, says Jatin J. Shah, MD. Historically, the immunomodulatory agents and proteasome inhibitors have alternated in various sequences. A recent study examining the use of lenalidomide followed directly by pomalidomide showed a response rate of close to 30%. In order to maximally leverage all the therapies, it is important to think one step ahead about how the drugs will be sequenced, adds Shah.

In Europe, sequencing involves bortezomib-based combinations upfront, states Maria-Victoria Mateos, MD, PhD. In transplant candidates, a three-drug combination is usually used upfront. Lenalidomide plus dexamethasone is commonly used as a two-drug combination in the second-line setting, she says. In the third-line, the optimal approach is to either retreat with a bortezomib-based combination or move to a second-generation immunomodulatory drug, such as pomalidomide. This scenario will probably change in the near future, adds Mateos, as lenalidomide moves to earlier lines of therapy and as monoclonal antibodies become available.

The choice of sequence is driven by a number of factors, including the patient’s age, says Andrew Spencer, MD. In younger patients, he prefers to use a proteasome inhibitor, followed by a high-dose alkylating agent, and then an immunomodulatory drug. In elderly patients, other factors come into play, such as the distance the patient lives from the treatment center, explains Spencer.