IRd Triplet for Relapsed Multiple Myeloma

Robert A. Vescio, MD:When this patient was first treated for her high-risk disease, she received triplet therapy, and it seemed to work. When she stopped the proteasome inhibitor, her disease ultimately progressed.

When we use 3 drugs, it’s often hard to know which of the 3 drugs is the most important. Sometimes we learn that out later. Again, given her high-risk disease with the t(4;14) translocation, I would generally be in favor of using a proteasome inhibitor, particularly since she was using one that worked initially. So, I would give her the option of going back to bortezomib or ixazomib or, for that matter, Kyprolis (carfilzomib). Again, I think convenience is important to patients, and I’m certainly fine with her using ixazomib as a more simple, effective regimen to start.

The TOURMALINE-MM1 trial compared the use of lenalidomide and dexamethasone to a triplet regimen—ixazomib, lenalidomide, and dexamethasone—as treatment for patients with relapsed multiple myeloma. An improved progression-free survival was seen in the patients who took the ixazomib-containing regimen. The patients were then analyzed based on their risk categories, and there was an advantage in progression-free survival for both the standard-risk patients and the high-risk patients. This kind of backs up the fact that patients with high-risk disease tend to do better with a regimen that includes a proteasome inhibitor, such as ixazomib, versus one without.

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