Managing High-Risk Multiple Myeloma - Episode 5

Myeloma: The ALCYONE Trial

C. Ola Landgren, MD:We discussed previously that the field has come to a point where 3-drug combinations are considered to be the standard of care for the treatment of newly diagnosed patients with myeloma. The same is true for patients who have relapsed disease. All of the studies show that 3 drugs are better than 2 drugs. So, 3 drugs are really the new standard of care.

The question on the table is, is 3 really enough? Should we think of 4 drugs? There are not very many studies using modern therapies that have addressed this question. The first study to do that was published in early 2018, the ALCYONE study, in theNew England Journal of Medicine. It’s a hybrid of daratumumab, or Darzalex, the CD38-naked antibody drug, which is one of the newest drugs in combination with really very old drugs—melphalan and prednisone. Have to go back all the way to the 1950s. And it’s also in combination with bortezomib, which is the first cortisone inhibitor that was developed in myeloma and FDA approved in 2003.

This study used all of those 4 drugs—daratumumab, melphalan, prednisone, and bortezomib (Velcade), the 4-drug combination—in the experimental arm, and the control arm used the 3 drugs—melphalan and prednisone with bortezomib. So, daratumumab was not given in the control arm. This study was presented at an oral presentation at the American Society of Hematology meeting, ASH, in 2017 in Atlanta before it was subsequently published in theNew England Journal of Medicine. So, these results, as indicated by the prominent journal and the oral presentation at the meeting, were considered to be striking.

The study showed that you had a benefit in progression-free survival. It should be said that the use of melphalan/prednisone/bortezomib is not really a combination that’s used in the United States. Melphalan and prednisone, I think, have almost been banned the past 10 years. And this is because of the development of so many new medications that are available. It’s still used in other countries. It’s used commonly in Asia, Europe, and elsewhere.

So, I think the combination in the study is probably not of major interest for treating physicians in the United States. But it is an interesting study, I think, for a couple of reasons. One is that it shows that the 4-drug combination could be a way to go, and there are many new 4-drug combinations in development with more active, more modern drugs. Also, it shows that the daratumumab drug can be used up front, and that’s a new piece of information that I think is very important.

And the last thing that I think is important is that the drugs that daratumumab was partnered with, the older drugs, are not that efficacious. Still, this study showed that you could obtain minimal residual disease-negativity rates in the range of about 20% to 25% in patients treated with these 4 drugs. So, I think these are important and interesting pieces that the study delivered.

Transcript edited for clarity.

  • A 74-year-old woman presented with anemia, proteinuria, renal insufficiency, and pain in her right hip
  • History: chronic HTN, aortic insufficiency, diabetes mellitus
  • ECOG performance status, 1
  • X-Ray of the pelvis showed numerous lytic lesions in the ilium and a large lesion in the right proximal femur
  • MRI confirmed a 9-mm lesion in the right femoral head and numerous bilateral T1 hypointense and T2 hyperintense lesions in both iliac region
  • Laboratory results:
    • Hb, 10.1 g/dL
    • Ca2+3.32 mmol/L
    • Creatinine, 1.9 mg/dL
    • Creatinine clearance, 30 mL/min
    • M-protein, 1.4 g/dL
    • B2M, 4.9 mcg/mL
    • SFLC, kappa, 150 mg/dL
  • Bone marrow biopsy, 70% plasma cells
  • Molecular testing, del17p