In the past 20 years, clinical research studies have led to new treatments for blood cancers such as leukemia, lymphoma, multiple myeloma, and myeloproliferative neoplasms (MPNs). Breakthrough therapies have helped many people with blood cancers live longer and improve their quality of life. So why do so many people living with blood cancers consider participation in clinical trials a last-ditch effort, an option only when no other treatment has worked?

MyHealthTeam spoke with Dr. Greg S. Nowakowski about clinical studies for blood cancers. Dr. Nowakowski is a hematologist and the Enterprise Deputy Director for Clinical Research at Mayo Clinic Comprehensive Cancer Center. He’s led many research studies to find new treatments for leukemia, lymphoma, and multiple myeloma and worked on better ways to design clinical trials.

Here are Dr. Nowakowski’s answers to our questions about clinical studies for blood cancers — what success means in studies, the potential benefits and downsides, and whether joining a clinical trial is a good option for people with blood cancers.

What’s the Goal in Clinical Trials for Blood Cancers?

Clinical trials can have different goals. The majority of clinical trials are looking at the effectiveness of drugs. Are they better than the standard of care [what’s currently used to treat this cancer]? In cancer clinical trials, typically we do not use placebo or so-called “sugar pills.” So everybody gets at least standard therapy, but on top of this standard therapy, we add the new therapy, or we just [compare the] new therapy against the standard of care. In those advanced clinical trials, the question is: How much better is this new treatment over what we use now?

What Does ‘Cure’ Mean When It Comes to Blood Cancers?

Cure is defined as the cancer not coming back over a period of time. For most blood cancers, the aggressive ones like acute leukemia or lymphoma or even myeloma, if we do not see the cancer cells come back over a period of two to five years, we can say that this cancer is most likely cured.

What Is a Functional Cure?

Ideally, we'd like to cure those cancers and have a guarantee they’ll never come back. But if we have a treatment which can control it for a very long time with little side effects and without impact on the quality of the patient’s life, it’s very meaningful. We call this a functional cure.

The functional cure is a little bit like controlling blood pressure or diabetes. We may not be able to cure this condition, but with the treatments we have, we can actually control it so well that patients are asymptomatic [don’t have any symptoms].

We may have to use the treatment periodically to shrink the tumor or keep it under control. We know there is some chance that the disease can come back, and at some point we will have to treat it again. This ability to induce durable disease control in between the treatments is an important measure of success that’s happening in certain cancers, including myeloproliferative disorders, slowly growing lymphomas, and some slowly growing leukemias.

How Is Success Measured in Clinical Trials for Blood Cancers?

Success in clinical trials is dependent on what kind of a clinical trial it is, but in general we would like to see [a new treatment’s] ability to control or cure the cancer and minimize the impact on patients’ lives.

Progression-Free Survival

There is a short-term goal of making the tumor disappear completely, and there’s a long-term goal of preventing this cancer from coming back, ideally curing it. In this case, the success of the study is measured in progression-free survival, which means that people live without cancer recurrence [cancer coming back].

Complete Remission

Success is sometimes measured by measuring the tumor. In the case of lymphoma, we measure the tumor directly on the imaging studies. In multiple myeloma, we measure monoclonal protein called the M spike, and we would like it to disappear. In acute leukemia, you have to look at the bone marrow biopsy and see if the leukemic cells are completely gone. It’s called complete remission when we do not see any residual cancer.

Minimizing Side Effects

We do also look at the severity of side effects from therapy, with the goal of new treatments having less side effects while maximizing the efficacy.

Why Can Blood Cancers Be Difficult To Cure?

Some blood cancers originate at a very early stage of the cell’s development, the stem cells. These are very primitive cells that give rise to many different blood cells in our body. Those stem cells are quite difficult to eradicate. If [genetic] mistakes happen in the stem cells, the disease can persist. We can treat it and eradicate some of the cells causing cancer, but not necessarily the stem cells, the very seeds [of cancer].

We hope that [new] immunotherapies will be able to eradicate even those seeds. So if the seed starts to grow again, the immune system immediately takes care of it in our body. We also have clinical trials where we look at very early [problems] in stem cells and try to intervene before the cancer even develops. It’s a whole new fascinating area called cancer interception.

What Are the Benefits of Participating in Trials for Blood Cancers?

By being in clinical trials, you have access to the most modern treatment, the most cutting-edge treatment, which can improve your outcome. I have patients now, which I have followed for many years, who are only here because they had early access to clinical trials with unprecedented results. If I was to treat them with standard therapy at the time, unfortunately the outcome would not be as good. But because they were able to access this new treatment in clinical trials, they’re essentially cured.

I can honestly say that if any of my family members were to be diagnosed with cancer, I would strongly recommend being on a clinical trial.

What Are the Downsides of Joining a Cancer Clinical Trial?

One of the downsides is that you need to adhere to a certain schedule with closer observation and maybe see the doctor more than you would normally do. Some patients like it; some patients say, “It’s just too much for me. I don’t want to commit myself.”

I don’t think many of our patients have a problem with it. In fact, they like this additional safety net and having the attention of this team.

Are Clinical Trials the Last Option for Treating Blood Cancer?

By no means should clinical trials be a last-ditch effort. I’m leading studies which are not the last option. It’s the opposite — they’re actually designed as the first option of treatment. For example, in aggressive lymphomas, we can cure about 60 percent of them with front-line treatment, but unfortunately 40 percent will relapse [the cancer will come back]. In front-line studies, we keep adding new medications or new approaches to improve this cure rate upfront.

I deeply believe the best chance of curing cancer is with the first treatment. Some drugs [currently used] later on in the disease course [can be] moved to the front line to maximize our initial treatment to get rid of the cancer.

What’s New in Blood Cancer Treatment?

MyHealthTeam asked Dr. Nowakowski to highlight a few of the most promising developments currently happening in blood cancers.

Lymphoma

In lymphoma, we have recently seen a revolution with new treatments, particularly immune therapies — bispecific antibodies and cellular therapies. The outcomes of patients [were already] dramatically improving because of these advances, but we also take those new drugs and combine them in new ways. We have seen advances both in terms of disease control and survival. There are a number of very exciting trials in lymphoma.

Multiple Myeloma

The same is true about multiple myeloma. [We] have been combining new classes of drugs which are very active, and patients with multiple myeloma are surviving longer than ever before. We see increased cure rates in multiple myeloma. We still consider this disease to be largely incurable, but we do see this functional cure with treatments [that allow] the disease to be controlled for a very long time.

Leukemia

Similar approaches with immunotherapy are moving to leukemia as well. In addition, in leukemia we have a number of targeted agents which are being combined with front-line therapy to increase cure rates.

Myeloproliferative Neoplasms

In myeloproliferative neoplasms, there are really two questions. One is the disease control itself, but also controlling symptoms, because the disease itself can be very slowly progressive. For that, there are a number of new classes of drugs which are very effective, which are being currently studied in the clinical studies early on.

How Can People Access These Advances in Cancer Treatment?

The best way of benefiting from this progress is to [join] a clinical trial. This provides access to the most modern and best therapy. We should not think about clinical trials as an afterthought. In fact, you should think about us as a best option, including for front-line therapy. Billions of dollars have been spent on the development of these new drugs, and the field is changing. I would encourage all patients to be seen at centers that have trials open and to participate in clinical trials.

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