Personal Approaches to Discontinuation of Therapy in MM

Ajai Chari, MD, PhD:In terms of the reason to discontinue, the US study, the CALGB, treated patients with LEN [lenalidomide] maintenance till progression. Often in Europe, the duration of maintenance is shorter, anywhere up to 2 years, some of that perhaps being economically driven. But it’s important to remember that the US study did show an overall survival [OS] benefit with the use of continuous lenalidomide. The French study did not, although the nuances are also, it’s important to remember that when we’re looking for overall survival as an endpoint, it’s confounded by salvage therapies and access to salvage treatment. So if in Europe they didn’t have access to adequate salvage, and for example, a lot of the patients in that study who progressed on LEN maintenance got more IMiDs [immunomodulatory drugs]. Whereas in the US [United States], a lot of the patients who progressed on LEN maintenance went on to get PIs [proteasome inhibitors]. And so that makes more sense. If you’re going to not use an appropriate salvage, you will lose the PFS [progression-free survival] benefit in terms of transitioning to an OS.

So I think those are some of the factors to consider. But in the US, typically we would do it till progression. However, we also have to keep in mind that these are human beings, and everybody tolerates these drugs differently. Some patients really get fatigue from lenalidomide or they develop rash, or they have diarrhea, for which we found a good use of Welchol, which a bile sequestrant. And rashes we’ve been also able to manage with re-sensitization.

We published inLeukemia & Lymphomathat if you rechallenge patients with 3 times a week and add steroids and antihistamines, you can gradually desensitize and then omit those supportive care meds [medications]. So there are ways to deal with those [adverse] effects, but I think probably the hardest for some patients was the fatigue.

Studies have shown though that the quality of life in these patients has not been any different in the control arms. But as in an individual patient there’s always a difference. And if a patient chooses to take a break, certainly that’s reasonable, especially, I think the 1 other data point that we now have is the use of minimal residual disease [MRD].

We have this technology now that’s able to detect as few as 1 in 10 to the minus 6^th, or a million cells, and that has been shown to be quite important because patients who attain MRD negativity have prolonged PFS and OS benefits. So in a patient who’s standard risk, who is perhaps…having some difficulty tolerating the therapy, and if they’re MRD negative, it may be prudent actually to give that patient a break. But for the typical patient, and definitely for high risk, I would not stop therapy.

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)