Letestu Rémi, Dahmani Abdelmalek, Boubaya Marouane, Baseggio Lucile, Campos Lydia, Chatelain Bernard, Debliquis Agathe, Drénou Bernard, Jacob Marie-Christine, Legac Eric, Le Garff-Tavernier Magali, Lhoumeau Anne-Catherine, Quiney Claire, Robillard Nelly, Ticchioni Michel, Aanei Carmen, Katsahian Sandrine, Delepine Roselyne, Vaudaux Sandrine, Rouillé Valérie, Béné Marie-Christine, Dartigeas Caroline, Van Den Neste Eric, Leprêtre Stéphane, Feugier Pierre, Cartron Guillaume, Leblond Véronique, Lévy Vincent, Cymbalista Florence
Laboratoire d'Hématologie, APHP CHU Avicenne, Bobigny, France.
URC, APHP CHU Avicenne, Bobigny, France.
Leukemia. 2021 Jun;35(6):1597-1609. doi: 10.1038/s41375-020-01009-z. Epub 2020 Sep 15.
Measurable residual disease (MRD) status is widely adopted in clinical trials in patients with chronic lymphocytic leukemia (CLL). Findings from FILO group trials (CLL2007FMP, CLL2007SA, CLL2010FMP) enabled investigation of the prognostic value of high-sensitivity (0.7 × 10) MRD assessment using flow cytometry, in blood (N = 401) and bone marrow (N = 339), after fludarabine, cyclophosphamide, and rituximab (FCR)-based chemoimmunotherapy in a homogeneous population with long follow-up (median 49.5 months). Addition of low-level positive MRD < 0.01% to MRD ≥ 0.01% increased the proportion of cases with positive MRD in blood by 39% and in bone marrow by 27%. Compared to low-level positive MRD < 0.01%, undetectable MRD was associated with significantly longer progression-free survival (PFS) when using blood (72.2 versus 42.7 months; hazard ratio 0.40, p = 0.0003), but not when using bone marrow. Upon further stratification, positive blood MRD at any level, compared to undetectable blood MRD, was associated with shorter PFS irrespective of clinical complete or partial remission, and a lower 5-year PFS rate irrespective of IGHV-mutated or -unmutated status (all p < 0.05). In conclusion, high-sensitivity (0.0007%) MRD assessment in blood yielded additional prognostic information beyond the current standard sensitivity (0.01%). Our approach provides a model for future determination of the optimal MRD investigative strategy for any regimen.
可测量残留病（MRD）状态在慢性淋巴细胞白血病（CLL）患者的临床试验中被广泛采用。FILO组试验（CLL2007FMP、CLL2007SA、CLL2010FMP）的结果使得能够在一组经过长期随访（中位随访时间49.5个月）的同质人群中，研究使用流式细胞术在血液（N = 401）和骨髓（N = 339）中进行高灵敏度（0.7×10）MRD评估的预后价值，这些患者接受了基于氟达拉滨、环磷酰胺和利妥昔单抗（FCR）的化学免疫疗法。将低水平阳性MRD<0.01%加入到MRD≥0.01%中，使血液中MRD阳性病例的比例增加了39%，骨髓中增加了27%。与低水平阳性MRD<0.01%相比，使用血液检测时，未检测到MRD与显著更长的无进展生存期（PFS）相关（72.2个月对42.7个月；风险比0.40，p = 0.0003），但使用骨髓检测时则不然。进一步分层后，无论临床完全缓解或部分缓解，任何水平的血液MRD阳性与未检测到血液MRD相比，均与较短的PFS相关，且无论IGHV突变或未突变状态如何，5年PFS率均较低（所有p<0.05）。总之，血液中的高灵敏度（0.0007%）MRD评估产生了超出当前标准灵敏度（0.01%）的额外预后信息。我们的方法为未来确定任何治疗方案的最佳MRD检测策略提供了一个模型。
