Fadaos Nashwa, Dor Yossi Ben, Azoulay Tehila, Leiba Ronit, Sharon-Horesh Nurit, Levi Tsofia, Horowitz Netanel A, Tzoran Inna, Lavi Noa, Beyar-Katz Ofrat, Dann Eldad J, Zuckerman Tsila, Ringelstein-Harlev Shimrit
The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Hematology Laboratory, Rambam Health Care Campus, Haifa, Israel.
Ann Hematol. 2024 Dec;103(12):5861-5870. doi: 10.1007/s00277-024-06130-y. Epub 2024 Dec 12.
The prevalence of anti-CD20 monoclonal antibody (MoAb)-associated delayed-onset neutropenia (DON) varies between 8 and 27%. Despite the wide use of MoAbs as maintenance in follicular lymphoma (FL), data regarding DON occurrence and clinical consequences are limited. This study assessed DON prevalence, severity and risk factors in FL patients during maintenance. Data were retrieved from electronic medical records of FL patients treated at Rambam between 2006 and 2021. The maintenance cohort included 155 patients receiving 165 treatment courses; the non-maintenance cohort included 58 patients receiving 67 courses. Median time on maintenance was 1.81 ± 0.28 years. During maintenance, 23.2% of patients developed DON, with 13.8% experiencing at least one recurrent event. In the non-maintenance cohort, 29.3% developed DON, with 38.8% recurrence. Median time from maintenance initiation to the first neutropenic episode was 5 (1.25-12) months, whereas in the non-maintenance cohort, DON occurred earlier [1.9 (0.97-3.71) months; p = 0.06]. The only DON risk factors in patients on maintenance were induction with the obinutuzumab/bendamustine combination [odds ratio (OR): 4.546 (95%CI = 1.419-14.563); p = 0.011] or obinutuzumab maintenance [OR: 3.138 (95%CI = 1.23-7.94); p = 0.016]. In the non-maintenance cohort, such factors included ≥ 1 line of therapy [OR: 3.93 (95%CI = 1.00-15.38); p = 0.04] and a lower absolute neutrophil count at induction completion. Differences in the likelihood of DON development between patients receiving maintenance with obinutuzumab or rituximab possibly reflect mechanistic dissimilarities between type I and type II MoAbs. Regardless, prolonged MoAb use bears a mitigatory effect, reducing recurrence of DON. The findings obtained could assist in predicting the risk of DON in individual FL patients, optimizing informed treatment choices.
抗CD20单克隆抗体（MoAb）相关迟发性中性粒细胞减少症（DON）的发生率在8%至27%之间。尽管MoAbs在滤泡性淋巴瘤（FL）维持治疗中广泛应用，但关于DON发生情况及临床后果的数据有限。本研究评估了FL患者维持治疗期间DON的发生率、严重程度及危险因素。数据取自2006年至2021年在兰巴姆接受治疗的FL患者的电子病历。维持治疗队列包括155例接受165个疗程治疗的患者；非维持治疗队列包括58例接受67个疗程治疗的患者。维持治疗的中位时间为1.81±0.28年。维持治疗期间，23.2%的患者发生DON，其中13.8%经历至少一次复发事件。在非维持治疗队列中，29.3%的患者发生DON，复发率为38.8%。从开始维持治疗到首次出现中性粒细胞减少发作的中位时间为5（1.25 - 12）个月，而在非维持治疗队列中，DON出现得更早[1.9（0.97 - 3.71）个月；p = 0.06]。维持治疗患者中唯一的DON危险因素是使用奥妥珠单抗/苯达莫司汀联合诱导治疗[比值比（OR）：4.546（95%CI = 1.419 - 14.563）；p = 0.011]或奥妥珠单抗维持治疗[OR：3.138（95%CI = 1.23 - 7.94）；p = 0.016]。在非维持治疗队列中，此类因素包括≥1线治疗[OR：3.93（95%CI = 1.00 - 15.38）；p = 0.04]以及诱导治疗结束时较低的绝对中性粒细胞计数。接受奥妥珠单抗或利妥昔单抗维持治疗的患者发生DON可能性的差异可能反映了I型和II型MoAbs之间的机制差异。无论如何，延长MoAb使用具有缓解作用，可降低DON的复发率。所得结果有助于预测个体FL患者发生DON的风险，优化明智的治疗选择。
