“What this study shows is basically the major benefit in older patients is still restricted to the most high-risk patients,” said Perl. “The most sizeable benefit was seen in the ELN-risk adverse group with not an obvious benefit for transplant, which is a little eye-opening, but I don’t know if it’s a definitive answer. This is likely a start for other groups to be reporting their experience with this.”
Curative strategy for high-risk smoldering myeloma (gem-cesar): carfilzomib (Kyprolis), lenalidomide (Revlimid) and dexamethasone (KRd) as induction followed by HDT-ASCT, consolidation with KRd and maintenance with Rd (Abstract 402)
This single-arm, phase II study evaluated the strategy of induction therapy with carfilzomib, lenalidomide, and dexamethasone followed by HDT-ASCT, consolidation therapy and then maintenance therapy with lenalidomide and dexamethasone for patients who have smoldering multiple myeloma who are at high risk of progression to multiple myeloma. Prior studies have shown that treatment with lenalidomide and dexamethasone early in a treatment course for these patients is likely to significantly improve PFS.
C. Ola Landgren, MD
“They only have a few patients who have completed all of the therapy, and so far the numbers look very familiar to the NCI study, but the key question will be long term,” shared C. Ola Landgren, MD, professor of medicine and chief of the Multiple Myeloma Service at Memorial Sloan Kettering Cancer Center. “Will there be a big difference if you add transplant or not in terms of efficacy? It’s too early, but this study will answer an important question: do you use the most aggressive treatment upfront?”Daratumumab monotherapy for patients with intermediate or high-risk smoldering multiple myeloma: CENTAURUS, a randomized, open-label, multicenter phase II study (Abstract 510)
Although the monoclonal antibody daratumumab (Darzalex) is approved as a monotherapy and in combination with standard regimens for patients with relapsed/refractory multiple myeloma, this phase II study evaluated the agent in patients with high-risk smoldering multiple myeloma in an effort to delay symptomatic progression to multiple myeloma (NCT02316106).
“The study has 2 coprimary endpoints, one endpoint is CR rate at 6 months, and the other one is PFS at 12 months,” said Landgren. “According to the abstract, there is a PFS difference already at 12 months of follow-up in this patient population. Maybe we should start thinking about early treatment.”Next-generation sequencing identifies smoldering multiple myeloma patients with a high risk of disease progression (Abstract 392)
The factors which are likely to cause patients with smoldering multiple myeloma or with monoclonal gammopathy of undetermined significance to progress to multiple myeloma have not been identified. Therefore, in this analysis, investigators used next-generation sequencing on clinically annotated samples of smoldering multiple myeloma at both the disease stage and at time of progression to determine what genetic factors may be associated with progression.
“This is an interesting study; they have close to 200 patients and have conducted whole-exome sequencing and whole-genome sequencing on a subset of patients,” Landgren discussed. “Really, the idea they have is to see whether you actually genetically can predict who is going to go into multiple myeloma. There is no study that, so far, has done that for us. This study doesn’t fully answer, but it provides a lot of new clues. It shows, for example, that mutational burden is higher in what we clinically refer to as high-risk smoldering myeloma.”Minimal residual disease (MRD) in multiple myeloma: final analysis of the IFM2009 trial (Abstract 435)
In the prospective IFM2009 trial, researchers conducted immunoglobulin gene next-generation sequencing to quantitate MRD and to correlate with PFS and OS in 700 patients who received RVD induction followed by high-dose melphalan or observation. All patients then received 1 year of maintenance treatment with lenalidomide. Investigators assessed MRD using the clonoSeq kit by Adaptive Biotechnologies.