Jerald Radich, MD, an associate professor of Medical Oncology at the University of Washington School of Medicine, and member of the Clinical Research Division at the Fred Hutchinson Cancer Research Center, discusses the impact of minimal residual disease (MRD) on survival outcomes in patients with acute myeloid leukemia (AML).

Over the years, a fair amount of data in transplant eligible and ineligible patient populations have indicated that those who are MRD positive have a significantly higher risk of relapse vs MRD-negative patients—approximately 2- to 3-fold, Radich says. A large analysis with 10,000 patients from multiple studies was recently conducted and results demonstrated that MRD was consistently associated with relapse and overall survival, Radish explains. The association was observed regardless of age, treatment, and whether MRD was defined by flow cytometry or genetic testing, Radich notes.

Overall, MRD positivity in this patient population is associated with negative outcomes, according to Radich. Approximately 30% of patients who are MRD positive will not relapse, while approximately 30% of patients who are MRD negative will, Radish concludes.

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Jerald Radich, MD, discusses the impact of minimal residual disease on survival outcomes in patients with acute myeloid leukemia.


Dr. Radich on the Impact of MRD on Survival Outcomes in AML

Jerald P. Radich, MD, member, Clinical Research Division, Fred Hutchinson Cancer Research Center, and professor, University of Washington School of Medicine, discusses measuring minimal residual disease (MRD) in hematologic malignancies.

The optimal way to measure MRD can vary between diseases, says Radich.

However, flow cytometry is a commonly utilized modality that measures aberrant antigen presentation on cells, says Radich. Flow cytometry has a sensitivity of 1 leukemia cell in 1000 to 10,000 polymerase chain reaction (PCR)—based detection. PCR-based detection looks at translocations or point mutations.

Next-generation sequencing (NGS) is another option of measuring MRD, explains Radich. Although NGS looks at translocations and point mutations comprehensively, it is less sensitive compared with flow cytometry and may not be cost effective.

Other MRD testing methods, such as single-cell genomics, are beginning to emerge and aim to decipher the complex nature of clonal evolution, says Radich.

Jerald P. Radich, MD, discusses measuring minimal residual disease (MRD) in hematologic malignancies.

Dr. Radich on Measuring MRD in Hematologic Malignancies

Jerald P. Radich, MD, member, Clinical Research Division, Kurt Enslein Endowed Chair, Fred Hutchinson Cancer Research Center, and professor, University of Washington School of Medicine, discusses the utility of minimal residual disease (MRD) in hematologic malignancies.

MRD status can be used to predict long-term responses in acute leukemias like acute lymphoblastic leukemia and acute myeloid leukemia, says Radich. A patient who is MRD positive following induction or consolidation therapy is at an increased risk of relapse after transplant. MRD can also shed light on the biology of the disease, explains Radich.

In chronic myeloid leukemia (CML), the depth of patients’ major molecular response is used to determine which patients can discontinue treatment, says Radich. The same principles may be used as a model in chronic lymphocytic leukemia and multiple myeloma where prolonged rates of MRD negativity may guide when patients can discontinue maintenance therapy, concludes Radich.

Jerald P. Radich, MD, discusses the utility of minimal residual disease in hematologic malignancies.

Dr. Radich on the Utility of MRD in Hematologic Malignancies

Jerald P. Radich, MD, member, Clinical Research Division, Kurt Enslein Endowed Chair, Fred Hutchinson Cancer Research Center, and professor, University of Washington School of Medicine, discusses the impact of minimal residual disease (MRD) in patients with acute versus chronic leukemias.

Any level of MRD positivity is associated with bad outcomes in acute leukemias, says Radich. If patients with acute lymphoblastic leukemia or acute myeloid leukemia are MRD positive at the end of induction or consolidation therapy, their risk of relapse increases 3- to 5-fold compared with patients who achieve MRD negativity, adds Radich.

MRD does not appear to impact those with chronic leukemias as intensely. In fact, patients with chronic lymphocytic leukemia, multiple myeloma, or chronic myeloid leukemia can have low levels of MRD and not experience relapse, according to Radich. If levels of disease are low enough, patients can still have presence of their disease by MRD without necessarily being at high risk of relapse, concludes Radich.

Jerald P. Radich, MD, discusses the impact of minimal residual disease in patients with acute versus chronic leukemias.

Dr. Radich on Impact of MRD in Acute Vs Chronic Leukemias

Jerald P. Radich, MD, member, Clinical Research Division, Fred Hutchinson Cancer Research Center, and professor, University of Washington School of Medicine, discusses how the role of minimal residual disease (MRD) has evolved recently in clinical trials of hematologic malignancies.

MRD is measuring the disease burden, says Radich. It is used to define a patient’s response to therapy. However, not only is it used to predict relapse, but it can also be used to get an understanding of how some therapies may be more active than other therapies.

The FDA began to use MRD as an early marker of response, but now a lot of work is being down in acute leukemias using MRD as an endpoint in clinical trials. This is also being used in some chronic leukemias, as well. MRD has been strongly associated with later outcomes, Radich says.

Jerald P. Radich, MD, discusses how the role of minimal residual disease (MRD) has evolved recently in clinical trials of hematologic malignancies.

Dr. Radich on the Evolving Role of MRD in Hematologic Malignancies

Jerald P. Radich, MD, clinical research division, Fred Hutchinson Cancer Research Center, discusses compliance to the NCCN guidelines in the treatment of patients with chronic myeloid leukemia (CML).

A few years ago, 2 surveys were sent to physicians to assess the discrepancy between what physicians believe they are doing when treating patients, and what they actually do, says Radich. One survey was sent to 100 physicians asking the importance of the NCCN guidelines and whether they follow them. One hundred percent of physicians responded that they were exceedingly important, says Radich.

Another survey was done through a health registry where investigators could see exactly how many CML patients had molecular testing done. It is recommended that patients receive testing every 3 months, but the survey found that only 50% of patients were being tested once a year. Though adherence to the guidelines is better than it used to be, it still needs to be emphasized that the guidelines exist to aid physicians in making treatment decisions, says Radich.

Dr. Radich on Compliance to NCCN Guidelines in CML

Jerald P. Radich, MD, clinical research division, Fred Hutchinson Cancer Research Center, discusses treatment discontinuation off trial for patients with chronic myeloid leukemia (CML).

About 50% of patients who reach a deep molecular response for several years are able to discontinue therapy and stay free of disease for about 2 to 3 years, says Radich.

It is strongly recommended that this is done solely on a clinical trial, says Radich, but the NCCN recognizes that physicians may attempt to do this off of a clinical trial, so guidelines have been put into place for physicians to follow. Radich explains that a patient has to be on drug for at least 2 years and have a documented deep response for more than 2 years; they cannot show up in the clinic one day with a good partial complete response.

After discontinuation, patients must be monitored every month for 6 months. Because of all these criteria, only a small percentage of patients should attempt to be discontinued off a clinical trial, concludes Radich.

Dr. Radich on Treatment Discontinuation in CML Off Trial

Jerald P. Radich, MD, clinical research division, Fred Hutchinson Cancer Research Center, discusses the potential of biosimilars in oncology.

Biosimilars have a lot of potential in oncology, explains Radich, but one of the concerns about biosimilars is their efficacy in comparison to their originator biologics. Radich notes that it is very unlikely that a biosimilar is going to reach the clinic without having met the standards that are in place for approval.

Nonetheless, it may take a while for people to become familiar and comfortable with the use of biosimilars in oncology, says Radich. In addition to the recent approvals of the bevacizumab (Avastin) biosimilar ABP-215 (bevacizumab-awwb; Mvasi), and the trastuzumab (Herceptin) biosimilar MYL-1401O (Ogivri; trastuzumab-dkst), several biosimilars are in development for the treatment of patients with cancer.

ABP-215 was the first oncologic biosimilar to be approved in the United States. The Amgen and Allergan product was approved for the treatment of adult patients with colorectal, lung, brain, kidney, and cervical cancers.

Dr. Radich on the Potential of Biosimilars in Oncology

Jerald P. Radich, MD, clinical research division, Fred Hutchinson Cancer Research Center, discusses which patients should receive the newly approval generic imatinib versus second-generation tyrosine-kinase inhibitors (TKIs) in chronic myeloid leukemia (CML).  

It is important that oncologists are proactive in determining which patients should receive generic imatinib and not be registered by insurance companies, says Radich.

The NCCN guidelines are somewhat generic, and so oncologists need to look at each patient individually and, based on treatment goals, determined if they should receive generic imatinib or second-generation TKIs. Age may be a factor to consider, says Radich.

​Jerald P. Radich, MD, clinical research division, Fred Hutchinson Cancer Research Center, discusses which patients should receive the newly approval generic imatinib versus second-generation tyrosine-kinase inhibitors (TKIs) in chronic myeloid leukemia (CML).  

Dr. Jerald P. Radich on Treatment Considerations with Generic Imatinib in CML

Jerald P. Radich, MD, clinical research division, Fred Hutchinson Cancer Research Center, discusses the impact of the approval of generic imatinib in chronic myeloid leukemia (CML).

Generic imatinib, which seems to have the same toxicity and efficacy as branded imatinib, should really be substituted in wherever branded imatinib is normally used, says Radich. However, second-generation tyrosine-kinase inhibitor (TKIs) should still be used for patients that will benefit more from those agents.

Generic cancer drugs are needed in the United States, says Radich, as drug prices are extremely high. Branded imatinib, and second-generation drugs, are roughly about $100,000 a year, he says. Usually the price of a generic agent is roughly 40% of the branded agent when it first comes out. As competitive builds, the prices drop down even more, says Radich.

View more from the 2016 NCCN Hematologic Malignancies Congress

​Jerald P. Radich, MD, clinical research division, Fred Hutchinson Cancer Research Center, discusses the impact of the approval of generic imatinib in chronic myelogenous leukemia (CML).

Jerald P. Radich, MD

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