Nontransplant Treatment Approaches in Multiple Myeloma

Robert A. Vescio, MD:The decision to stop bortezomib and just continue with lenalidomide and dexamethasone often comes up, particularly in patients who are not transplant eligible. They generally get tired of coming in for their bortezomib shots. There are different ways of giving the treatment. You can give it more frequently at full strength, which is twice a week for 2 weeks out of 3, which is particularly inconvenient, or you can give it less aggressively—a once-a-week type of treatment, either 3 weeks out of 4 or even every week. People tend to do it differently. But ultimately, patients, in many cases, get tired of coming in. Even though it’s preferable to continue a treatment that’s working for as long as it’s working—and that would be my general recommendation—I also typically will not continue bortezomib because of the inconvenience of it. I work in a place in Los Angeles that’s hard to get to. It’s challenging enough for patients to arrive for their treatment. Other patients have no problem. I’ve had people take weekly bortezomib for 7 years. It can be done, but, in reality, patients don’t prefer it.

In a patient with high-risk cytogenetics, it’s particularly important to continue the proteasome inhibitor. A lot of these high-risk cytogenetics were determined to be high risk based upon the drugs that we had 15, 20 years ago. Certainly, 20 years ago, the list did not include proteasome inhibitors.

Proteasome inhibitors seem to negate many of the high-risk features, if they’re used, and often work just as well as therapy in patients with high-risk disease as they do for people with standard-risk disease. So, when somebody does have these high-risk features, there is even more of an argument to continue with a proteasome inhibitor.

The use of a proteasome inhibitor in somebody with high-risk disease is important. I am certainly fine continuing with bortezomib if patients are willing to come in. Often, for convenience’s sake, it’s given at a dose that is less than full strength. People often compare proteasome inhibitors based upon full strength. But, in reality, patients often don’t take full-strength bortezomib indefinitely—or, for that matter, carfilzomib indefinitely. One certain advantage of ixazomib is that swallowing a pill once a week, for 3 weeks out of 4, is very convenient. And so, patients often can take full-strength proteasome inhibition, at least with that medication, and continue on a full-strength regimen of that drug. I tend to offer patients ixazomib after they’ve received the VRd regimen as a way of continuing triplet therapy in a more convenient fashion.

One of the key terms that is frequently used in multiple myeloma is maintenance therapy. Patients love the wordmaintenance. They like the wordremission. Myeloma is a disease that we don’t think we can cure. Certainly, we don’t seem to cure it very often, so I think there’s been too much excitement over labeling a drug as a maintenance therapy. I think maintenance sometimes implies that it is less therapy. If a patient is taking treatment and it’s working, and it’s being tolerated, they should continue that therapy at the dose that is working. I try to avoid the use of the termmaintenance. I don’t diminish the dose of the drug just for the sake of diminishing the treatment. I’ll just reduce the intensity of the treatment based on side effects. Some patients don’t have side effects, despite using the full-strength dose of these drugs.

Transcript edited for clarity.

A 55-year-old African-American Woman With Relapsed Multiple Myeloma

August 2015

• A 55-year-old African-American woman presented to her PCP complaining of worsening fatigue, back pain, and bone pain
• PMH: hypertension managed on a beta blocker, mild renal impairment
• Laboratory results:
  • Hb, 11.0 g/dL;
  • Ca²⁺, 10.1 mg/dL;
  • Creatinine, 1.2 mg/dL;
  • M-protein, 0.9 g/dL
  • Β2M, 5.0 mg/L
  • Albumin, 2.9 g/dL
• MRI showed multiple small lytic lesions in the T1/T2 vertebrae
• Bone marrow biopsy confirmed the diagnosis of multiple myeloma; R-ISS stage II; t(4;14)
• She was treated with lenalidomide/bortezomib/dexamethasone (RVd) for 6 months and achieved a VGPR
• The patient was recommended for autologous transplant, however, she instead opted to continue on a de-escalated treatment regimen of Rd after stating that she struggled to maintain her treatment schedule

May 2018

• M-protein, May 1.5 g/dL

June 2018

• M-protein, 1.7 g/dL

July 2018

• MRI, no new lytic skeletal lesions
• Laboratory results:
  • Hb, 11.5 g/dL;
  • Ca²⁺, 9.8 mg/dL;
  • Creatinine, 1.1 mg/dL;
  • M-protein, 1.9 g/dL
  • Β2M, 4.2 mg/L
• ECOG PS: 0