Welcome to Managing Myeloma, my name is Shaji Kumar. The treatment for myeloma has significantly evolved over the past decade, particularly so in the past few years with the emergence of several new classes of drugs, as well as highly effective combination therapies. Monoclonal antibodies in particular have significantly changed the treatment paradigm for multiple myeloma. Currently there are two monoclonal antibodies available for treating patients with multiple myeloma.
Elotuzumab is a monoclonal antibody that targets a protein called SLAMF7 on the surface of myeloma cells. It has been shown to be effective in combination with lenalidomide as well as in combination with bortezomib in patients with relapsed multiple myeloma. More recently there has been a trial called ELOQUENT-3 that looked at the combination of elotuzumab with pomalidomide and dexamethasone, comparing it with pomalidomide and dexamethasone, and demonstrated an improved response rate as well as improved progression free survival. The progression free survival with the triplet combination in patients with relapsed myeloma was about 10 months, compared to about 5 months for the pomalidomide/dexamethasone. The response rates were also twice as much with the triplet combination, compared with just pomalidomide and dexamethasone, and this combination was very well-tolerated with very low rates of discontinuation due to any adverse reactions. 1 This data recently lead to its FDA approval as well. 2
This is quite important because this improves the opportunity to use this combination in patients with relapsed disease. Elotuzumab in combination with lenalidomide and dexamethasone – even though it has been approved – has not been used as much, primarily because patients often tend to be refractory to lenalidomide by the time they get to their second line of treatment. By combining it with pomalidomide, this triplet can certainly be used even in patients who are refractory to lenalidomide, and improves upon the spectrum of patients in whom this combination can be used.
This is very relevant as the number of treatment options for myeloma has increased over the past few years. The current initial treatment for patients with newly diagnosed myeloma is often a combination of bortezomib/lenalidomide/dexamethasone, followed by a stem cell transplant if they are eligible, and then lenalidomide maintenance. The vast majority of patients, by the time they have their first relapse, either are relapsing on lenalidomide treatment (meaning they are refractory to that drug) or have been on treatment with lenalidomide for a considerable amount of time before they get to that first relapse. We are constantly looking at combinations that can be used in these patients that incorporate pomalidomide, the next generation of immunomodulatory drugs.
Now we have approval for several different drugs in combination with pomalidomide. Daratumumab and carfilzomib are already being used in combination with pomalidomide, and now we have the option of using elotuzumab as well in this setting. This is also particularly relevant in the next few years to come as daratumumab is increasingly being used in the newly diagnosed patient setting, so we would be looking at other drugs to combine with pomalidomide in the relapsed setting.
This data is quite timely in terms of allowing us to use this combination for these patients. Overall, the safety profile from the ELOQUENT-3 trial was very reassuring. Adverse reactions were not seen in a significant number of patients and most of the adverse reactions could be well-managed, and tended to be lower grade. I think this adds to the armamentarium of drugs and drug combinations that we have available for patients with relapsed disease.
1. Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab Plus Pomalidomide/ Dexamethasone (EPd) vs Pd for Treatment of Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Phase 2, Randomized Open-Label ELOQUENT-3 Study. EHA 2018. Abstract: LB2606.
2. Revised FDA label for elotuzumab: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761035s008lbl.pdf