Dr Shaji Kumar: Advances and Opportunities in Treating Multiple Myeloma

Despite the abundance of new drugs that have been approved recently and the promising clinical trials of other novel therapies, multiple myeloma remains incurable, explained Shaji Kumar, MD, professor of medicine at the Mayo Clinic. However, he believes that with better options for early intervention and personalized therapies, researchers are on a path to curing the disease.
Transcript (slightly modified)
What are some of the most promising new options in managing multiple myeloma?
A lot of new drugs have become available for treating myeloma, especially in the past few years. Some of the exciting new ones are the monoclonal antibodies which just got approved. We also have new drugs of the existing classes of proteasome inhibitors and immunomodulatory drugs. What is even more exciting is some of the drugs that are currently in clinical trials, which appear to be quite promising.
Among those are the immune checkpoint inhibitors, the PD-1 inhibitors. Pembrolizumab has been studied both in combination with pomalidomide and lenalidomide, and both of those initial studies look quite promising, and there are phase 3 trials ongoing.
There are some targeted therapies like venetoclax, which targets myeloma cells, especially those ones which carry the 11-14 translocation. This particular class of drug can also be combined with proteasome inhibitors, and that combination appears to be quite effective as well.
There are several other small molecule inhibitors, we have the CAR-T cell approach that has also been studied in myeloma with some very early results suggesting that it could be a promising avenue as well.
What are the opportunities for improvement in the current multiple myeloma treatment options?
Myeloma still remains incurable. With all the treatments that we have, we are able to control the disease for much longer than we could in the past. Patients are definitely living longer. A decade ago we had a median survival of 3 to 4 years, and now we have a median survival which is probably in the range of 8 to 10 years.
Now, patients inevitably relapse with all the current therapies, and sometimes when they relapse the disease becomes very difficult to control. So what we really need to do is to, one, develop new classes of drugs which can treat patients who become refractory to the current classes of drugs. We also need to understand what are the genetic or epigenetic mechanisms that drive these myeloma cells to become resistant to current therapies, so that we can actually enhance the efficacy of the current treatments and also allow these drugs to work for longer periods of time than what it is right now.
But what also is a very interesting opportunity going forward is the potential to intervene early in this disease. Now we know that patients with myeloma have this monoclonal gammopathy that has been going on for probably 10 to 15 years before they become symptomatic, so it also offers an opportunity for early intervention. We just need to have a better understanding of who is going to progress, and who is going to progress fast, so we can actually start treating those patients early with the hope that maybe we can cure the disease by intervening early.
What is your outlook on the future of multiple myeloma treatment?
I think it’s an exciting time in myeloma. We have a lot of new drugs. We have a better understanding of the biology. We just need to make bigger strides in matching the available treatments to the patients, so that we can get the best benefit with the least amount of toxicity. But certainly, we are on a path to a cure for this disease.
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