Case Review: Standard-Risk Multiple Myeloma

Ajai Chari, MD, PhD:This is a standard-risk myeloma patient, 53 years old, who gets induction therapy with bortezomib, lenalidomide, and dexamethasone, and after 4 cycles has stem cell transplant consolidation. Importantly he has revised ISS [International Staging System] stage I, so no known high-risk molecular features, nor elevated LDH [lactate dehydrogenase], nor elevated beta-2, so that’s favorable. And after transplant he goes on lenalidomide maintenance.

So this is a pretty typical patient who, based on the SWOG [Southwest Oncology Group] study that showed VRd [bortezomib/lenalidomide/dexamethasone] is superior to Rd [lenalidomide/dexamethasone], triplet induction is pretty standard. And transplant consolidation based on the IFM data shows that that does lead to increased PFS [progression-free survival]. And based on 2 studies, LEN [lenalidomide] maintenance also improves progression-free survival. So this would be standard evidence-based management of a standard-risk myeloma.

The patient did take lenalidomide maintenance for 2 years but apparently was discontinued, and it looks like approximately a year later the patient had a biochemical relapse. There was no evidence of hypercalcemia, renal insufficiency; imaging showed no new bone disease. However, the M [monoclonal] spike was progressively increasing, and the patient was treated with ixazomib, lenalidomide, and dexamethasone.

While the SWOG study showed that bortezomib, LEN [lenalidomide] and DEX [dexamethasone] was superior to LEN/DEX [lenalidomide/dexamethasone], ie, triplets are better than doublets, which I think is pretty well understood in practice, the questions that are being asked now are, should carfilzomib, the more potent proteasome inhibitor [PI], be used in frontline therapy? Basically the ENDEAVOR study compared carfilzomib at 56 mg per meter squared to bortezomib twice weekly and showed superior PFS and OS [overall survival].

However, it’s important to note that that was only the PI and DEX [dexamethasone]. When we added an IMID [immunomodulatory drug], it’s not recommended to give more than 36 mg per meter squared. So it’s not clear what the additional value-add of carfilzomib in frontline therapy would be at a lower dose. That said, many people would do that, and that is something to consider in a high-risk patient or in a patient with neuropathy; in a young patient. Probably wouldn’t do that in a patient with known cardiac history, but the risk of cardiac events is quite low.

The other work being done in induction therapy right now is quadruplet. And the GRIFFIN study was just presented at this year’s [2018] ASH [American Society of Hematology annual meeting], although it was primarily the safety, and this is VRd [bortezomib, lenalidomide, dexamethasone] with daratumumab in a frontline [regimen]. And the results were quite impressive. Although we only had 16 patients, it was more of a safety run-in, and the response rate was 100%, CR [complete response] rate 63%. So those are very encouraging data, and I think it will beg the question of, what is the role of transplant if we use quadruplet induction? Obviously, that data are still a while away, but in 2019, and probably very soon in 2019 and possibly 2020, I suspect quadruplet induction will be more de rigueur.

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)