Sagar Lonial, MD

Five years from now multiple myeloma will have a therapeutic backbone consisting entirely of combinations of novel agents, a leading myeloma researcher predicted.

The combinations will involve immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies. Stem-cell transplantation will retain a role in treatment of myeloma, but its role in the era of monoclonal antibodies will likely be a topic of multiple clinical trials.

“We will sequence patient samples after two to four cycles of therapy in order to understand the specifics of the remaining clone and how to target it,” Sagar Lonial, MD, chief medical officer at Winship Cancer Institute of Emory University said in a presentation at the 2015 Society of Hematologic Oncology annual meeting.

“This will guide maintenance therapy. Once patients become MRD [minimal residual disease] negative, they will be randomized to continue or stop therapy based on their genetics at presentation.”

Current therapeutic approaches based on diagnostic tissue specimens may help guide treatment over the short term but may not reveal that clone that will be present at relapse, Lonial said. Recent studies have shown that myeloma is a disease consisting of both normal and malignant-cell biology, and treatment should target both types of biology.

“MRD, in and of itself, does not indicate cure, but is needed on the path to cure,” he said.

In the not-to-distant future, RNA sequencing will become standard diagnostic testing at the initial evaluation of a patient with myeloma, replacing both fluorescence in situ hybridization and gene expression profile. RNA sequencing at presentation may not be reflective of myeloma genetics at relapse, so reassessment will be required when the disease burden has decreased and will be helpful in guiding maintenance therapy, said Lonial.

Three classes of drugs will form the basis of initial treatment for all patients: immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies. On the basis of biomarker or mutation findings, some patients might receive other classes of therapy. Potential options might include histone deacetylase inhibitors; kinesin spindle protein inhibitors; Myc-targeted therapy; and agents targeting the apoptosis pathway, CRM, or Akt.