Getting to Zero: MRD Yardstick for Myeloma Inches Closer

Marijke Vroomen Durning, RN
Published: Friday, Jan 29, 2016
C. Ola Landgren, MD, PhD

C. Ola Landgren, MD, PhD

Minimal residual disease (MRD) is routinely used to monitor treatment response in hematologic malignancies such as acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL).1,2 Now, researchers and oncologists are excited about the prospect of MRD becoming equally useful in the assessment and management of patients with multiple myeloma, particularly in light of the development of new, more effective therapies and the current limited ability to assess their effectiveness.

The rapid rate of research into myeloma treatments has outpaced testing. Ten new drugs have been approved during the past decade, giving physicians hundreds of possible combinations to work with.3 For the 50 years before that, there were only two drugs for usual treatment: melphalan and steroids.

From 1975 to 1999, the 5-year survival rate for myeloma ranged from 26.6% to 31.1%.4 By 2007, the rate had reached 45.1%. So until recently, there was no real push to study for response in myeloma as there was for the leukemias, C. Ola Landgren, MD, PhD, said in an interview with OncologyLive. Very few patients with myeloma even reached a complete response, he said. Landgren is chief of Myeloma Service at Memorial Sloan Kettering Cancer Center (MSK) in New York City.

Landgren predicts that with the new therapies, myeloma survival will double. “We recently did a simulation model that we are going to present at the AACR [American Association for Cancer Research] in 2016,” he explained. “Five years ago, we were at around 23,000 newly diagnosed patients in 1 year in the United States. This past year, we were at about 25,000, and in 5 years, we project that it will be about 26,000 or 27,000.” Five years ago, the number of people in the United States living with myeloma was around 50,000 to 55,000, Landgren said. “This year, the estimation is that there are around 80,000. We think that in 5 years, there will be more than 120,000 people in the United States living with myeloma. It’s going to skyrocket.”

The new drugs used to treat myeloma have become so effective that achieving a complete remission in the newly diagnosed patient population is expected, Blake A. Morrison, PharmD, vice president, Medical and Scientific Affairs, Multiple Myeloma Research Foundation (MMRF), said in an interview.

“In clinical trials, we’re now achieving complete remissions along the line of 60% to 80% of the time, and in general practices, it’s probably closer to 40% to 50%. What we find, though, is that for some patients who achieve a complete remission, the remission will last for 3 years, and for some of them, it will last for less than a year. There’s great variation in terms of the complete remission and what it ultimately achieves.”

But without the ability to assess patient response to treatment, physicians are limited in trying different new drug combinations and in determining which patients will fall into which remission category after treatment.

Testing for MRD

A growing body of evidence has demonstrated that MRD-negative status is an achievable goal that is “predictive of superior outcomes” for patients with multiple myeloma,5 but development of the technical standards for measuring and defining that status has proved complex. National Cancer Institute researchers have found that major medical centers in the United States vary considerably in MRD flow cytometry definitions and standards. Flanders et al reported “considerable variation” in the number of bone marrow cells analyzed and the number of abnormal plasma cells used to define MRD status, as well as a 100-fold difference in sensitivity methods, among 11 centers (out of 26 surveyed) conducting MRD testing by flow cytometry.6

Researchers have been working to standardize testing methods and MRD definitions. The International Myeloma Foundation (IMF) has partnered with a consortium of 13 countries to create an automated flow cytometry test that is sensitive to 10-6 (1 cell in a million).7 The organization believes both the patient’s bone marrow and blood should be MRD negative by that standard, confirmed by a negative PET CT scan and a normal heavy/light ratio.7

Trends in Multiple Myeloma

Trends in Multiple Myeloma

SEER Stat Fact Sheets: Myeloma. National Cancer Institute; Surveillance, Epidemiology, and End Results Program. Accessed January 18, 2016.

The ASCENT clinical trial, expected to be launched in the United States this year, will utilize the IMF test to correlate the effectiveness of an aggressive treatment strategy for patients with high-risk smoldering myeloma, which the group believes could result in cures for as many as 30% to 50% of participants.8 A similar clinical trial started in Spain last year.

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