Caring for Patients on IRd Therapy in R/R Multiple Myeloma

Ravi Vij, MD, MBA:The TOURMALINE-MM1 study looked at patients who had relapsed after 1 or more lines of treatment. These patients were randomized to either the 3-drug oral regimen of ixazomib, lenalidomide, and dexamethasone or the prevailing standard at that time of lenalidomide and dexamethasone. The study showed a statistically significant improvement in progression-free survival, which was the primary endpoint of this study. It also showed that patients had deeper responses when ixazomib was added to the 2-drug regimen. The toxicity profile of the 3-drug regimen did not seem to be too different compared to the 2-drug regimen. Also, in the study it was found that high-risk cytogenetic patients, even those with a 17p deletion, seemed to benefit with the addition of ixazomib to lenalidomide and dexamethasone. So this FDA-approved regimen offers a potential convenient effective therapy for a lot of our patients.

The patient that we are talking about today is an older gentleman who has performance status of 2. This gentleman is in need of treatment, and I think that the regimen of ixazomib, lenalidomide, and dexamethasone is very appropriate for a patient of this nature because of the convenience that the regimen offers. It is a regimen that the patient can take at home. The regimen is well tolerated by older individuals. It is a regimen that also, given his 17p deletion, would at least based on the TOURMALINE-MM1 study be effective as well as if he did not have high-risk chromosomal features.

Ixazomib is a drug that I think is appropriate for patients who are older, especially for those who have a limited performance status. The drug’s toxicities are relatively mild and the drug is well tolerated. In somewhat frailer patients, one of the things we often try to balance with efficacy is the lack of toxicity. Ixazomib can cause, in some patients, fatigue, but usually it is not too marked. It also in some cases causes the patients to develop a mild neuropathy or a rash, but those are also, in my own experience, not major issues. So, in older patients, I think this drug regimen is well tolerated.

The use of ixazomib also offers older patients an all oral regimen in combination with lenalidomide and dexamethasone. These patients often have issues coming to the doctor’s office, so taking a pill at home once a week together with the lenalidomide and dexamethasone offers them the convenience of home administration of the drugs. It is also less disruptive often to the caregivers. They don’t have to take off work to bring their loved ones to the doctor’s office either. So I think that the 3-drug regimen of ixazomib, lenalidomide, and dexamethasone has advantages that certainly, for a patient who is older and somewhat frailer, go beyond just the patient description and the demographic to extend to his caregivers and those around him.

Patients with multiple myeloma certainly need to have supportive care measures. The one thing patients with myeloma need is something to preserve their bone strength. The use of drugs like bisphosphonates or RANK ligand inhibitors have been shown to improve the quality of life for patients. Patients who get proteasome inhibitors have a higher chance of developing zoster infections, so we should be sure about putting patients on antivirals. For those getting immunomodulatory drugs, especially in combination, we need to be heightened to the possibility of them developing deep venous thrombosis. We need to have these patients on the appropriate strategy to reduce the risk for blood clots. In most cases, the use of aspirin is thought to be adequate. But people who have had prior problems with blood clots are at a higher risk for blood clots than the average patient, and full anticoagulation is often necessary.

Transcript edited for clarity.

Case: 75-Year-Old Man With Symptomatic R/R Multiple Myeloma

January 2015

• A 75-year-old man was diagnosed with multiple myeloma; R-ISS stage I
• PMH: hypertension; coronary artery disease post stent placement
• Patient was treated with lenalidomide + dexamethasone for 9 months; transplant-ineligible due to age and performance status
• Patient achieved a VGPR, discontinued treatment thereafter due to patient request

September 2018

• On routine follow-up 3 years later, patient presents with new-onset back pain and generalized fatigue
• Imaging: multiple new lytic lesions with compression fractures
• Laboratory results:
  • Hb, 10.7 g/dL
  • Ca²⁺, 9.3 mg/dL
  • Creatinine, 1.1 mg/dL
  • M-protein, 3.2 g/dL
• Cytogenetics/FISH: del (17p) discovered at relapse
• ECOG PS: 2