Impressions of an Elderly Male With R/R Multiple Myeloma

Ravi Vij, MD, MBA:We have a 75-year-old gentleman who was diagnosed with multiple myeloma. He originally got treatment with lenalidomide and dexamethasone for about 9 months and then, due to his own preference, stopped therapy. Generally, these days we try to give therapy until progression. But in this case, the gentleman desired to stop treatment. The good thing is that he had a very good partial response, and he after that went a number of years without any need for therapy. He once again started showing evidence of some fatigue and some constitutional symptoms. Thereafter, a workup showed that his disease was starting to progress with some mild anemia and back pain, with new compression fractures. So this is a situation where we know that a patient is going to probably require treatment. He underwent a bone marrow biopsy again, and as expected demonstrated a number of plasma cells in excess of normal. Therefore, he also had chromosomal testing done, and that showed that he had this adverse 17p deletion abnormality.

The treatment for multiple myeloma has certainly evolved, both for the transplant-eligible and for the transplant-ineligible patients. For transplant-ineligible patients, we’ve certainly come a long way from the era when we used to give these patients melphalan and prednisone. We went through a period where people tried to improve upon the melphalan/prednisone standard by adding a third drug. Melphalan/prednisone/thalidomide, melphalan/prednisone/Revlimid, and melphalan/prednisone/Velcade have all shown benefit over melphalan and prednisone. But it was always felt that melphalan was a drug that if we could do away with it, would be best, given its unpredictable response, somewhat delayed response, and its toxicity.

The trial that was done a few years ago was called the FIRST trial, where lenalidomide and dexamethasone was compared to a standard of melphalan/prednisone/thalidomide, and continuous therapy with lenalidomide and dexamethasone until progression proved to be superior. It led to a new standard being established for transplant-ineligible patients. Since that time, there have certainly been other studies that have been done and reported on. We know that in patients who are named transplant-ineligible but are still in reasonably good shape for treatment, often we will give them a 3-drug regimen. One of the more popular ones is the 3-drug regimen of bortezomib with lenalidomide and dexamethasone [VRd].

The fact is, the 3-drug regimen at full intensity often is not well tolerated by an elderly population, so the regimen that we call VRd-lite has become popular. You end up giving the Velcade once a week instead of twice a week, the lenalidomide at a lower dose, as the dexamethasone. For patients who are between 70 and 80 years of age, that has become a popular regimen in recent years. For people who are octogenarians, for whom we are a little hesitant to give 3 drugs, lenalidomide and dexamethasone is still a standard that people accept.

Now, more recently, we’ve had data emerge from a new generation of trials looking at monoclonal antibodies in frontline therapy. In that regard, daratumumab with melphalan, Velcade, and Decadron was shown to be superior to the FDA-approved standard of Velcade with melphalan and prednisone. And what we now know is that it is the first quad, as we call it, the first 4-drug regimen that we have FDA approved for myeloma. There has been some hesitancy in adopting that widely, given that there is melphalan in the mix, and people have wanted to move away from melphalan. We also know from the American Society of Hematology meeting in December 2018, we had a presentation that showed that the 3-drug regimen of daratumumab with Revlimid and Decadron was superior to the 2-drug regimen of Revlimid and Decadron. So I think that once that gets approved by the FDA in the future, that will become a very popular regimen for the transplant-ineligible patient population.

There are a number of other trials ongoing that will also be reported on in the near future that are eagerly awaited. These include trials looking at ixazomib with lenalidomide and dexamethasone compared to lenalidomide and dexamethasone, and a trial of elotuzumab with lenalidomide and dexamethasone, again compared to lenalidomide and dexamethasone. How these fit into the landscape, once these trials hopefully are positive and lead to the approval of these drugs, remains to be seen.

Transcript edited for clarity.

Case: 75-Year-Old Man With Symptomatic R/R Multiple Myeloma

January 2015

• A 75-year-old man was diagnosed with multiple myeloma; R-ISS stage I
• PMH: hypertension; coronary artery disease post stent placement
• Patient was treated with lenalidomide + dexamethasone for 9 months; transplant-ineligible due to age and performance status
• Patient achieved a VGPR, discontinued treatment thereafter due to patient request

September 2018

• On routine follow-up 3 years later, patient presents with new-onset back pain and generalized fatigue
• Imaging: multiple new lytic lesions with compression fractures
• Laboratory results:
  • Hb, 10.7 g/dL
  • Ca²⁺, 9.3 mg/dL
  • Creatinine, 1.1 mg/dL
  • M-protein, 3.2 g/dL
• Cytogenetics/FISH: del (17p) discovered at relapse
• ECOG PS: 2