Undetectable Minimal Residual Disease Associated with Long-Term Survival in CLL

Minimal residual disease (MRD) is a term used to describe the small number of cancer cells that remain in the body after treatment.¹ In a patient with MRD, the number of remaining cancer cells can be so few that they do not experience any symptoms. However, over time, these cells may begin to multiply, causing a relapse. Testing for MRD can show whether treatment has been completely effective.¹ If a patient with cancer, such as chronic lymphocytic leukemia (CLL), is “MRD positive,” a small number of cancer cells can be detected using sophisticated testing methods. In contrast, patients who are “MRD negative” have no evidence of residual cancer.¹

 Cancer specialists believe that MRD status is an excellent predictor of progression-free survival (PFS) and overall survival (OS) for people with CLL. “[Patients with CLL] who achieve undetectable minimal residual disease…[after treatment with chemoimmunotherapy] have better outcomes than those with detectable MRD,” said Stefano Molica, MD, Medical Oncologist, Hematology-Oncology Department, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy.² Based on this understanding, Dr Molica and colleagues reviewed clinical trial reports to assess whether extension of PFS and OS are truly different for patients with CLL who achieved undetectable MRD after initial treatment with chemoimmunotherapy.^2,3

Dr Molica and colleagues reviewed published data from 11 large clinical trials that enrolled more than 2400 patients with CLL who received initial treatment with chemotherapy or chemoimmunotherapy. Of these 11 studies, 9 (which enrolled 2088 patients) provided data on the impact of MRD on PFS. Six of the 11 studies (which enrolled 1234 patients) provided information on the impact of MRD on OS. In 2 of the 11 studies (which enrolled 213 patients), MRD was the primary measure of treatment efficacy.³ After combining data from these studies, researchers found that patients who lived longer in total (OS) and those who lived longer without evidence of disease (PFS) after receiving chemotherapy or chemoimmunotherapy were more likely to be MRD-negative.³

Today, chemotherapy-free treatment regimens (regimens that contain targeted drugs, such as venetoclax [Venclexta], acalabrutinib [Calquence], and ibrutinib [Imbruvica]) are being used more often in the first-line treatment of CLL, especially among older patients with other medical conditions.³ It will be important for doctors to determine whether MRD status can predict long-term survival after treatment with targeted drugs. Researchers are also exploring whether MRD status can be used to decide whether patients with CLL can take a break from treatment. These questions will be answered in future clinical trials and literature analyses.

References

1. Leukemia & Lymphoma Society. Minimal residual disease (MRD). April 2019. www.lls.org/sites/default/files/National/USA/Pdf/Publications/FS35_MRD_Final_2019.pdf. Accessed May 3, 2020.
2. Oncology Learning Network. Undetectable MRD status associated with long-term survival in CLL. www.oncnet.com/news/undetectable-mrd-status-associated-long-term-survival-cll.
3. Molica S, Giannarelli D, Montserrat E. Minimal residual disease and survival outcomes in patients with chronic lymphocytic leukemia: a systematic review and meta-analysis. Clin Lymphoma Myeloma Leuk. 2019;19:423-430.