The Continued Rise Of Immune Checkpoint Inhibitors, CAR T-Cell Therapy & KRAS Inhibitors: These Are the Top Cancer Treatment Advancements of 2021

From immune checkpoint inhibitors to CAR T-cell therapy and KRAS inhibitors, there are various cancer treatment methods that gave patients more hope in 2021.

We spoke with leaders in the cancer world to get their take on the year's biggest treatment advancements, and this is what they had to say:

Cancer Treatment: Immune Checkpoint Inhibitors

Before getting into how immune checkpoint inhibitors have played a role in advancing cancer treatment this year, it is important to first understand what these drugs are.

Immune checkpoint inhibitors are a type of immunotherapy that block your body's immune checkpoint proteins from binding with partner proteins. Cancer cells sometimes find ways to use your body's checkpoints to avoid an attack by the immune system.

The Promise of Immunotherapy for Cancer Treatment

"What happens is that our systems or immune systems are geared to have various turning off points, various ways in which the immune system when it detects something that could be a potential threat, can be turned off or dialed down," Dr. Elad Sharon, a senior investigator in the Investigational Drug Branch of the National Cancer Institute Cancer Therapy Evaluation Program, tells SurvivorNet.

"And if we didn't have access to these types of drugs, essentially what we would be left with would be an immune system that doesn't really act in the interest of the patient to kill the cancer because of these natural … processes that make it so that we're not constantly inflamed, or constantly having the immune system under attack or attacking rather our tissue."

The U.S. Food and Drug Administration approved the first immune checkpoint inhibitor drug ipilimumab (brand name: Yervoy) in 2011. While this class of drugs is not new to the cancer world, immune checkpoint inhibitors have made major steps in 2021.

In fact, the FDA approved four different immune checkpoint inhibitors a total of 14 times this year. Pembrolizumab (brand name: Keytruda) was approved eight times; nivolumab (brand name: Opdivo) was approved four times; cemiplimab (brand name: Libtayo) was approved once; and atezolizumab (brand name: Tecentriq) was also approved once.

"If you were to ask me one of the big breakthroughs, not because it has just occurred in 2021, but because it is following the trajectory, is that the increasing utilization of immune checkpoint inhibitors … over a broader range of cancers, being more widely accepted and also bringing up earlier in treatment," Dr. Koh says.

"Oftentimes when you have a new drug that's brought in(to a patient's treatment regimen), it may be used after the second line or third line of treatment, but if it shows effectiveness, it may be brought up earlier in the course of treatment," he adds.

One approval Dr. Koh stresses the importance of is green light to use pembrolizumab for the treatment of early-stage triple-negative breast cancer, one of the most aggressive and most difficult-to-treat types of breast cancer.

Nobel Prize Winner: What's Next for Using Immunotherapy to Save Lives?

"Previously, (pembrolizumab) was used only for metastatic disease, but it's shown such a good response there that now is used for earliest-stage disease, not because they have metastasis, but because it's now been shown to reduce the risk of metastasis occurring."

Another example of immunotherapy drugs garnering additional approvals was in November when pembrolizumab was again approved by the FDA, this time for the adjuvant treatment (additional cancer treatment given after the primary treatment) of patients with renal cell carcinoma at an intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection (removal) of metastatic lesions.

In order to know if you are a viable candidate for checkpoint inhibitors as a treatment for your cancer, check with your doctor. They will go over your medical history to determine if this treatment is one of your best options.

CAR T-Cell Therapy: Moving Forward From CD19

Another cancer treatment advancement that has made significant progress in 2021 in CAR T-cell therapy.

"CAR T is a revolution in cancer therapy; it is paradigm changing," says Dr. Siddhartha Ganguly, previously the director of the lymphoma and myeloma program at the University of Kansas, and now the section chief of hematology at Houston Methodist Oncology Partners.

What is CAR-T Therapy?

It is important to first understand how this unique treatment method works:

Our immune system was designed to fight off foreign invaders such as viruses, bacteria and yes, cancer. But sometimes, cancer cells can evade detection and continue to grow. But CAR T-cell therapy essentially re-trains your immune system to make it a more efficient, and more effective, cancer fighter.

The process starts when your doctor intravenously removes a sample of your blood. With a procedure called leukapheresis the removal of blood to collect specific blood cells your blood flows into a machine that separates out the T-cells; it then returns the other blood components, such as red blood cells, platelets, etc.

The T-cells are then sent out to a lab, where technicians insert an anti-cancer gene into them. That new gene causes special receptors called chimeric antigen receptors to pop up on the surface of the T-cells. Those receptors are like homing devices that will lock onto the matching antigen on the surface of your cancer cells.

Once the T-cells are back from the lab, you will first need treatment to prepare your body to receive the new, genetically modified T-cells. "Patients are primed with three to four days of a mild form of chemotherapy, so that their body does not reject those genetically modified cells," Dr. Ganguly says. "And then those cells are infused, just like a blood transfusion."

Now that you know how this cancer treatment works, you are probably wondering how CAR T-cell therapy made big strides in 2021. Well, Dr. Koh says that the question at hand is: can CAR T-cell therapy ever expand past targeting the CD19 antigen? (CD19 is a tumor antigen, predominantly on leukemia and lymphoma cells.)

"The question has always been: can CAR T work for other cancers? Can CAR-T work for solid tumors?" he says. "That's still an area of investigation."

There is another question at hand about whether CAR T can be used a first-line treatment option rather than a second or third line, or a relapse of blood or plasma cancers like leukemia or multiple myeloma. Right now, CAR T-cell therapy is used after a patient’s first or second relapse.

Dr. James Hoffman, a hematologist focused on multiple myeloma and amyloidosis at the Sylvester Comprehensive Cancer Center at the University of Miami, tells SurvivorNet it’s possible that CAR T-cell therapy could eventually be utilized as a first-line therapy.

“Typically, in myeloma and in many other diseases, new drugs are designed for patients with relapse. These are patients with fewer options, and frankly, these are patients where new drugs can exhibit a benefit. That’s clear more quickly. We know the initial drugs in myeloma work very well,” Dr. Hoffman says.

“So, it’s a high hurdle to leap over with a new drug, but typically what will occur when you get a great drug in the relapse setting is it then starts to get tested earlier and earlier,” he adds. “And there are already trials that are ongoing incorporating these types of T-cell-directed therapies earlier and earlier in the treatment paradigm.”

Dr. Koh adds that he thinks one of the big advances this year was the FDA approval of the CAR T-cell therapy vicleucel (brand name: Abecma) for people with multiple myeloma that has not responded to or has returned after at least four different prior cancer treatments.

"Why I think it is interesting is that for the first time, it is not just targeting CD19," he adds. "It is targeting another specific target on myeloma cells called the B cell maturation antigen. So, why I find it interesting is that it is expanding the pool of patients for which CAR-T may become ultimately useful."

"The whole idea of CAR-T is you give these super revved up immune cells that attack a known cancer cell, but up till now, it has been limited to the cancer cells that express CD19. … This one (vicleucel) is unique in that it attaches and attacks to a certain antigen in the myeloma cells called the B cell maturation antigen."

CAR-T Cell Therapy: A ‘Revolution’ in Cancer Treatment

"If the idea is you can now engineer a CAR-T to attack something different, can you then move on to the next target?"

If you and your doctor are considering this treatment, "It behooves you to find out where your center is," Dr. Thomas Martin, a hematologist at University of California San Francisco Medical Center, tells SurvivorNet.

Even if a cancer center near you does not offer CAR T-cell therapy as a treatment, they may be studying it as part of a clinical trial in which you can enroll. And if you do have to go to a cancer center in another state, programs are available to help you cover the costs of transportation and lodging, including the Leukemia & Lymphoma Society's Susan Lang Pre CAR T-Cell Therapy Travel Assistance Program.

KRAS Inhibitors for Lung Cancer

"One thing I think has a chance to change, significantly, cancer outcomes is the approval of this drug called sotorasib," Dr. Koh says. This drug (brand name: Lumakras) is a KRAS inhibitor.

What is KRAS? KRAS is a gene mutation that occurs in some patients with non-small cell lung cancer and is generally associated with poor outcomes. According to Dr. Koh, this mutation drives the progression of cancer cells in a "significant" number of cancers about 30% of lung cancers, 40% of colon cancers and about 70% to 80% of pancreatic cancers.

One reason this mutation is considered a bad risk factor is that unlike other mutations, such as EGFR, there has never been a drug approved to treat this mutation. This changes with sotorasib; this cancer treatment was a big milestone.

For 30 years, Dr. Koh says, doctors thought KRAS had no druggability the likelihood of being able to modulate a target with a small-molecule drug. When developing a new drug, scientists and researchers look for weaknesses in a gene or mutation that can be targeted with the drug.

“But KRAS was this nice, round, smooth ball that they couldn't find what was targetable,” Dr. Koh says.

But that changed when sotorasib became the first FDA-approved KRAS agent. As mentioned, this drug is only approved as a second-line therapy for non-small cell lung cancer, “but I think it has the potential to be a game-changer either by itself or to introduce a whole new class of drugs to attack KRAS,” Dr. Koh says.

"… the needs being in lung cancer and colorectal cancer, and heavens knows we need something to make a big difference in pancreatic cancer when nothing has really raised that bar tremendously. So, if KRAS is over-expressed, say in 70 percent (to) 80 percent of pancreatic cancers, I think we could get that to be targetable."

"I just think that that is a potential game-changer," he adds.

Talk to your doctor if you think KRAS inhibitors could be right for you. Make sure your doctor performs genetic testing on your cancer so the best targeted therapy can be identified.

Learn more about SurvivorNet's rigorous medical review process.