Future Treatment Landscape for RRMM

Multiple myeloma expert, Dr Clifton Mo, shares his insights on future directions for the treatment of multiple myeloma.

Clifton C. Mo, MD: I hope to see myeloma turn from an incurable disease to a curable disease, and we are certainly working on that. I’m hopeful that we can get there. However, until we are there, we are dealing with an unfortunately incurable hematologic malignancy, but it is now highly treatable. It is increasingly treatable with an increasing number and increasing quality of therapeutic options from which to choose. In that sense, it’s important to think of myeloma treatment as a marathon and not a sprint, and to try to think about things in terms of strategy and not just tactics.

We are ultimately interested in winning the war and not just the first battle. We’re looking for maximizing longevity but also maximizing quality of life and helping people feel better because of their treatment as opposed to feeling worse. All of these things need to factor in at every step of the way in terms of decisions that are being made for patients who are newly diagnosed, as well as those who’ve received 1 line or 5 lines of therapy.

As we get more experienced with our newer agents, we’ll have a better understanding of how to tailor these treatment regimens individually to our patients based on their personal disease characteristics and their medical comorbidities or lack thereof, as well as, importantly, the personal preference of the patient, what their goals are, and what they’re most and least comfortable with in terms of risks and adverse effects. I see the overall horizon continuing to brighten in terms of the myeloma treatment landscape. I see things becoming less of a cookie-cutter, one-size-fits-all, oncology-by-numbers approach and more of an individualized therapeutic approach to each individual patient, with an increasing number of options as well as gray areas and treatment dilemmas.

Overall, the problems that we now have in multiple myeloma in terms of choosing 1 drug or 1 regimen over another are great problems to have, and they’re all reflective of the fact that things are getting better: our treatments are getting better, and our patients are continuing to live longer. Certainly, with all the work that we [at the Dana-Farber Cancer Institute] and our colleagues across the country and around the world are doing, that’s only going to continue to improve.

My advice for community oncologists referring patients with myeloma is that, first of all, clinical trial options for therapy should be strongly considered in general, perhaps especially for patients with relapsed/refractory disease, when such a therapeutic option is feasible from a logistical or geographic standpoint. The next thing I’ll say is that these treatments are becoming increasingly difficult as the therapeutic options continue to increase in number. I think that consultation with a multiple myeloma specialist is probably a good thing to consider to allow for some degree of comanagement, for lack of a better term. This can be somebody periodically throwing their 2 cents in to try to figure out the best individualized approach for each patient.

Lastly, it’s important to consider not only the efficacy data from clinical trials and the end points we always hear about in terms of CR [complete response], MRD [minimal residual disease], and things like that, which are certainly important things to look at in our clinical trials when evaluating the value of different drugs and regimens. However, on a practical basis, the patient-specific factors are arguably just as important if not more important to consider when trying to find the best regimen at every step along the way for an individual patient because we now have multiple drugs within our major classes of myeloma therapy. We have an increasing number of classes of drugs that have been recently FDA approved, so when we have so many more options from which to choose, it’s important to think of tolerability as well as risk of potential complications as being just as important as CR or MRD negativity when choosing a regimen for a patient in the real world.

By no means is it an easy decision in 2021, and by no means is it going to get easier. It’s going to get more difficult, but the important point to remember is that, even though it’s more difficult for us, it’s reflective of the fact that things are getting better and better for our patients, which is a great thing.

Transcript edited for clarity.

Case: A 79-Year-Old Woman with Multiple Myeloma

Initial Presentation

  • A 79-year-old woman presented with intermittent nausea, decreased appetite and tingling and numbness in her feet bilaterally
  • PMH: HTN, medically controlled
  • PE: thin, tired appearing woman, otherwise unremarkable; grade I peripheral neuropathy
  • ECOG PS 0

Clinical Workup

  • Labs: Hb 9.6 g/dL, calcium 10.5 mg/dL, LDH 210 U/L, creatinine 1.1 mg/dL, albumin 3.8 g/dL, beta-2 microglobulin 3.2 mcg/mL, M-protein 2.9 g/dL, serum free kappa light chains 4.4 mg/dL, CLCr 35mL/min
  • Hepatitis B and C negative
  • Skeletal survey and MRI showed a lytic lesion in her spine L3/L4
  • Bone marrow shows 45% clonal plasma cells IgG k
  • FISH: hyperdiploid
  • Diagnosis: R-ISS stage I MM


  • Initiated lenalidomide + bortezomib + dexamethasone for 8 cycles + lenalidomide maintenance for 9 months
  • Follow-up at that time revealed disease progression
  • Initiated selinexor + bortezomib + dexamethasone
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