When and how should MRD be measured in Philadelphia-negative ALL?

During the 2023 Society of Hematologic Oncology (SOHO) Congress, the ALL Hub spoke to Elias Jabbour, MD Anderson Cancer Center, Houston, US. We asked, When and how should MRD be measured in Philadelphia-negative (Ph−) ALL?

Jabbour begins by highlighting the importance of measurable residual disease (MRD) assessments in the treatment of Ph− ALL. He then outlines the various MRD techniques used to assess treatment response, including flow cytometry; polymerase chain reaction, which is mostly used in Europe and has a higher sensitivity level than flow cytometry of between 10^­−4 and 10⁻⁵; and next-generation sequencing (NGS), for which the highest sensitivity level is between 10⁻⁶ and 10⁻⁷.

He recommends early MRD monitoring in Ph− ALL; data shows that an early eradication of disease is associated with a better outcome, e.g., MRD-negativity measured by flow cytometry yields better outcomes if achieved by Day 21 compared with 3 months into treatment. His clinical practice approach involves assessing MRD by NGS and flow cytometry at the end of induction (Day 21 and Day 28); if measurements are still positive by NGS, measurements are repeated monthly until eradication. Once MRD negativity is achieved, it is measured every 3 months thereafter; early responders may require de-escalation of therapy and late responders may need to receive targeted immunotherapies, such as blinatumomab or CAR T-cell therapy.