Real-World Advice for IRd Triplet in Relapsed MM

Ajai Chari, MD, PhD:If somebody’s using ixazomib/LEN [lenalidomide]/DEX [dexamethasone] [IRd] for the first time, I would say the things to think about are the dosing of ixazomib is 4 mg once weekly—3 weeks on, 1 week off. So day 1, 8, and 15. It is important to adjust the dose of ixazomib if somebody has impaired renal function. We did the pharmacokinetics study at [Icahn School of Medicine at] Mount Sinai, which showed that patients who have impaired renal function with clearance less than 30 [mL/min] do accumulate the drug at higher levels. So for those patients the Ninlaro, or ixazomib, should be reduced 3 mg.

As with all proteasome inhibitors [PIs], zoster prophylaxis is required. We have seen recent data that the new Shingrix vaccine, which has killed, has been shown to be safe in myeloma patients. In terms of its benefits we don’t know yet, we don’t have long-term data. But I think in this patient population if you’re going to be using a PI, regardless of vaccination status, patients should still be getting shingles prophylaxis. And of course because of the use of lenalidomide and with dexamethasone, the thrombotic prophylaxis is equally important, typically aspirin daily. If somebody has a history of thrombotic events or is high-risk because of immobilization, surgery, airline flights [then] therapeutic anticoagulation with enoxaparin or Xarelto, the like, would be advised.

The one thing I think I would do in personal practice that is not technically on label from the study is if you ask patients what’s their least favorite drug, it’s dexamethasone. And so we do this IRd regimen per protocol, which is 40 mg a week of DEX [dexamethasone]. But if you’ve debulked the patient and you really now are just trying to maintain their remission, do you really need to get your patient not sleeping every day, gaining weight, being irritable? I think it’s very reasonable to taper the DEX [dexamethasone] off and just maintain patients on ixazomib and LEN [lenalidomide] to allow them a better quality of life and the adverse effects of steroids.

So in summary we saw here a standard-risk myeloma patient who got induction, transplant, maintenance and then relapsed off maintenance about a year after lenalidomide and got ixazomib/LEN [lenalidomide]/DEX [dexamethasone] for relapsed myeloma. He had a biochemical relapse. So I think this case highlights a lot of the considerations. We discussed the importance of looking at patient factors, disease factors, and treatment factors. It’s nice to have so many choices in treating relapsed myeloma. And so when we consider those factors, there will never be one right regimen for all patients. And in a patient who’s looking for a completely oral regimen that’s efficacious, that can be given because of a convenience till progression, IRd is a great option.

Transcript edited for clarity.

Case: 56-Year-Old Man With Asymptomatic Relapsed Multiple Myeloma

History:

• In 2015, at the age of 53, an African-American man was diagnosed with multiple myeloma; R-ISS stage I
• Patient was treated with bortezomib + lenalidomide + dexamethasone (VRd) for 4 cycles, followed by ASCT
• Patient achieved a VGPR
• Received lenalidomide maintenance for 2 years

September 2018

• On routine follow-up, no clinical symptoms observed
• Imaging: stable disease
• Laboratory results:
  • Hb, 11.3 g/dL
  • Ca²⁺9.2 mg/dL
  • Creatinine, 0.8 mg/dL
  • M-protein:
    • June: 1.2 g/dL
    • July: 1.4 g/dL
    • August: 1.7 g/dL
• Cytogenetics/FISH: no adverse cytogenetics
• ECOG PS: 0
• Patient was started on ixazomib + lenalidomide + dexamethasone (IRd)