Convenience of Oral Regimen for the Treatment of MM

Robert A. Vescio, MD:I’ve used IRd—ixazomib, lenalidomide, and dexamethasone—pretty frequently, partially because of its convenience. Again, I probably work at the hardest institution to drive to in the country, and patients do live far away, and so drugs administered in the cancer center are challenging. I’ve had reasonable success with triplet therapy, particularly to keep people in remission when they did well with bortezomib, lenalidomide, and dexamethasone. There are patient-tolerability differences. Some patients get gastrointestinal side effects from ixazomib, and that seems to be dose dependent. In my own experience, it seems like many patients don’t tolerate the full-formula dose. I have to lower it to 3 mg or even 2.3 mg. The drug has a long half-life—over a week—and so it tends to build up over time. Patients will typically tell you that if they’re having fatigue or gastrointestinal side effects from the drug, the third week is harder than the first week. That’s how you can pinpoint that ixazomib is causing the problem, and then you can just dose adjust.

For some patients, convenience is important. And so, having an all-oral regimen available allows patients to continue on with their life and not be stuck going to cancer centers for treatment—either infusions or shots—somewhat indefinitely. It’s a pill. It’s easier to just continue with the regimen that worked for them as part of their initial therapy. So, I think it may be a way of keeping people’s disease controlled for a longer period of time, right from the very beginning.

Also, the drug can be given closer to its maximal dose or can be given at its maximal dose because patients are willing to take a pill. Often, in the beginning, similar proteasome inhibitors are used at their more maximal dose and then get tapered down with time because of patient preference. That’s where ixazomib has a role. To be truthful, with carfilzomib, if somebody is sick and you need a quick response, this option tends to work more quickly and aggressively. I would use that drug in those types of patients, but ixazomib has the advantage of convenience.

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