Monday marked the last day of myeloma sessions at this year’s ASH meeting. The morning’s session on Initial Therapy gave us one study on the treatment for patients with smoldering multiple myeloma (SMM) and the remaining studies focused on various induction regimens for newly diagnosed multiple myeloma patients.
Smoldering Multiple Myeloma
Patients with active multiple myeloma typically have a preceding phase of disease referred to as either monoclonal gammopathy of undetermined significance (MGUS) or SMM (also called asymptomatic myeloma); collectively known as precursor conditions. Some SMM patients develop active myeloma much faster than others (ie, they are at higher risk of progression); identifying and treating these individuals earlier could potentially delay or event prevent that progression from occurring.
Investigators at the National Institutes of Health investigated the use of Kyprolis-Revlimid-dexamethasone (dex) followed by Revlimid maintenance in 52 patients with high-risk SMM (ABSTRACT 548). Their objective was to determine the rate of minimal residual disease (MRD) negativity in treated patients. Patients on this trial were defined as high risk by specific test results:
- 10% or more plasma cells in the bone marrow,
- M-protein of 3 gm/dL or higher, and
- Abnormal serum free light chain ratio
Following treatment, the results showed:
- MRD negativity was achieved in 70% of patients with a median duration of 5.5 years
- Only 10% of patients developed active myeloma after 8 years (compared historically to no treatment, which would have meant about 75% of patients would have developed active myeloma—this trial did not directly compare treatment to no treatment)
The investigators recommend future randomized trials (as this trial was only a single armed, phase 2 study) to confidently recommend this treatment for high-risk SMM patients.
Initial Therapy for Transplant Eligible Patients
The results of a study of a 4-drug combination of Darzalex-Revlimid-Velcade-dex (Dara-RVd) was recently published (here) showing that the addition of Darzalex to the standard induction therapy regimen of RVd significantly improved rates of stringent complete response (sCR) following autologous stem cell transplant (ASCT) and consolidation with more Dara-RVd.
Dr. Jonathan Kaufman of Emory University presented updated analysis from this trial to determine response rates following 1-year of maintenance therapy with either Revlimid alone or Revlimid-Darzalex (ABSTRACT 549). The results showed:
- Dara-RVd followed by Dara-Revlimid maintenance treatment continued to demonstrate deep and improved responses (including higher sCR and MRD negativity) compared to Revlimid alone
- MRD negativity rates were further improved following maintenance compared to following consolidation
Initial Therapy for Transplant Ineligible Patients
We now switch to a potential option for patients who are unable to receive an ASCT. In an international study, the combination regimen of Ninlaro-Revlimid-dex was compared with Revlimid-dex in 705 transplant-ineligible patients whose median age was 70 years or more (ABSTRACT 551). Patients were evenly divided between the treatment groups (Revlimid-dex with or without Ninlaro). The results showed that adding Ninlaro to Revlimid-dex revealed a trend towards longer time to disease progression than Revlimid-dex alone but was not considered a statistically significant difference between the treatment groups. The investigators concluded that Ninlaro-Revlimid-dex is a feasible treatment option for certain transplant-ineligible patients. Additionally, this would be an all-oral treatment regimen which could prove useful during times—such as we find ourselves today—when limiting hospital and clinic visits is necessary.
We’ll be back later with one more session overview before we close out our reporting from ASH 2020!
