Proteasome Inhibitors in Upfront MM Treatment

Ravi Vij, MD:The patient in this illustration is between 70 and 80 years of age. Most of the patients in my practice, between 70 and 80, who are not transplant-eligible, are able to tolerate a 3-drug regimen. I think that in my own practice, therefore, I would probably—as noted before—have treated this patient with a 3-drug regimen of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone because I believe that it produces greater depth of response, which usually leads to long-term outcomes being better.

In the patient who is not transplant-eligible, we don’t have any data on VRD-lite. We do, however, have data from patients who are not proceeding on to stem cell transplant, with full intensity regimen of Velcade, Revlimid, and Decadron (dexamethasone), actually improved survival over the use of Revlimid and Decadron, in a study conducted by SWOG.

Certainly, that population of patients included some that were possibly transplant-eligible. They were just not meant to be taken to transplant right away. With that piece of information, though, I am more inclined to use a 3-drug regimen if possible, because we have not only a progression-free survival but also an overall survival benefit, albeit with full intensity—Velcade, Revlimid, and Decadron.

The question of whether bortezomib use is difficult in patients who have preexisting neuropathy comes up frequently. In the elderly, it is even more of a relevant factor to take into consideration before deciding therapy. There are patients who have diabetic neuropathy and that, again, can be a contraindication to using bortezomib. The use of bortezomib given subcutaneously these days, and given only once a week, has certainly reduced the intensity and the kind of neuropathy that we used to see in the past. However, by no means has it eliminated it. So, we are trying to avoid—especially in those who have preexisting neuropathy—the use of bortezomib frontline. However, there’s no absolute contraindication that I see in this case to the possible use of bortezomib.

Transcript edited for clarity.

CASE: A 72-year-old Caucasian Man With Relapsed Multiple Myeloma

September 2016

• Patient history: At the age of 72, a Caucasian man was diagnosed with multiple myeloma; R-ISS stage I
• Other relevant history includes hypertension and difficulty walking up stairs
• He was treated with lenalidomide/dexamethasone and achieved a VGPR
• Treatment duration was 9 months; patient subsequently discontinued therapy 12 months ago

June 2018

• On routine follow-up, patient complains of increasing problems with fatigue, and has rising levels of M protein
• Laboratory results:
  • Hb, 9.6 g/dL
  • Ca²⁺9.2 mg/dL
  • Creatinine, 0.8 mg/dL
  • M-protein, 3.0 g/dL
  • 30% plasma cells in bone marrow
• Cytogenetics/FISH: del(17p)
• ECOG PS: 2