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Expert Evaluates Evolving Options in Newly Diagnosed Myeloma

Caroline Seymour
Published: Monday, Nov 19, 2018

Ravi Vij, MD
Ravi Vij, MD
Transplant remains the standard of care for eligible patients with newly diagnosed multiple myeloma, although the optimal induction regimen and value of consolidation is still debated, explained Ravi Vij, MD.

However, in patients who are ineligible for transplant, Vij noted that proteasome inhibitors and monoclonal antibodies are showing promise in the frontline setting and may obviate the need for melphalan altogether.

Although bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) is the preferred induction regimen, according to Vij, the combination of carfilzomib (Kyprolis), lenalidomide, and dexamethasone (KRd) has already entered the pipeline, following multiple studies that have demonstrated a deeper depth of response. The head-to-head trial comparing the 2 competing strategies has completed accrual and will likely read out within the next 2 years (NCT01863550).

In patients ineligible for transplant, a recent news release announced that results of the phase III MAIA trial showed that the addition of daratumumab (Darzalex) to lenalidomide and dexamethasone (DRd) decreased the risk of disease progression or death by 45% compared with lenalidomide/dexamethasone (Rd) alone. In the interim analysis of the MAIA study, the median progression-free survival (PFS) had not been reached with the triplet versus 31.9 months in the Rd arm (HR, 0.55; 95% CI, 0.43-0.72; P <.0001). 

This follows the May 2018 FDA approval of daratumumab in combination with bortezomib, melphalan, and prednisone for the treatment of patients with newly diagnosed disease who are ineligible for autologous stem cell transplant.

“We’re certainly making tremendous progress in the frontline treatment of multiple myeloma,” said Vij. “A lot of things that are going on in the relapsed/refractory space could also move into frontline development in the years to come, from promising new small molecules to perhaps, in the future, bispecific T-cell engagers and chimeric antigen receptor-T cell therapy.”

In an interview during the 2018 OncLive®  State of the Science SummitTM on Hematologic Malignancies, Vij, professor of Medicine, Division of Oncology, Section of Bone Marrow Transplant, Washington University School of Medicine in St. Louis, Siteman Cancer Center, discussed emerging treatment options for patients with newly diagnosed multiple myeloma.

OncLive®: Can you provide an overview of newly diagnosed multiple myeloma treatment?

Vij: We've made tremendous strides in the treatment of patients with multiple myeloma. The paradigm that has evolved for multiple myeloma is one of continuous therapy. [First, we need to] determine whether a patient is transplant eligible or not. Stem cell transplant remains the standard of care for eligible patients. Most institutions would deem a stem cell transplant to be part of their initial therapy given the superior PFS that continues to be demonstrated. The paradigm for transplant-eligible patients is to give an induction period of treatment, though the optimal induction regimen is not known. The most popular regimen is VRd, which was shown to be superior to lenalidomide and dexamethasone in a study conducted by the SWOG Cancer Research Network. Though that study was not meant for patients who were proceeding to get transplants, it informed the decision that the use of 3 drugs is better than 2.

The use of our novel agents in the frontline setting is what continues to be explored. The substitution of bortezomib with carfilzomib is one thing that a lot of investigators are pursuing. Even off study, it has started to become a regimen that some institutions have adopted. The use of carfilzomib is primarily driven by studies that have shown a better depth of response when given with or without a transplant compared with what has been achieved historically. Frontline KRd is being compared with VRd in a randomized study, which has completed accrual. Hopefully, that will better inform our decision on which 3-drug regimen is optimal.

Very soon, we will probably move into the era of 4-drug treatments. The use of monoclonal antibodies and our 3-drug backbone is where the field is going to move. Daratumumab and elotuzumab (Empliciti) are both being explored in frontline trials. The trial data at this time are fairly preliminary. It is only a matter of time before 4-drug regimens best 3-drug regimens in comparative studies. Certainly, this will add to the cost of the regimen. However, some feel that the drug cost may be justifiable if one can give a finite period of therapy and thereby avoid the cost associated with the more extended therapy that we give today.




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