Myeloma’s “Achilles Heels” at IMW 2017
Hello from New Delhi, India!
Every two years, the myeloma research and clinical community gathers for a meeting called the International Myeloma Workshop; it is the largest meeting focused exclusively on myeloma and related diseases. The meeting typically attracts more than 3,000 attendees from all over the world. This year’s meeting is being held in India, and the MMRF is on-site to report on the latest findings.
The first session, a talk by Dr. Ken Anderson from the Dana-Farber Cancer Institute in Boston (and an MMRF Board Member), dealt with how to attack myeloma where it is most vulnerable – its so-called Achilles Heels. There are three areas that are most promising right now:
- Drugs that work by changing the way myeloma cells survive: an example of this type of drug is the proteasome inhibitor Velcade . There are new targets, called DUBS (deubiquitinating enzymes) that can be inhibited by new drugs; these act in a similar manner to Velcade and other proteasome inhibitors but at different points in that same pathway, and may be useful to patients for whom Velcade is no longer effective.
- Drugs that enable a patient’s own immune system to recognize and kill myeloma cells: the monoclonal antibodies Darzalex, Empliciti, and the checkpoint inhibitors (targeting PD1 and PDL1) are showing great activity in combination treatments with proteasome inhibitors (like Velcade) and immunomodulatory drugs (IMiDs like Revlimid). There are now many exciting clinical trials in this area using these combination approaches to provide longer remission periods for myeloma patients. Cancer vaccines and CAR-T cell approaches continue to advance in the clinic, and these may also someday become more common as doctors find new ways to make them even more active against myeloma and less toxic to patients.
- Drugs that work against specific genomic alterations: the BCL-2 inhibitor venetoclax is now in the clinic in a phase 3 trial in combination with Velcade and dexamethasone. Studied extensively in MMRC trials, there are data strongly suggesting that this therapy works best in patients with t(11:14).
Dr. Anderson ended his talk by saying that the two critical things to achieve cures for MM are 1) to find drug combination which can get patients to MRD (minimal residual disease) negative status, meaning that their MM cells are no longer detectable in the body at the end of a course of therapy, and 2) the use of combination therapy to restore the patients’ immune system so it can recognize and kill any remaining MM cells.
The next set of talks focused on new trials for smoldering myeloma (SMM) patients, and whether or not SMM patients should receive treatment or just be observed to carefully check if their disease is progressing to MM. Some findings were:
- High risk SMM patients do benefit from receiving therapy and therapy improves their overall survival
- The question of what makes a SMM patient high risk has still not been fully answered, but there is a lot of work going on right now in this area
- tTe question of what causes a SMM patient to progress to MM has not been fully answered yet, but researchers are looking closely at what happens in the bone marrow surrounding the myeloma cells to try to define how the myeloma cells survive and thrive there.
- The disadvantages to treating SMM patients include side effects of the current anti-myeloma drugs and the fact that their disease may become more aggressive with treatment
- The advantages of treating SMM patients include an improvement in survival in high risk SMM patients and the fact that disease may become less aggressive with treatment
- Some SMM patients can benefit from being treated with Darzalex but do not want to sit through an 8 hour infusion. A new type of Darzalex is being developed which is given under the skin (subcutaneously) which can be given much faster and is as effective and as safe.
Early afternoon sessions summarized results of some ongoing MM clinical trials:
- The STAMINA trial showed that having a tandem autologous stem cell transplant did not improve survival compared to a single autologous stem cell transplant
- Velcade-Revlimid-dexamethasone showed similar survival benefit to Revlimid-dexamethasone in newly diagnosed patients
- Patients who received maintenance therapy with Revlimid after autologous stem cell transplant saw significantly increased overall survival compared to patients who received no maintenance therapy
- Patients over 75 years old experienced greater cardiovascular side effects with Kyprolis compared to younger patients, especially high blood pressure. Side effects can be managed by lowering the dose level or stopping the drug; elderly patients should be carefully screened for pre-existing cardiovascular problems before starting Kyprolis therapy
The day ended with a session on immune-oncology therapies, such as checkpoint blockers (PD1/PDl1 monoclonal antibodies). These agents have not shown activity in MM by themselves but do show promise when used in combination with other therapies such as proteasome inhibitors and IMiDs. More work on dosing regimens is needed to determine how MM patients can truly benefit from them. Also discussed were CAR-T cell therapy, cancer vaccines, and newer bispecific antibody therapies. While each of these new therapies has shown some promise, positive results have been seen in only a few patients, and significant side effects were seen with some therapies, notably CAR-T cell therapy. Researchers continue to investigate the biology of MM and the effects of patients’ own immune systems to determine if MM patients can truly benefit from these treatments.
More to come tomorrow!
By Mary DeRome, Director Medical Communications and Education, MMRF