MRD, Transplant & Relapsed Treatment at IMW 2017

Welcome to Day 2 of IMW 2017 New Delhi!

Today featured some great sessions on MRD, transplant, treatment of relapsed MM, and supportive care and side effect management. A quick summary is below, followed detailed notes for those who want deeper, more specific information on any of the topics:

Treatment for Relapsed Refractory MM (RRMM) – There’s a lot happening here. New agents such as selinexor – for which the MMRF funded early research to move it into clinical trials and supported the phase 2 STORM trial through its consortium – are showing promise in new trials. New combination studies of monoclonal antibodies with proteasome inhibitors and IMiDs are offering longer responses before relapse occurs. And another new drug, venetoclax (also studied in two MMRC trials, is showing great activity in combination with Velcade, particularly for patients with the 11;14 chromosomal translocation.

Transplant – Transplant is still considered an essential part of treatment for MM in the majority of patients. Autologous transplant is most common and safest. Allogeneic transplant or tandem transplant (having more than one transplant in a 3-6 month time period) may be options for very high risk patients. When considering a transplant, your age is not the only factor your doctor will consider; there is a “frailty scale” that your doctor can use to see if you are a good transplant candidate based on your current health. For frail patients it is important to balance the side effects of transplant drugs with how well they will work against your MM, and your doctor may give you fewer drugs at lower doses to control side effects.

MRD – The measurement of Minimal Residual Disease (MRD) is becoming more common, but questions still remain about doctors using it in their clinical practice. All agree it is important to achieve negative MRD (meaning no MM cells can be detected in the bone marrow) after therapy, and that staying MRD negative for as long as possible is a goal of treatment. In the future, MRD measurement might be done from a blood sample instead of a bone marrow sample, which will make it very easy for doctors to monitor how your disease is behaving and whether you may be relapsing.

Notes from the Clinical Trials session

  • Selinexor works in a way different from other MM drugs, so it can be combined with other therapies and offers good response especially for patients who have already taken many other types and combinations of MM drugs
  • Darzalex combined with Pomalyst and dexamethasone is showing very good activity in RRMM
  • Isatuximab is a new monoclonal antibody which is as active as Darzalex with milder infusion reactions and shorter infusion times at lower doses. The MMRC spearheaded the early combination trial with Revlimid and dexamethasone. It also shows good results in combination with Pomalyst and dexamethasone
  • Venetoclax works in a different pathway than other MM drugs, and is showing good response when combined with Velcade, particularly in t(11;14) patients

Notes from the transplant session

  • Having a transplant is still considered “standard of care” me aning that having a transplant causes most patients to live disease free for a longer time before they may relapse
  • Having a transplant earlier, right after you are diagnosed with MM, is important. If you wait, you may become sicker; then you may not be able to have a transplant because the treatment is difficult, with many side effects
  • Tandem transplant may help high risk patients, those who are del 17p, t(4:14), t(11:14)
  • It is too soon to tell if the monoclonal antibodies and other immunotherapies can be added to transplant treatment and if they might help. Studies are just beginning in this area
  • Older, frail patients may not be eligible to have a transplant if their doctor thinks it is too toxic for them
  • If necessary, even frail patients may be able to have a transplant if their doctor uses a doublet (2 drug) treatment instead of a triplet (3 drug) treatment, and uses a lower dose to help relieve the side effects

Notes from the MRD session

  • Once measurement of MRD becomes sensitive enough, doctors may be able to do the measurement from a blood sample instead of having to use a bone marrow sample
  • Knowing if you are MRD positive (MM cells were found in your sample) or MRD negative (no MM cells were found in your sample) will make it easier for your doctor to decide what therapy you need next, or if you can go off therapy
  • Ideally your doctor will monitor your MRD frequently to closely watch your disease and see if you are stable, responding to treatment, or relapsing
  • Becoming MRD negative after treatment may take a long time, maybe a year or more of staying on treatment until no more MM cells are detected
  • Becoming MRD negative does not mean you are cured, since you can still have a relapse; however, becoming MRD negative may mean that it will be a longer time before you have a relapse

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