Treatment Options for Transplant-Ineligible MM

Keith Stewart, MB, ChB:For patients who are ineligible for transplant, a triplet regimen tends to be preferred today. The same regimen we use in younger patients, or VRd, which is bortezomib, lenalidomide, and dexamethasone, can be commonly employed at lower doses, something we call VRd [bortezomib, lenalidomide, dexamethasone]—lite, in which we would use subcutaneous weekly bortezomib. We would use a lower dose of lenalidomide, probably 15 mg, and particularly important, we would reduce the dosage of dexamethasone to 20 mg once weekly.

Alternatively, the combination of lenalidomide and dexamethasone alone, particularly for older patients who can’t travel easily to a center for an injection, that would be acceptable. Increasingly, however, and as we’ll discuss shortly, the introduction of the monoclonal antibody targeting CD38, daratumumab, has now been approved as an option in 2 different circumstances, particularly in the nontransplant-eligible patient.

Some of the decision factors that go into selecting a therapy for a transplant-ineligible patient include distance from the treating center and the ease by which the patient can come to the treatment center. Do they have transportation? Are there family members that can accompany them? Is parking an issue? Is mobility of the patient an issue to physically come into the treatment center to receive either an intravenous or a subcutaneous injection? That becomes 1 of the dominant factors in choosing a therapy in an older, more fragile patient.

In addition to that, we have to look at things like renal function, because there are certain suggestions that using lenalidomide in a patient with poor renal function may not be advisable. We have to look at preexisting conditions like diabetes or presence of peripheral neuropathy, which might lean against the use of bortezomib. Many of the factors we use both in the young becomes important in selecting the initial treatment. I think the addition of frailty, mobility, and family support become increasingly important as patients get older.

For patients who are transplant ineligible today, although the use of VRd [bortezomib, lenalidomide, dexamethasone] lite, or lenalidomide-dexamethasone, is very acceptable. People have become quite excited about the potential for using the monoclonal antibody daratumumab, or Darzalex, in this patient population. Two large phase III clinical trials have recently addressed the use of daratumumab as a frontline therapy in a nontransplant-eligible population.

The rationale for using a monoclonal antibody in this setting, of course, is it brings a new biology, a new biologic partner to the drugs that we already have. There are multiple mechanisms of action of the monoclonal antibody daratumumab. It’s not clear which is most important, but what we do know is a single agent, and in combination with other drugs, it is very active. It can be combined quite easily and, most important, particularly in the older patient, it’s really a point of benign toxicity profile. We’ll talk a little about what some of the issues are, but overall it’s a very well-tolerated drug.

Transcript edited for clarity.

Case: 83-Year-Old Man With NDMM Ineligible for Transplant

History and Presentation:

• 83-year-old man c/o back pain and fatigue
• Cardiac stent placed 3 years ago; high blood pressure; BMI 32

Diagnostic Workup:

• Laboratory findings
  • M-protein 3.8 g/dL
  • Hb 7.9 g/dL
  • LDH 290 IU/L
  • Albumin 3.9 g/dL
  • β2-microglobulin 4.25 mg/L
  • Creatinine 1.5 mg/dL
  • FLC kappa 134 mg/dL

• Bone marrow biopsy
  • Good cellularity with 60% bone marrow plasma cells
• Cytogenetics/FISH: standard-risk, no cytogenetic abnormalities
• Imaging
  • MRI of the spine: multiple focal lesions; moderate diffuse infiltration of spine, pelvis, and proximal femurs.
• ECOG PS: 2
• Durie-Salmon PLUS Stage IIIA IgG multiple myeloma requiring treatment with symptomatic anemia and bone lesions

Treatment:

Patient was started on D-Rd