CLL minimal residual disease is a prognostic factor for 10-year OS and PFS

In December 2016, Marwan Kwok from the Queen Elizabeth Hospital Birmingham, UK, and colleagues published in Blood the results of a retrospective study into determining the long-term prognostic value of Minimal Residual Disease (MRD) status in CLL. The study looked at all patients between 1996 and 2007 who were treated for CLL, received a partial response or better, and had MRD assessment of bone marrow within 6 months of treatment. This resulted in 133 patients out of 536 being included in this study after exclusions.

Key Highlights:

• Treatment: 50% combination chemo-immunotherapy or chemotherapy, 19% single-agent chemotherapy, 17% chemotherapy-free treatment, 7pts ASCT (0.5%)
• MRD-negative after treatment = 41%
• Median PFS:
  • MRD-negative = 7.6 years
  • MRD at 0.001% = 3.3 years
  • MRD at >1% = 2 years
• Median OS:
  • MRD-negative = 10.6 years
  • MRD at 0.001% = 5.3 years
  • MRD at >1% = 3.6 years
• Multivariate analysis showed MRD status to be only factor significant for both PFS and OS
• Upfront MRD-negativity associated with improved 10-year PFS (65% vs 10%) and 10-year OS (70% vs 30%)
• R/R MRD-negativity associated with improved, albeit lower, 10-year PFS (30% vs 0%) and OS (47% vs 11%)

In conclusion, the authors state that, although this study did not include data from recent patients treated with modern therapies, it does support the use of MRD-negativity as a prognostic marker for long-term PFS and OS in CLL. Future long-term and prospective studies will be required to validate the prognostic significance of MRD-negativity in patients receiving modern therapies such as venetoclax.

Abstract:

Minimal residual disease (MRD) negativity, defined as <1 chronic lymphocytic leukemia (CLL) cell detectable per 10 000 leukocytes, has been shown to independently predict for clinical outcome in patients receiving combination chemoimmunotherapy in the frontline setting. However, the long-term prognostic value of MRD status in other therapeutic settings remains unclear. Here, we retrospectively analyzed, with up to 18 years follow-up, all patients at our institution who achieved at least a partial response (PR) with various therapies between 1996 and 2007, and received a bone marrow MRD assessment at the end of treatment according to the international harmonized approach. MRD negativity correlated with both progression-free survival (PFS) and overall survival (OS) in- dependent of the type and line of treatment, as well as known prognostic factors including adverse cytogenetics. The greatest impact of achieving MRD negativity was seen in patients receiving frontline treatment, with 10-year PFS of 65% vs 10% and 10-year OS of 70% vs 30% for MRD-negative vs MRD-positive patients, respectively. Our results demonstrate the long-term benefit of achieving MRD negativity, regardless of the therapeutic setting and treatment modality, and support its use as a prognostic marker for long-term PFS and as a potential therapeutic goal in CLL.