Further study results from 2019, reported at the European Society of Hematology (EHA) meeting, were from the GEM-CESAR study as presented by Maria-Victoria Mateos. The GEM-CESAR study used induction therapy with carfilzomib, lenalidomide and dexamethasone (KRd) followed by high-dose melphalan (HDM), autologous stem cell transplant (ASCT) and subsequent consolidation and maintenance with KRd. This study showed 85% of patients with SMM maintained complete responses (CR), with a minimal residual disease (MRD) negativity rate of 68% at the KRd maintenance stage.
Results from two other clinical trials in high-risk SMM were presented during the American Society of Hematology (ASH) meeting in 2018. The first, a phase II trial, was presented by Irene Ghobrial, and discussed the use of elotuzumab, lenalidomide and dexamethasone to treat high-risk SMM. The study investigators found the triplet regimen to be well-tolerated, with a 95% progression-free survival (PFS) at 36 months post-treatment. The other trial was a phase II trial using ixazomib, lenalidomide and dexamethasone. Again, this study found the triplet regimen to have minimal toxicity and high response rates, with further studies ongoing.
The use of a PVX-410 vaccine, a human leukocyte antigen A2 multi-peptide cancer vaccine, has also been investigated in SMM, with results published in August 2018. The phase I/IIa study investigated PVX-410 with, and without, lenalidomide in a high-risk SMM population. The results indicated the vaccine can increase immunogenicity in a specific patient population, though larger trials are required.
Whilst the study results reported above show promise for early intervention methods in high-risk SMM, there is still much discussion ongoing regarding;
- When to intervene?
- Should intervention be intensive?
- Is observation sufficient in certain patients?
- How do we define patients at high-risk of progression?
When to intervene
These questions have been debated at recent meetings, including the 5th World Congress on Controversies in Multiple Myeloma (COMy) meeting, 2019, where Sundar Jagannath and Mario Boccadoro discussed the pros and cons of treating SMM early. Sundar Jagannath began by presenting the argument FOR early intervention, stating that it is important to treat early, to eradicate the disease and delay clonal evolution. Mario Boccadoro then presented the argument AGAINST treating early, saying that we need a consensus definition of high-risk SMM first, and that we need to identify the optimal treatment strategy as current trial results are contradictory. In a poll conducted by the MM Hub on Twitter following the debate, 53% of users agreed that SMM should be treated early.
The MM Hub also conducted its first ever expert discussion during the 2019 ASCO meeting, with Maria Victoria-Mateos and Francesca Gay debating when intensive treatment strategies should be used in SMM and NDMM. Both speakers are heavily involved in trials in the high-risk SMM population, and the newly diagnosed MM population, respectively, leading to an excellent debate addressing many important questions. Both concluded that intensive treatment strategies are feasible in both SMM and NDMM patient populations. They also agreed that treatment should be modified according to risk factors, to ensure treatment is optimal for each patient. This could form the beginning of personalized medicine in SMM and is likely to grow in coming years.