“The cause is hidden; the effect is visible to all.”  

Mike Horn

Multiple myeloma is a cytogenetically complex blood cancer of the plasma cell, and these
cytogenetic aberrations make it more difficult to treat. Cytogenetics is the study of the
bone marrow looking for changes in the chromosomes of the cancerous cells that are broken, missing, rearranged, or have multiples of chromosomes. These changes are characterized as duplications, deletions, or translocations. They have prognostic features to the treatment and the risk of developing relapse of myeloma.

Therapy that should be considered for high-risk cytogenetic abnormalities is a three or a four-drug induction protocol. The three-drug protocol would include a proteasome inhibitor (like bortezomib) with an immunomodulatory drug, an IMiD, (like lenalidomide) and dexamethasone. The four-drug protocol would include a proteasome inhibitor, an IMiD, dexamethasone and an anti-CD38 antibody (like daratumumab). This regimen would be followed by “consolidation” therapy which is treatment given for a short period of time after the stem cell transplant. This treatment would be the same drugs used for induction therapy. Maintenance would follow with one or two drugs, lenalidomide or lenalidomide plus daratumumab.

Outcome of the therapy would depend on the cytogenetic profile, biomarkers, kidney function, age, and the presence of circulating plasma cells in the blood from the bone marrow Additionally, minimal residual disease (MRD) has emerged as a strong predictor of prognosis in newly diagnosed multiple myeloma. MRD negativity is a predictor of progression free survival (PFS) and overall survival (OS) regardless of the cytogenetic risk.

Despite advances in treatment modalities, patients continue to have progressive disease, however, treatment options for multiple myeloma have significantly improved. There is a good number of potentials with CAR-T cell therapy, bispecific immunomodulatory (BiTEs) therapy, or new novel drugs. There is also hope that these new therapies combined with the ability to understand the code hidden inside the myeloma cell will improve outcomes for refractory disease.

John DeFlice
Follow me on Twitter @johnde1MYELOMA