The more the merrier in newly diagnosed multiple myeloma

Blood cancers

10 Apr 2019

In the first of two talks at Amgen One Multiple Myeloma stream, Associate Professor Hang Quach introduced the “Queen of multiple myeloma in the States,” Professor Noopur Raje from Harvard Medical School to discuss her standard approach to managing newly diagnosed multiple myeloma. During her talk, she sympathised with the challenges Australian clinicians face and gave her opinion on what she would do in a similarly restrictive reimbursement state.

“In the States we are lucky to have a lot of resources available. Triplets, including Immunomodulatory imide drugs (IMiDs) are standard practice followed by transplant and maintenance therapy.1-4 Rather than treat patients individually, I tend to treat everyone the same – whether they are high risk or not. My philosophy is that we have these powerful treatments available, so why not treat the standard risk patient as aggressively as I would a high risk one?” began Prof. Raje.

Jury’s still out on what MRD negativity really means in practice

“Now that we are seeing such deep responses, and often rapidly, the next question is should MRD [minimal residual disease] negativity be the goal? The problem is that even MRD negative patients relapse,1,3,5-10noted Prof. Raje.

So here’s what we know and what we don’t,” summarised Prof. Raje. “MRD remains a research tool, but indications are that lower levels of MRD predict for better outcomes which helps to define response and monitor efficacy of therapy. While it’s the best and most easily exportable method available, the optimal time point is still under investigation. How soon is too soon to make a call on MRD negativity – one month, one year, two years – we still don’t know,” she explained. She said that a sobering reminder for the audience was that as exciting as MRD negativity has been, patients still relapse and we don’t yet know whether changing therapy based on depth of response alters survival outcomes.

Prediction: transplant is still in, but could be on the way out at some point in the future

Taking the audience through the latest trials in the newly diagnosed MM space, Professor Raje paused on a question around the role of transplant in the future. “Transplant eligibility has changed and is less about age and more about fitness. What’s more, studies like FORTE are begging the question as to whether patients will need a transplant if their response is deep enough after induction therapy,”11 she remarked. However, while trials like FORTE are examining induction therapy, the vast majority of trials are still focussed on the maintenance phase of therapy in transplant-eligible patients.

One size should fit all

Professor Raje reiterated that her approach is to treat every patient as if they were a high-risk one. “We see survival in certain patient groups (like the elderly) is inferior to younger patients. I think this is possibly due to less frequent use of newer and more effective agents in these patients.12 For me, I don’t waste time tinkering, I want to give most potent therapy the patient can handle to give them the best chance I can,” she said. “In frail patients, rather than changing the therapy we’re looking at lite regimens, which are showing promising results not only for clinical parameters, but patient health-related quality of life as well.”12 This last point was one of the three questions Prof. Raje left the audience with:

  1. Can we aim for MRD negativity (more specifically how do we do that)?
  2. Can we test fixed-duration therapy with 4-drug combinations in the future led by MRD endpoints?
  3. How can we incorporate health-related quality of life studies (particularly as we get patients living longer)?

 

This article was sponsored by Amgen, which has no control over editorial content. The content is entirely independent and based on published studies and experts’ opinions, the views expressed are not necessarily those of Amgen.

References:

  1. Richardson PG. et al. Blood 2010;116(5):679-686.
  2. Durie BGM, et al, Lancet 2017;389(10068):519-527.
  3. Jakubowiak AJ, et al. Blood 2012;120(9):1801-1809.
  4. Attal M, et al. N Engl J Med 2017;376:1311-1320.
  5. Rajkumar SV, et al. Lancet Oncol 2010;11(1):29-37.
  6. Morgan GJ, et al. Haematologica 2012 ;97 :442-450.
  7. Harousseau J-L, et al. J Clin Oncol. 2010;28:4621-4629.
  8. Cavo M, et al. Lancet 2010;376:2075-2085.
  9. Bringhen S, et al. Blood 2014;124(1):63-70.
  10. Gay F, et al. J Clin Oncol 2017;35(Suppl15):8003.
  11. Schaapveld M, et al. Eur J Can 2010;46(1):160-169.
  12. O’Donnell EK, et al. Br J Haematol 2018;182(2):222-230.

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