Minimal Residual Disease Positivity After Treatment Could Lead to Worse Outcomes in MCL

Minimal residual disease (MRD) positivity after induction and consolidation therapy appeared to be associated with worse progression-free and overall survival in patients with mantle cell lymphoma (MCL), according to study findings published in the Journal of Cancer.

Patients with advanced MCL tend to be treated with high-dose chemotherapies, chemoimmunotherapies and nonchemotherapeutic agents, such as front-line induction treatment, autologous stem cell transplantation (ASCT) consolidation or Rituxan (rituximab) maintenance after ASCT. Unfortunately, despite some survival benefit, most patients will relapse eventually.

“Also, the toxicities and economic burden from consolidation and maintenance treatment can still be the problems,” the researchers said. “Therefore, early assessment of treatment efficacy and response- guided therapy are necessary in MCL management.”

MRD refers to a small number of cancer cells that are left in the body after treatment, and can also play a role in determining whether the disease has the potential of coming back and causing a relapse. In recent years, studies have shown that MRD could provide evidence for early response of treatment efficacy.

“Previous studies showed that MRD assessment could predict survival outcomes in MCL,” the researchers added. “Also, in some previous clinical trials, surveillance of MRD can monitor response to prior therapy and may inform the need for further consolidation or maintenance therapy in MCL.”

However, despite previous trials being conducted in this area, according to the researchers, the sample sizes of each study were typically small. Therefore, the researchers conducted a meta-analysis to further understand the impact of MRD on survival outcomes in newly diagnosed MCL.

Ten articles were included in the quantitative meta-analysis, with all 10 reporting on MRD-related progression-free survival, or the time from treatment to disease progression or worsening, and six reporting on MRD-related overall survival, or the length of time that a patient is still alive from either the date of diagnosis or the start of treatment.

In nine studies, MRD was assessed after the completion of induction treatments, while four studies reported MRD status and the related survival outcomes after ASCT or during maintenance.

To evaluate the impact of post-induction MRD status on progression-free survival, data were extracted from nine studies involving 607 patients, including 246 who were MRD positive and 361 who were MRD negative. For the

impact of post-induction MRD status on overall survival, data were extracted from six studies involving 326 patients, including 141 who were MRD positive and 185 who were MRD negative.

Patients who were MRD positive demonstrated shorter progression-free and overall survival compared with patients who were MRD negative. Moreover, the pooled five-year progression-free survival for MRD-positive patients was 42.8%, compared with 68.9% for MRD-negative patients. Similarly, the pooled five-year overall survival rates were 63.6% and 82.3%, respectively.

To evaluate post-consolidation MRD status on progression-free survival, data were extracted from four studies involving 489 patients, including 111 who were MRD positive and 378 who were MRD negative. To evaluate post-consolidation MRD status on overall survival, data were extracted from two studies involving 210 patients, including 36 who were MRD positive and 174 who were MRD negative.

Again, positive MRD status was associated with short progression-free and overall survival, compared with those who were MRD negative.

“MRD status after both induction therapy and consolidation therapy showed prognostic value. This may provide information for deciding timing of MRD assessment. On the one hand, post-induction and post-consolidation

MRD status assessment could be useful because it has prognostic value and may provide information for further therapy decision-making,” the researchers wrote. “On the other hand, as MRD implies the depth of molecular remission, continuous assessment of MRD status can be a useful tool for monitoring early relapse.”

What You Need to Know About MRD

• MRD positive means disease was still detected after treatment.
• MRD negative means no disease was detected after treatment.
• Doctors use samples from blood or bone marrow aspiration.
• MRD can measure treatment efficacy, as well as predict patients who are at risk for relapse.
• MRD can monitor remissions or identify early return of cancer.