Advances in Hematologic Malignancies
Issue 9, Fall 2018
— Irene Ghobrial, MD
Multiple myeloma (MM) almost always progresses from precursor states of monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM). However, the progression risk for MGUS and SMM
to overt myeloma is highly variable. Some patients rapidly progress from MGUS/SMM to overt MM ("progressors") and have identifiable disease features that confer a risk of progression of up to 70% over 5 years; others are much more likely to remain
indolent and have a lower risk of progression over the same time period ("non-progressors"). Although many patients are diagnosed at earlier phases of disease, most patients do not receive treatment until their disease progresses to overt myeloma,
at which time they have overt end-organ damage.
This concept of initiating therapy at the time of symptomatic disease is analogous to initiating therapy in patients with solid tumors only after the development of measurable metastatic disease. It is therefore not surprising that cure is not achieved
for most patients with MM.
At the Center for Prevention of Progression (CPOP) at Dana-Farber Cancer Institute, we have launched a large effort to develop several clinical trials that focus on early interception of disease progression in multiple myeloma. Currently, we have the
largest effort in the U.S. that specifically focuses on early interventions in MGUS and SMM. These efforts include two large initiatives that focus on sample collection and data acquisition to help us understand mechanisms of disease progression in
these precursor conditions: the PCROWD study that enrolls patients who have precursor conditions; and more recently, the PROMISE study,
which aims to screen high-risk individuals who are at risk of developing MGUS or SMM.
Finally, we have several ongoing interventional clinical trials for patients with MGUS and SMM to help prevent disease progression. These include novel agents such as the combination of ixazomib, lenalidomide, and dexamethasone in high-risk SMM (clinicaltrials.gov NCT02916771) or immunotherapies such as daratumumab in high-risk MGUS and low risk SMM (clinicaltrials.gov NCT03236428). We are also enrolling on a phase 3 registration
study of daratumumab in high-risk SMM. In addition, we will soon be launching vaccine studies that target specific neoantigens in patients with high-risk SMM, paving the way for precision medicine in MGUS and SMM.
For a complete list of our clinical trials, please check the CPOP clinic on the Dana-Farber website, or email me with any
questions at firstname.lastname@example.org.
Our team has led many trials of combination therapies and novel agents to intercept multiple myeloma at the MGUS or precursor stage, and halt progression.