MRD assessment
| Topic . | Consensus statements . | Justification and supporting literature . |
|---|---|---|
| MRD to guide treatment | Currently, it is not standard practice to use MRD status at end of planned treatment course with Ven with the sole purpose of guiding treatment decisions. | To the best of our knowledge, although MRD-guided therapies can result in an increased proportion of patients achieving uMRD4, there is currently no evidence that this translates to improved clinical outcomes. |
| Method of MRD testing | Immunosequencing (eg, Adaptive ClonoSEQ) is the preferred MRD method based on its FDA approval for use in CLL/SLL and greater sensitivity (<10−6) and reproducibility, but a baseline sequence is required. Notably, most prospective clinical trial data have relied upon flow cytometry for MRD detection. Flow cytometry has a sensitivity for uMRD <10−4 and does not necessitate a baseline sequence and is an acceptable approach for MRD detection. | Immunosequencing is currently the preferred MRD method based on the availability of an FDA-cleared in vitro diagnostic (ClonoSEQ assay, Adaptive Biotechnologies), which renders greater sensitivity than flow cytometry. The current iwCLL definition for uMRD uses a cutoff of <10−4 (uMRD4), and flow cytometry has adequate sensitivity for uMRD4.3 Our panel acknowledges that detectable MRD <10−4 is currently of unclear significance, thus may create unnecessary worry for patients. We also acknowledge that flow cytometry is more readily available at most centers. |
| MRD testing in the peripheral blood with Ven w/wo an anti-CD20 mAb or liso-cel | Venetoclax w/wo anti-CD20 mAb: We encourage MRD testing in the peripheral blood at the end of the planned treatment course, because MRD serves as an important prognostic marker. At present, there are insufficient data to support a prognostic or predictive role of routine MRD testing at interim time points or in surveillance. Liso-cel: We encourage MRD testing in the peripheral blood at day 30 and after months 3 and 6, because MRD serves as an important prognostic marker. | Our recommendation to measure MRD in patients with CLL/SLL receiving Ven-based therapy or liso-cel is based on evidence from prospective trials demonstrating correlation between end-of-treatment MRD4 status and survival outcomes.37,38,79,95 Among previously treated patients with CLL/SLL treated with Ven and obinutuzumab, end-of-treatment uMRD4 is associated with longer PFS and OS.37,38 Among previously treated patients on Ven with rituximab, end-of-treatment uMRD4 is associated with longer PFS.79 Among previously treated patients receiving liso-cel, there is preliminary evidence that uMRD4 is associated with longer PFS.95,96 Some of us also measure MRD at an interim time point in patients receiving Ven-based therapy. This is based on MRD kinetics data from the CLL14 trial demonstrating that some patients with detectable MRD4 at end of treatment had evidence of rising MRD levels, and this provides information about potential emerging Ven resistance.37 |
| MRD testing with BTKis | MRD testing is not recommended for patients receiving continuous therapy for CLL/SLL with a BTKi. | Our recommendation against MRD testing for patients receiving continuous therapy for CLL/SLL with a BTKi is based on the lack of an association between MRD status and survival outcomes in this setting. |
| MRD testing in the bone marrow | Bone marrow biopsies obtained solely for MRD assessment are not routinely encouraged outside of clinical trials. | The peripheral blood and bone marrow demonstrate relatively high concordance (85%-90%) to detect uMRD4 with either flow cytometry or immunosequencing.80,104 Although assessing MRD in the bone marrow compartment can identify detectable MRD4 in 10%-15% of patients with uMRD4 in the peripheral blood, we find the peripheral blood MRD assessment is more practical in clinical practice. Additionally, most data linking uMRD4 and survival outcomes rely on peripheral blood MRD assessment.37,38,79,95 |
| Topic . | Consensus statements . | Justification and supporting literature . |
|---|---|---|
| MRD to guide treatment | Currently, it is not standard practice to use MRD status at end of planned treatment course with Ven with the sole purpose of guiding treatment decisions. | To the best of our knowledge, although MRD-guided therapies can result in an increased proportion of patients achieving uMRD4, there is currently no evidence that this translates to improved clinical outcomes. |
| Method of MRD testing | Immunosequencing (eg, Adaptive ClonoSEQ) is the preferred MRD method based on its FDA approval for use in CLL/SLL and greater sensitivity (<10−6) and reproducibility, but a baseline sequence is required. Notably, most prospective clinical trial data have relied upon flow cytometry for MRD detection. Flow cytometry has a sensitivity for uMRD <10−4 and does not necessitate a baseline sequence and is an acceptable approach for MRD detection. | Immunosequencing is currently the preferred MRD method based on the availability of an FDA-cleared in vitro diagnostic (ClonoSEQ assay, Adaptive Biotechnologies), which renders greater sensitivity than flow cytometry. The current iwCLL definition for uMRD uses a cutoff of <10−4 (uMRD4), and flow cytometry has adequate sensitivity for uMRD4.3 Our panel acknowledges that detectable MRD <10−4 is currently of unclear significance, thus may create unnecessary worry for patients. We also acknowledge that flow cytometry is more readily available at most centers. |
| MRD testing in the peripheral blood with Ven w/wo an anti-CD20 mAb or liso-cel | Venetoclax w/wo anti-CD20 mAb: We encourage MRD testing in the peripheral blood at the end of the planned treatment course, because MRD serves as an important prognostic marker. At present, there are insufficient data to support a prognostic or predictive role of routine MRD testing at interim time points or in surveillance. Liso-cel: We encourage MRD testing in the peripheral blood at day 30 and after months 3 and 6, because MRD serves as an important prognostic marker. | Our recommendation to measure MRD in patients with CLL/SLL receiving Ven-based therapy or liso-cel is based on evidence from prospective trials demonstrating correlation between end-of-treatment MRD4 status and survival outcomes.37,38,79,95 Among previously treated patients with CLL/SLL treated with Ven and obinutuzumab, end-of-treatment uMRD4 is associated with longer PFS and OS.37,38 Among previously treated patients on Ven with rituximab, end-of-treatment uMRD4 is associated with longer PFS.79 Among previously treated patients receiving liso-cel, there is preliminary evidence that uMRD4 is associated with longer PFS.95,96 Some of us also measure MRD at an interim time point in patients receiving Ven-based therapy. This is based on MRD kinetics data from the CLL14 trial demonstrating that some patients with detectable MRD4 at end of treatment had evidence of rising MRD levels, and this provides information about potential emerging Ven resistance.37 |
| MRD testing with BTKis | MRD testing is not recommended for patients receiving continuous therapy for CLL/SLL with a BTKi. | Our recommendation against MRD testing for patients receiving continuous therapy for CLL/SLL with a BTKi is based on the lack of an association between MRD status and survival outcomes in this setting. |
| MRD testing in the bone marrow | Bone marrow biopsies obtained solely for MRD assessment are not routinely encouraged outside of clinical trials. | The peripheral blood and bone marrow demonstrate relatively high concordance (85%-90%) to detect uMRD4 with either flow cytometry or immunosequencing.80,104 Although assessing MRD in the bone marrow compartment can identify detectable MRD4 in 10%-15% of patients with uMRD4 in the peripheral blood, we find the peripheral blood MRD assessment is more practical in clinical practice. Additionally, most data linking uMRD4 and survival outcomes rely on peripheral blood MRD assessment.37,38,79,95 |
uMRD4, undetectable minimal residual disease with cutoff of <10−4.