Table 3.

First applications of next-generation technologies to molecular monitoring in FL

Study	Patients	Marker/tissue/timing	Method	Potential impact
Genuardi et al38	20 FL with no MBR or mcr	BCL2/TLA BM At diagnosis and for MRD	TLA	BCL2/TLA in 8 (40%) of “marker-negative” cases The new BCL2/TLA markers were suitable for RQ-PCR MRD analysis in 4 of 5 cases. MRD by BCL2-TLA reached good sensitivity levels.
Cavalli et al40	67 early stage FL	BCL2/IGH PB, BM At diagnosis and for MRD	ddPCR	Concordance between ddPCR and RQ-PCR: 82% ddPCR identified a MBR marker in 8 of 18 (44%) samples that resulted in MBR−/mcr− by qualitative nested PCR. Molecular tumor burden at diagnosis ≥10−5 significantly predicted PFS only when quantified by ddPCR but not by RQ-PCR. Higher sensitivity of ddPCR in RQ-PCR PNQ samples.
Sarkozy et al42	34 FL from PRIMA trial	IGH Tumor biopsy Plasma At diagnosis	NGS	29 (85%) had 1 or more tumor clonotypes in the tumor biopsy specimen. 25 (74%) had 1 or more tumor clonotypes in plasma. 18 of 24 (75%) patients with an IGH clonotype had several detectable subclones in the tumor or in the plasma. 13 of 24 (54%) showed a subclone detected in both the plasma and the tumor. >50% of cases showed a different distribution of subclones between tumor and plasma. High ctDNA levels at diagnosis predicted short PFS in MVA.
Delfau-Larue et al43	FL	PET TMTV (n = 133) BCL2/IGH PB CTC (n = 68) PB cfDNA (n = 61) At diagnosis	ddPCR	23 of 68 cfDNA were BCL2/IGH+ (ctDNA ≤10% cfDNA). High correlation between CTCs and TMTV and between cfDNA and TMTV CTCs predictive of outcome in univariate analysis but not in MVA Total cfDNA levels and TMTM are independent predictors of outcome.

CTC, circulating tumor cell; PNQ, positive not quantifiable; TMTV, total metabolic tumor volume.