Gambacorti-Passerini Carlo, Chen Clara, Davis Catherine, Sen Ginny P, Guyan Christy, Hehlmann Rüdiger, Michallet Mauricette, Paquette Ronald, Goldberg Stuart L
University of Milano Bicocca, San Gerardo Hospital, Monza, Italy.
Bristol-Myers Squibb, Princeton, NJ, USA.
Eur J Haematol. 2021 Jan;106(1):82-89. doi: 10.1111/ejh.13524. Epub 2020 Oct 9.
SIMPLICITY (NCT01244750) is an observational study of patients with chronic-phase chronic myeloid leukemia (CP-CML) in routine clinical practice receiving first-line tyrosine kinase inhibitors (TKIs). We evaluated TKI treatment changes and how switching affects clinical response in patients recruited in Europe with ≥3 years of follow-up.
The SIMPLICITY European cohort (France, Germany, Italy, the Netherlands, Russia, and Spain) included 431 patients. 370 (86%) were followed for ≥3 years.
Proportions of patients experiencing treatment interruptions, TKI switching, and discontinuations decreased over 3 years' follow-up. Intolerance was a key driver for treatment changes. Complete cytogenetic response (CCyR) was achieved in 87.5% of patients switching TKI within 3 years of initiation vs 91.7% of non-switchers. Major molecular response (MMR) was achieved in 82.4% of switchers vs 92.9% of non-switchers. Over 3 years, not switching TKI was a strong predictor for achieving CCyR or MMR (both P < .05). Three-year survival remained high, irrespective of treatment changes (95.3% switchers, 96.4% non-switchers).
European patients with CP-CML who do not switch TKI are more likely to achieve clinical response, while intolerance is a key driver for switching. Successful CML management may require careful selection of initial TKI, with early monitoring of response and intolerance.
SIMPLICITY(NCT01244750)是一项针对慢性期慢性髓性白血病(CP-CML)患者的观察性研究,这些患者在常规临床实践中接受一线酪氨酸激酶抑制剂(TKI)治疗。我们评估了TKI治疗的变化以及换药如何影响在欧洲招募的随访时间≥3年的患者的临床反应。
SIMPLICITY欧洲队列(法国、德国、意大利、荷兰、俄罗斯和西班牙)包括431例患者。370例(86%)患者接受了≥3年的随访。
在3年的随访期间,经历治疗中断、换药和停药的患者比例下降。不耐受是治疗变化的关键驱动因素。在开始治疗3年内换药的患者中,87.5%实现了完全细胞遗传学缓解(CCyR),而未换药的患者中这一比例为91.7%。换药患者中82.4%实现了主要分子学缓解(MMR),未换药患者中这一比例为92.9%。在3年期间,不换药是实现CCyR或MMR的有力预测因素(两者P均<0.05)。无论治疗变化如何,3年生存率均保持在较高水平(换药者为95.3%,未换药者为96.4%)。
未更换TKI的欧洲CP-CML患者更有可能实现临床反应,而不耐受是换药的关键驱动因素。成功管理CML可能需要谨慎选择初始TKI,并早期监测反应和不耐受情况。