Debu Tripathy

As our knowledge has grown regarding mutations in other hematological cancers that are being targeted by a growing array of drugs, MRD assays can detect not only relapse at its earliest stage but also what new mutations are evolving that lead to resistance and can be addressed by switching to the appropriate new drug.

It's been more than 20 years since treatment for patients with leukemia led the way in the development of testing for minimal residual disease, also referred
to as measurable residual disease (MRD). It was pretty clear then that the key to detecting very small amounts of tumor revolved around the tumor’s DNA.

That is because DNA is made of two chains of complementary base pairs, and these can be multiplied and expanded either naturally (when cells divide) or artificially in a test tube using a process called polymerase chain reaction that uses some of the enzymes that are required in nature. If one or more mutations of the tumor are known, these assays for tumor-specific RNA or DNA are ultrasensitive.

MRD testing began among patients with chronic myeloid leukemia, a disease that lends itself to gauging MRD because it is driven by a specific genetic mutation, the BCR-ABL fusion, which is part of the Philadelphia chromosome that can be viewed under a microscope. It became very useful when newer drugs became available that target the abnormal growth-promoting enzyme (kinase) encoded by this mutation. As our knowledge has grown regarding mutations in other hematological cancers that are being targeted by a growing array of drugs, MRD assays can detect not only relapse at its earliest stage but also what new mutations are evolving that lead to resistance and can be addressed by switching to the appropriate new drug.

 dedicated to issues facing patients with leukemia and lymphoma, we take a look at the history of MRD testing, talk with experts about its benefits for patients during their cancer journey and discuss how this technique may benefit more patients in the future.

“[MRD testing is] really the future for guiding the very best therapies,” one doctor told CURE. “Over and over again, we’ve seen examples of how MRD is the best predictor for outcome and (how) it can help us know when to increase or decrease or change therapies.”

In the future, more and more diseases will be managed in a more timely, precise manner with these technologies. 

Professor of Medicine
Chair, Department of Breast Medical Oncology The University of Texas MD Anderson Cancer Center

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Articles

MRD testing began among patients with chronic myeloid leukemia, a disease that lends itself to gauging MRD because it is driven by a specific genetic mutation. 

Minimal Residual Disease Remains An Evolving and Game-Changing Field

As we continue our transition to biologically and genomically directed cancer 

Professor and Chair
Department of Breast Medical Oncology The University of Texas MD Anderson Cancer Center

therapies, RAS gene mutations, that represent one of the first discovered, have remained an elusive target. 

Activating mutations in this class of oncogenes, specifically KRAS, have made a big step forward scientifically and clinically just in the last couple of years. Previously, 

 mutation, and as such has been one of the major unmet needs in our cancer armamentarium. This mutation not only leads to a more aggressive disease pattern in many cancer types, but also makes patients more resistant to other biological therapies. 

Through elegant cellular and molecular studies and innovations drug design, key advancements have been made to bring a new generation of drugs to the clinic.

Early results are showing great promise. One inhibitor, 

Lumakras (sotorasib), is approved by the Food and Drug Administration

 (FDA) to treat the KRAS G12C mutation in lung cancer. The approval came quickly following the results demonstrated in the CodeBreaK 100 clinical trial, making Lumakras the first targeted therapy for metastatic KRAS G12C-mutated NSCLC.

 benefited from being on the trial. She saw significant improvements in her symptoms within 10 days of being on the drug, and within four weeks had a noticeable decrease in the size of the tumors in her lungs. 

She was only able to take the drug for five weeks because tumors in her brain and spine continued to grow — but she attributes stabilization of the lung cancer to Lumakras.

, received FDA breakthrough therapy designation in June 2021. Additionally, a new drug application was accepted this February for patients with previously-treated KRAS G12C-mutated NSCLC.

All these drugs have made great headway; one patient even discusses that she felt she won the lottery after learning she had the KRAS-G12C mutation and was able to be treated with Lumakras. 

With more clinical trials underway, even more progress is around the corner for patients with KRAS G12C-mutated NSCLC. Ultimately, we expect to make progress in other cancers — notably in pancreatic cancer that exhibits KRAS mutations in 95% of cases, but predominantly affecting different base pairs in the same gene location: G12D, G12V and G12R. These mutations affect different amino acids on the KRAS protein and are not inhibited by Lumakras or adagrasib. 

Success on this front will require additional discovery, but important groundwork has been laid.

Activating mutations in this class of oncogenes, specifically KRAS, have made a big step forward scientifically and clinically just in the last couple of years. 

A Step Forward in Treating KRAS G12-Mutated Lung Cancer

The COVID-19 vaccines been one of the most talked about topics in recent years. It’s a moving target, with lots of information based on studies of the general population. So it is important for patients with multiple myeloma to understand what some of the uncertainties mean for them. In this special issue of 

®, we learn more about how patients with multiple myeloma are responding to the COVID‐19 vaccines and why their immune system’s response might not be as great as those without cancer.

Many patients with multiple myeloma are immunosuppressed because of faulty immunoglobulin production. This affects both cellular (specialized immune cells that recognize foreign antigens) and humoral (antibody‐based) immunity, causing a higher risk of bacterial infections and viral infections such as COVID‐19.

One way to fight the risk of contracting an infection such as COVID‐19 is to receive a vaccine, but is it as effective in patients with multiple myeloma?

Some patients may not make the same amount and quality of antibodies as people who don’t have cancer. But there is a wide spectrum of how immunosuppressed patients are and how they respond to a vaccine.

At this point we don’t know who will fully respond to the vaccine and who won’t. Many things can influence a patient’s response, such as their treatments or whether they have a higher tumor burden. We recommend these patients get vaccinated, first checking with their doctor about when the best time to do so is, depending on their treatment cycle.

As the omicron variant spread, we learned that although it is more transmissible, it is not as virulent. This means all of us are more susceptible to the variant and may have to take more precautions to protect ourselves against it, but if infected we are less likely to have a severe case of COVID‐19.

We recommend that patients with multiple myeloma get the standard vaccines and boosters for COVID‐19. Remember, even if you don’t get full immunity, some immunity is better than none.

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Many things can influence a patient’s response to the COVID-19 vaccine, such as their treatments or whether they have a higher tumor burden.

Some Immunity Is Better Than None Against COVID-19

Our country, as well as the rest of the world, is uneven in how society is treated based on many unalterable factors such as race and ethnic heritage — characteristics that permeate just about every aspect of daily life. In health care delivery, such disparities are well documented and are further complicated and magnified by associated factors such as education level, income, employment and access to care. Cancer care is among the most expensive and complicated medical deliverables and, perhaps, the most affected by racial disparities. Imbalances among racial groups that exist in many corners permeate every dimension of cancer, from lifestyle and preventive aspects to availability of cancer screening, timely diagnosis of cancer and rapid access to treatment and follow-up. Because research into this topic has increased in the past few decades, this subject has come to the forefront of government officials, the health care industry, businesses that provide and purchase health care coverage, and the public in general.

How has this information influenced policy and laws? Has it really helped level the playing field for all races and ethnicities? Are cancer outcomes starting to improve for affected racial groups?

In this issue of CURE®, you will learn more about these disparities and some of the underlying reasons we find ourselves in this situation. You will read about examples of and possible reasons for racial inequities in different parts of patients’ cancer journeys.

A deeper dive into specific ethnic and racial groups will provide some context and personalize this problem — illustrating that we all own it and need to address it as a society. As is our tradition, you will get specific facts and figures that illustrate the magnitude of the problem. For example, postoperative mortality after cancer surgery has improved over the years, but there is still a gap in death rates — it remains higher for Black patients compared with White patients, according to a large analysis using national Medicare data. Disparities in outcomes also exist for Hispanic/ Latino patients with cancer.

The past year has spotlighted racial inequities not only in the U.S., but worldwide. It has also opened our eyes as to how a major health disruption — in this case, a pandemic — can aggravate the unacceptable status quo. This issue will also provide some hopeful and positive new trends on both small and large scales that we hope can move us toward greater cancer care equality.

The past year has spotlighted racial inequities not only in the U.S., but worldwide. It has also opened our eyes as to how a major health disruption — in this case, a pandemic — can aggravate the unacceptable status quo.

Debu Tripathy

Minimal Residual Disease Remains An Evolving and Game-Changing Field

A Step Forward in Treating KRAS G12-Mutated Lung Cancer

Some Immunity Is Better Than None Against COVID-19

Examining Racial and Ethnic Disparities in Cancer Care

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