Emerging Treatments in Multiple Myeloma Spark Prospect for Cure

James E. Hoffman, MD

With the development of novel therapeutic options, such as monoclonal antibodies and CAR T-cell therapies, the outlook for patients with multiple myeloma has significantly improved, said James E. Hoffman, MD. In fact, some of these approaches may even possess curative potential, he said, an idea that up until now has been unheard of in the space.

“We have an abundance of riches in terms of options for treating myeloma,” said Hoffman, an assistant professor of clinical medicine at Sylvester Comprehensive Cancer Center, University of Miami Health System. “A decade ago, the options were so limited that we would just throw medications at patients because we didn’t have any alternative options. Now, you can be much more diligent about choosing medications that won't hurt the patient.”

Currently, the different treatment approaches include proteasome inhibitors, immunomodulatory (IMiD) agents, and most recently, monoclonal antibodies. The 2 monoclonal antibodies that have received FDA approval in myeloma are daratumumab (Darzalex) and elotuzumab (Empliciti), both of which have shown impressive response rates when paired with IMiDs.

Beyond these antibodies, investigators are also evaluating the use of CAR T-cell therapy in this space, based on its observed success in other hematologic malignancies.

“This class of therapy, and more broadly, immunotherapies like this, hold a lot of promise—maybe even curative promise—for patients with relapsed disease,” said Hoffman, who cited bb2121, an anti-BCMA CAR T-cell product, to be furthest along in the developmental process.

OncLive^®: What treatments are currently available in multiple myeloma?

In an interview during the 2019 OncLive^® State of the Science Summit™ on Hematologic Malignancies, Hoffman discussed the current treatment options available for patients with multiple myeloma, underscored remaining challenges in the space, and shared predictions for where the field is headed.Hoffman: In multiple myeloma, there are really 3 main categories of therapy. There's a class of medications called proteasome inhibitors. Proteasomes are like the garbage cans of the cells, and if you paralyze them, myeloma cells really don't like that. There is a second category of drugs called IMiD agents. Thalidomide was the first in that category. The final category of agents are monoclonal antibodies.

Are there approaches under exploration in this space that you’re excited about?

What unmet needs still need to be addressed in this space?

There are multiple ways in which you can combine one drug from group A, one drug from group B, and one drug from group C, with different side effect profiles and different efficacies. We went through a couple of iterations where we used newer-generation drugs from each of those categories in combination and described the data both in terms of efficacy and adverse events.There is a class called CAR T-cell therapy, which is a type of immunotherapy that already has FDA-approved entities in the world of leukemia and lymphoma. In the world of myeloma, there has also been several advances. There are a few dozen drugs being evaluated in clinical trials. I highlighted 1 of those drugs, bb2121, which appears to be the farthest along.The problem with relapsed myeloma is two-fold. On one hand, these patients already got sick with their illness and had to undergo treatment. For many of them, that included a strong treatment like stem cell transplant. Therefore, they have a lot to recover from; their body has been through a lot.

Then, on relapse, they have an illness that can't be cured and hurts them in some capacity as it wakes back up. [When this happens], you have to throw new medications at them. You have a patient who is already sick with an illness, who has already been treated, who now needs to receive new medications.

How is the field evolving in the next 5 to 10 years?

Like in many related diseases, what we're looking for are highly efficacious, minimally toxic medicines. Myeloma is still an incurable illness in 2019, and in an ideal world, we would start to develop therapies that could offer curative potential so that patients could be treated for some finite period of time and then be able to go off therapy. Right now, the disease is treated more like a chronic illness, meaning patients remain on therapy. This is a big life burden for them—physically, financially, and emotionally. I would say a couple of things are probably going to happen. Some of the best drugs that we have for myeloma—including this class of monoclonal antibodies—are relatively new; they’ve only been around for about 3 to 3.5 years. That class of drugs is such a good addition to our treatment program.

What will happen is, this approach will get moved into the upfront setting. Basically, going forward, patients who have newly diagnosed myeloma will receive all the good medications that we already use, plus these monoclonal antibodies. The benefit of this approach will be that they won’t have additive toxicity. With that, you have more highly active initial treatments, you’ll get deep, durable benefit; maybe the relapses will happen much farther into the course of disease. Perhaps some patients won't even relapse.

What is your main takeaway for your colleagues who treat patients with multiple myeloma?

The best drugs that we have now will all get moved into the frontline setting and we'll get much better benefit initially. Hopefully, CAR T-type therapy or [a similar approach] where we can use really potent immunotherapies—will emerge in the relapsed sphere, offering the potential for a single treatment with durable, or even potentially curative, possibility.The drugs that we have now have very different side effect profiles and synergies with one another. Therefore, when we're treating patients in the myeloma clinic, we have a lot that we can do. We can mitigate toxicities; if someone has a problem with their heart, we won't use heart-toxic medications. If someone has a problem with their nerves, we won’t use nerve-toxic therapies.

We’re using therapies that have incredibly high efficacy and durability. As such, patients in the myeloma clinic can expect to have less toxic, more effective therapy equating to a longer and better life. Hopefully, over that longer and better life, new drugs will get approved by the FDA and patients with myeloma in 2019 won't die of their illness; they will die of something else or old age down the road. For the first time in the world of myeloma, the idea of this is possible to talk about.