Maintenance Therapy Outcomes in Multiple Myeloma

Ravi Vij, MD:Those on maintenance therapy in transplant-eligible patients have been the subject of several trials. The use of maintenance or continuous therapy is, I think, the standard of care that has emerged over the last several years in the treatment of multiple myeloma. This is based on prospective trials that have looked at shorter courses of treatment versus prolonged courses of treatment. That is something that was actually part of the study with the FIRST trial, wherein the regimen was looked at in a 3-arm study in which 1 arm received lenalidomide (Revlimid) and dexamethasone for a finite period of time, and the other arm received lenalidomide and dexamethasone followed by lenalidomide until progression. The primary analysis showed that the arm that received lenalidomide to progression proved to be superior to the control arm.

So, I think that certainly, if possible, our goal is to give every patient who walks in our door these days some form of continuous therapy. Having said that, in patients who are on lenalidomide maintenance, there are issues that sometimes emerge with cytopenia. There are issues that emerge with prolonged lenalidomide use that bordered on neuropathy. Some have gastrointestinal intolerance; others actually complain of profound fatigue. So, especially in the elderly, balancing the quality of life with the long-term benefits of a drug may sometimes require us to stop the treatment in patients before they progress. Even in the transplant-eligible patients, actually a proportion of patients cannot tolerate the drug long-term.

Regarding the choice of maintenance therapy, the best data that exists is with the use of lenalidomide. However, there are trials that are ongoing, looking at ixazomib (Ninlaro) as maintenance therapy and also a monoclonal antibody as long-term maintenance, which may drive our use of alternative maintenance strategies in the future.

This patient had his therapy discontinued after 9 months. We are not provided with much data on why this was done, whether this was because the patient could not tolerate the drug, whether this patient wanted to stop the drug, or whether the physician himself thought that with a very good partial response, it was no longer necessary to continue treatment.

Certainly, if it were the patient wanting to discontinue treatment, or there were side effects, I think stopping the treatment is absolutely appropriate, especially in the elderly. However, if possible, we should try to continue treatment on patients long term, until time of disease progression, because the data from randomized trials suggest that strategy is what seems to be the best, especially with the use of lenalidomide and dexamethasone. We also have data from a meta-analysis, published by Dr. Anthony Palumbo in theJournal of Clinical Oncologya few years ago, that looked at trials in which patients were either given continuous therapy or alternatively, got a finite period of therapy and then restarted therapy at progression. This meta-analysis showed that the use of continuous therapy led to superior outcomes in terms of not only time to next treatment, PFS1, but also PFS2 and overall survival, and were better when you tended to continue therapy long term.

Transcript edited for clarity.

CASE: A 72-year-old Caucasian Man With Relapsed Multiple Myeloma

September 2016

• Patient history: At the age of 72, a Caucasian man was diagnosed with multiple myeloma; R-ISS stage I
• Other relevant history includes hypertension and difficulty walking up stairs
• He was treated with lenalidomide/dexamethasone and achieved a VGPR
• Treatment duration was 9 months; patient subsequently discontinued therapy 12 months ago

June 2018

• On routine follow-up, patient complains of increasing problems with fatigue, and has rising levels of M protein
• Laboratory results:
  • Hb, 9.6 g/dL
  • Ca²⁺9.2 mg/dL
  • Creatinine, 0.8 mg/dL
  • M-protein, 3.0 g/dL
  • 30% plasma cells in bone marrow
• Cytogenetics/FISH: del(17p)
• ECOG PS: 2