A 68-Year-Old Man with Multiple Myeloma - Episode 5

Clinical Pearls for the Management of MM

An expert in multiple myeloma provides clinical pearls for disease management from initial diagnosis through multiple lines of therapy.

Natalie S. Callander, MD: What is important for people who are seeing patients with myeloma, perhaps that’s not your primary focus of your practice, but you’re seeing them here and there, is we want to emphasize a couple of things. One is, when those patients first come in the door, we want you to try to use effective therapy right up front, to give those patients the longest duration of response. That can be for a transplant-eligible patient considering a triplet or maybe a quadruplet regimen in patients with high risk. And we do think autologous stem cell transplant still adds in terms of progression-free survival [PFS] and probably depth of response. Then we think that patients deserve some sort of maintenance, whether it’s going to remain 1 drug, such as lenalidomide or bortezomib. There’s a very large trial underway that’s going to add in daratumumab as a possibility for maintenance, but we want to try to take a very good swing. 

For nontransplant eligible patients, there are several good choices. Daratumumab in combination with lenalidomide and dexamethasone as tested in the MAIA trial looks very promising. There is great now 6-year follow-up showing they had not even reached their PFS at that point, but it’s probably going to be at 5 to 6 years. Or the combination of bortezomib, lenalidomide, and dexamethasone. Some people call that VRd [bortezomib, lenalidomide, dexamethasone]-lite, if you’re trimming the doses a little, making the bortezomib weekly. Those are very good introductory choices for patients.

In terms of the relapsed setting, this is where it gets a little trickier. We would all agree, for patients who have a relapse that symptomatic triple therapy is great. We would like to figure out by future trials whether you need to change all the classes or only 1. That is an important question. Again, the NCCN [National Cancer Comprehensive Network] guidelines have a number of different options. I would always encourage somebody to think about a clinical trial for patients too. Where it starts to get a little harder is that third- and fourth-line therapy, and again, there are a number of good choices. We tend to look in the third and fourth line at what kind of [adverse] effects the patients may be experiencing at that point. What kind of cytopenia maybe they’re experiencing; do they have a lot of peripheral neuropathy? What’s their distance from the treatment location? Those kinds of considerations can be important in making a decision for relapsed therapy. I do think CAR [chimeric antigen receptor] T-cell transplant is going to be an option for you to refer patients to. We’re going to have a couple of different CAR T products approved this year, we believe. 

Finally, quality of life and supportive care are important. In this day and age, with COVID-19, we are advocating vaccination for patients, but we don’t want to forget about some of the common things too, such as influenza and pneumococcus. We are recommending COVID-19 vaccinations for our patients. Typically, right now expert opinion is recommending consideration of COVID-19 vaccination 90 days after a transplant, and many of us are trying to vaccinate patients perhaps in a 1- or 2-week hiatus between some of their dosing schedules. In addition, we want to make sure we think about bone health, so we’ve got 2 excellent options, zoledronic acid and denosumab. We also have pamidronate, which can be useful in some situations as well. We also know that patients can experience increased risk of infection in their first few months after diagnosis, and so this is a vulnerable period where we think there should be a lot of vigilance, and in some cases antibiotic prophylaxis can be helpful.

For nontransplant patients, we have a couple of very good choices. The MAIA trial was recently updated at ASH 2020 [the American Society of Hematology annual meeting]. One of the exciting things, using a combination of daratumumab, lenalidomide, and dexamethasone, they presented that even after an average of 48 months of follow-up they still hadn’t reached the progression-free survival median in the daratumumab-containing arm. The projected median PFS is going to be about 5 or 6 years on that trial for that particular arm; so those are really great data. Another choice for transplant-ineligible newly diagnosed patients would be a combination such as bortezomib, dexamethasone, and lenalidomide, particularly with weekly bortezomib, what we would call VRd-lite. And then the TOURMALINE trial using a combination of ixazomib, lenalidomide, and dexamethasone would also be a very reasonable choice for patients who are transplant-ineligible, and particularly those who are looking for a regimen that can be done orally and not require lots of visits to the center.

This transcript is edited for clarity.

A 68-Year-Old Man with Multiple Myeloma

Initial Presentation

  • An active 68-year-old man presented with a 5-month history of fatigue and new onset hip pain
  • PMH: HTN, medically controlled
  • PE: tenderness appreciated on palpation at the hips and lower back
  • ECOG PS 1


Clinical workup

  • Labs: Hb 10.3 g/dL, calcium 11.4 mg/dL, LDH 190 U/L, creatinine 1.2 mg/dL, albumin 3.9 g/dL, beta-2 microgloblulin 3.9 mcg/mL, M-protein 2.7 g/dL, lambda free light chains 4.1 mg/dL, CLCr 45mL/min 
  • Hepatitis B and C negative
  • Skeletal survey showed lytic lesions in the left hip 
  • Bone marrow shows 42% clonal plasma cells IgG k
  • FISH: del(17p)
  • Diagnosis: R-ISS stage II MM

Treatment

  • Initiated lenalidomide + bortezomib + dexamethasone for 8 cycles
  • He underwent ASCT 
  • He continued 15 months maintenance lenalidomide
  • Imaging at follow-up revealed progression of disease 
  • Selinexor + bortezomib + dexamethasone was initiated