Transplant-Ineligible MM: Future Directions and Unmet Needs

Keith Stewart, MB, ChB:The typical follow-up for a patient, particularly an older patient who is going to receive daratumumab, is standard. It’s usually at least monthly, but perhaps a little more frequently the first couple of months. We would be looking for very deep responses with this regimen, particularly looking to see if MRD [minimal residual disease] negativity can be obtained, which is the case in about 25% of patients in the MAIA study who underwent this regimen became MRD negative. That could be tested 2 ways: either by flow cytometry or by sending out the test for next-generation sequencing.

For the patients who progress after a daratumumab-containing regimen, this is an area where we really don’t have a lot of good data. Obviously, the drug has been stopped; it could be restarted. There’s lots of evidence to use daratumumab in combination with either bortezomib, lenalidomide, or pomalidomide at first relapse.

Other alternatives might be switching to a different monoclonal antibody. We just don’t have good data yet on use of drugs like elotuzumab in this setting, or using a nonmonoclonal antibody—containing regimen such as carfilzomib in combination with lenalidomide and pomalidomide, or reusing bortezomib again as a second line.

Although daratumumab is a very potent and effective drug in combination, 1 has to remember it does require a weekly intravenous infusion, and that may not be suitable for all older patients when an oral-based regimen might be appropriate.

The company that’s developed daratumumab is now significantly engaged in trying to make a more convenient schedule, particularly exploring the use of subcutaneous daratumumab. While this is still in the clinical trial phase, I think it will certainly make life a lot easier, particularly for older patients who can come in just for a subcutaneous injection as opposed to intravenous delivery.

For these transplant-ineligible patients, if we look at what’s on the horizon, I certainly think we’re quite eager to see the results of that elotuzumab-based phase lll clinical trials, which should report out soon. We’re also interested in how ixazomib with lenalidomide-dexamethasone, and perhaps even in a 4-drug cocktail with lenalidomide, dexamethasone, and daratumumab will perform. The early results look very promising for basically an all-oral regimen with the exception of daratumumab. These are 2 of the new advances in up-front treatment that we’re quite excited to see: ixazomib-elotuzumab with and without daratumumab.

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