Second-Line Options in Biochemically Relapsed MM

Ajai Chari, MD, PhD:When we have a patient who’s relapsing, there are a lot of factors to consider. I would probably classify them into patient factors, disease factors, and treatment factors. So if they’re patient factors, we’re talking about age, comorbidities, blood counts, renal function, neuropathy, profession, distance from the cancer center, willingness to take oral versus IV [intravenous], compliance with oral therapy. So a lot of those factors are important. With the disease, we need to think about the biology. Is this a high risk or standard risk? Extramedullary disease, slowly progressive, rapidly progressive, biochemical relapse versus fulminant relapse. Those are a lot of factors. And then in terms of treatment, oral, IV, triplet, doublet, cost, access … and, of course, adverse effects.

And perhaps one of the biggest things we need think about in the relapsed setting that’s not in the newly diagnosed is, what were the patient’s prior therapies? If a patient has been taking a drug till progression, obviously we should eliminate that and move on. If, however, a patient was taking a drug and tolerated it well and had a good response, we could certainly use it again.

So in this particular patient since the lenalidomide was discontinued, presumably due to patient or physician preference, a LEN [lenalidomide]-based regimen could be used in this patient. Unlike somebody who progressed overtly on LEN maintenance. Such patients are important to consider because they often can get excluded from clinical trials with Rd [lenalidomide/dexamethasone]-containing backbones, because obviously if somebody had LEN maintenance progression, their benefit from adding a third drug might not be as good as somebody who’s totally sensitive to LEN.

And then in terms of what we could add, luckily, we have in myeloma a lot of choices and 4 high-impact publications, all of which showed benefit with the addition of a third drug. The studies are ixazomib, in TOURMALINE—that was published inNew England [Journal of Medicine]; daratumumab, elotuzumab, or carfilzomib. So these are the 4 drugs that we can play with. They all have their pros and cons. I think it’s nice to have options because you can accommodate each patient’s unique needs and adverse effect profile. In this particular case ixazomib was chosen. And what’s unique about this one is it’s the only completely oral regimen, and so that’s great for patients, and it’s definitely something to consider in a patient who does not have a fulminant relapse, it’s a biochemical relapse; somebody who may not want to come to the cancer center every day. Perhaps somebody who is young and working and busy, it’s nice to have a completely oral regimen.

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)