Measurable residual disease: predictor of mantle cell lymphoma outcome

Residual disease (MRD) status that can be measured after treatment in peripheral blood and bone marrow correlates
with clinical outcomes in patients with B-cell lymphoma.
To prospectively evaluate the predictive value of this biomarker in mantle cell lymphoma (MCL), Italian investigators conducted a multicenter, randomized, phase 3 trial of 300 previously untreated MCL patients who received rituximab + chemotherapy induction therapy, followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT).

Patients were then randomly assigned to receive lenalidomide maintenance therapy or observation for 24 months
.

Peripheral blood and bone marrow samples
are collected at multiple predetermined time points during each treatment phase, as well as every 6 months during and after maintenance therapy.
MRD analysis was performed using real-time qualitative (RQ) PCR and nested PCR to detect immunoglobulin sites and CCND1(BCL1)/IgH translocation breakpoints
.
The effect
of MRD positivity on time to progression was determined by obtaining each MRD result to time to disease progression or death.

Of the 300 patients, 250 (83%) had MRD markers available
.
RQ-PCR results are more predictive than nested PCR results
.
MRD analysis was the most predictive of outcomes six months after completion of ASCT
.
Bone marrow results are more predictive than peripheral blood results at early time points of treatment, but at later time points, peripheral blood results are reliable and recommended for long-term monitoring
.

These results prospectively confirm that MRD is a highly sensitive biomarker of disease progression and outcome in patients with MCL
.
As noted by the authors and review contributors, MRD status and response dynamics provide tools to adjust treatment options based on risk, including decisions about regimen de-escalation, preemptive treatment when MRD transitions from negative to positive, and initiation of alternative regimens
for populations at high risk of early progression.
Several MRD-based studies are underway that are more sensitive and already used in clinical next-generation sequencing methods
.

Articles that were commented on

Ferrero S et al.
Punctual and kinetic MRD analysis from the Fondazione Italiana Linfomi MCL0208 phase 3 trial in mantle cell lymphoma.
Blood 2022 Sep 22; 140:1378.
(https://doi.
org/10.
1182/blood.
2021014270)

Blombery P and Cheah CY.
Predicting the future in MCL with MRD.
 Blood 2022 Sep 22; 140:1332.
(https://doi.
org/10.
1182/blood.
2022017278)