Although Multiple Myeloma (MM) remains as a potential incurable disease, important advances are occurring in the knowledge of the disease as well as in the treatment and management and as result, the overall survival is significantly improving. This benefit is applicable along the course of the disease, but the first line of therapy is crucial because almost 100% of patients will receive the first line of therapy and this is the place where patients will get the maximum benefit.
The deeper the response, the longer the progression free and overall survival and patients therefore should receive the combinations of therapies resulting in the highest rates of complete response or undetectable measurable residual disease using sensitive techniques for its detection inside and outside of the bone marrow. This is applicable to both transplant and non-transplant eligible patients and this distinction should be based on biological age together with comorbidities more than in the classical chronological age.
For transplant eligible newly diagnosed MM patients, the treatment should include induction followed by high-dose therapy and autologous stem cell transplantation and maintenance. Induction should include three-drugs based combinations (proteasome inhibitor plus immunomodulatory drug and dexamethasone) and now it is possible to add the monoclonal antibodies targeting CD38 daratumumab to the combination of VTd. Melphalan at high doses followed by transplant has demonstrated to upgrade the response and it results as a complementary rather than an alternative strategy, although in the future risk cytogenetic together with the depth of response will be introduced in the algorithm and some patients could not need transplant. Consolidation might be considered if the response previously achieved could be upgraded and maintenance will be able to maintain the response achieved and under the lenalidomide platform, new combinations are emerging like lenalidomide plus either daratumumab or carfilzomib.
In the setting of transplant ineligible patients, the old standards of care bortezomib, melphalan and prednisone and continuous therapy with lenalidomide and dexamethasone have been replaced by daratumumab plus either VMP or Rd because the addition of daratumumab significantly improved the responses rate including complete responses and undetectable measurable disease but also the outcomes in terms of progression free and overall survival. Bortezomib, lenalidomide and dexamethasone is another combination maybe of choice for fit patients and the platform to which monoclonal antibodies anti CD38 are going to be added.
