Progress in the Treatment of R/R Multiple Myeloma

Ravi Vij, MD, MBA:Treatment for relapsed/refractory [R/R] myeloma has evolved tremendously over the last several years. We now have a number of 3-drug regimens that we use in the relapsed/refractory space. Until a few years ago, it was fairly common to use 2-drug regimens at relapse. And I think that the shift to 3-drug regimens has been driven by a number of studies that have shown improved progression-free survival, and some have even shown an improved overall survival when you use a 3-drug regimen instead of a 2-drug regimen in patients with relapsed/refractory disease. So the prevailing 2-drug regimens used to be, once again, lenalidomide and dexamethasone, and bortezomib and dexamethasone. But now we would rarely give 2-drug regimens to patients unless there’s a fear of toxicity.

The 3-drug regimens that have become popular in the recent several years include Kyprolis with lenalidomide and dexamethasone, daratumumab with lenalidomide and dexamethasone, elotuzumab with lenalidomide and dexamethasone, and ixazomib with lenalidomide and dexamethasone. Also, the FDA recently approved a 3-drug regimen of pomalidomide with Velcade and Decadron. So there is no deficiency of regimens that we can turn to.

I think that the choice of a regimen has to be individualized to a patient’s situation. There is no single accepted standard of care that has evolved. Even within a physician’s practice, one chooses a regimen based on a particular patient’s desires and needs, to some extent. In that regard, in the patient that we have discussed here, the 75-year-old gentleman, often patients like this desire an all oral regimen. They desire, if possible, not to have to come to the doctor’s office to have an infusion of a drug every week. So in this patient, the choice of ixazomib/lenalidomide/dexamethasone was appropriate given the patient had a desire to take something that was oral.

What is also important to note is that in a patient with a 17p deletion, trials have shown that the 3-drug regimen of ixazomib/lenalidomide/dexamethasone does as well for patients who have the 17p deletion as for those who do not. And so, I think that this patient, treated with ixazomib/lenalidomide/dexamethasone, was able to maintain a quality of life that could have been disrupted by repeated physician visits. I will say that in the future, patients will always move on to the alternative. So if this patient has received ixazomib/lenalidomide/dexamethasone in second-line therapy, and we are hoping that his ability to tolerate treatment persists even beyond, people will certainly move on to one of the other 3-drug regimens that we just discussed.

Patients who are older and who are not transplant-eligible certainly have benefited from the advent of modern therapies. Their benefit may not be as marked as for the transplant-eligible population. In the transplant-eligible population, we will often be comfortable quoting median survivals approaching 10 years. I think for the transplant-ineligible patients, it’s often probably somewhere between 5 and 7 years, but that is still a dramatic improvement over what we were achieving just a decade and a half ago when median survivals of 3 years or so were often quoted. For patients who are able to tolerate these new drugs, I think they certainly are contributing tremendously to their improvement in outcomes.

Transcript edited for clarity.

Case: 75-Year-Old Man With Symptomatic R/R Multiple Myeloma

January 2015

• A 75-year-old man was diagnosed with multiple myeloma; R-ISS stage I
• PMH: hypertension; coronary artery disease post stent placement
• Patient was treated with lenalidomide + dexamethasone for 9 months; transplant-ineligible due to age and performance status
• Patient achieved a VGPR, discontinued treatment thereafter due to patient request

September 2018

• On routine follow-up 3 years later, patient presents with new-onset back pain and generalized fatigue
• Imaging: multiple new lytic lesions with compression fractures
• Laboratory results:
  • Hb, 10.7 g/dL
  • Ca²⁺, 9.3 mg/dL
  • Creatinine, 1.1 mg/dL
  • M-protein, 3.2 g/dL
• Cytogenetics/FISH: del (17p) discovered at relapse
• ECOG PS: 2