Blood Neoplasia最新文献

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KIR3DL1-HLA-Bw status in CML is associated with achievement of TFR: the POKSTIC trial, a multicenter observational study CML 中的 KIR3DL1-HLA-Bw 状态与 TFR 的实现有关：多中心观察研究 POKSTIC 试验

Blood Neoplasia

Pub Date : 2024-03-01 DOI: 10.1016/j.bneo.2024.100001

Hiroshi Ureshino , Yasunori Ueda , Shin Fujisawa , Kensuke Usuki , Hideo Tanaka , Masaya Okada , Shugo Kowata , Kazunori Murai , Asao Hirose , Motohiro Shindo , Takashi Kumagai , Tomoharu Takeoka , Kazuharu Kamachi , Keisuke Kidoguchi , Takero Shindo , Satoshi Iyama , Junki Inamura , Takafumi Nakao , Tsutomu Kobayashi , Eri Kawata , Shinya Kimura

Abstract

Achievement of treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation in patients who show a durable deep molecular response (DMR) during TKI treatment of chronic myeloid leukemia in chronic phase (CML-CP) is a therapeutic goal; however, the prognostic factors that predict successful achievement of TFR are unclear. Previously, we reported that killer immunoglobulin-like receptor (KIR) and HLA polymorphisms are associated with achievement of a DMR. Here, we investigated the association between KIR and HLA polymorphisms and TFR. We conducted the POKSTIC (POlymorphisms of Killer immunoglobulin-like receptor, which affect Stop Tyrosine kinase Inhibitor in patients with Chronic myeloid leukemia) trial, a multicenter collaborative observational study that enrolled 76 patients with CML-CP. The median age was 63 years (interquartile range [IQR], 49-70). Of 76 patients, 42 (56.6%; 95% confidence interval [CI], 47.7-66.8 at 6 months) discontinued TKIs without molecular relapse; the median follow-up time for TFR was 24 months (IQR, 16-64). KIR genotyping and allele typing did not identify risk factors for molecular relapse; however, univariate and multivariate analysis identified the combination of KIR3DL1-HLA-Bw4 (an HLA-B allele) as an independent factor for a higher risk of molecular relapse (hazard ratio, 2.206; 95% CI, 1.112-4.376; P = .024). Notably, patients at higher risk of relapse had a significantly lower number of natural killer (NK) cells at TKI discontinuation than the other patients (CD16⁺/CD56⁺ NK cells: median 499.63 cells per μL vs 629.17 cells per μL, respectively; P = .049). Thus, KIR3DL1-HLA-Bw status reflects NK cell responses and is associated with TFR. The study is registered with the UMIN Clinical Trials Registry as #UMIN000041798.

摘要在酪氨酸激酶抑制剂（TKI）治疗慢性期髓性白血病（CML-CP）期间出现持久深度分子反应（DMR）的患者停用TKI后实现无治疗缓解（TFR）是一项治疗目标；然而，预测成功实现TFR的预后因素尚不清楚。以前，我们曾报道过杀伤性免疫球蛋白样受体（KIR）和 HLA 多态性与 DMR 的实现有关。在此，我们研究了 KIR 和 HLA 多态性与 TFR 之间的关联。我们开展了 POKSTIC（影响慢性髓性白血病患者酪氨酸激酶抑制剂停药的杀手免疫球蛋白样受体多态性）试验，这是一项多中心合作观察性研究，共招募了 76 名 CML-CP 患者。中位年龄为 63 岁（四分位数间距 [IQR]，49-70）。76 名患者中，42 人（56.6%；95% 置信区间 [CI]，47.7-66.8，6 个月）停用 TKIs 后未出现分子复发；TFR 的中位随访时间为 24 个月（IQR，16-64）。KIR 基因分型和等位基因分型并未发现分子复发的风险因素；但单变量和多变量分析发现，KIR3DL1-HLA-Bw4（HLA-B 等位基因）组合是分子复发风险较高的独立因素（危险比为 2.206；95% CI 为 1.112-4.376；P = .024）。值得注意的是，复发风险较高的患者在停用 TKI 时的自然杀伤（NK）细胞数量明显低于其他患者（CD16+/CD56+ NK 细胞：中位数分别为 499.63 cells per μL vs 629.17 cells per μL；P = .049）。因此，KIR3DL1-HLA-Bw 状态反映了 NK 细胞反应并与 TFR 相关。该研究已在 UMIN 临床试验注册中心注册，注册号为 #UMIN000041798。

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引用次数: 0

Real-world comparison of daratumumab-based regimens in relapsed/refractory multiple myeloma using health record data 利用健康记录数据对基于达拉单抗的复发性/难治性多发性骨髓瘤治疗方案进行真实世界比较

Blood Neoplasia

Pub Date : 2024-03-01 DOI: 10.1016/j.bneo.2024.100003

Benjamin A. Derman , Jacob Ambrose , Laura L. Fernandes , Christina M. Zettler , Eric Hansen , Andrew J. Belli , Ching-Kun Wang

Abstract

Daratumumab (dara)-based triplet therapies are commonly used in the second-line (2L) and third-line (3L) settings in relapsed/refractory multiple myeloma (RRMM), usually in combination with dexamethasone and either bortezomib (dara-Vd), carfilzomib (dara-Kd), or pomalidomide (dara-Pd). We performed a real-world (rw) analysis to directly compare these regimens, to our knowledge, for the first time. This was an observational, retrospective cohort study using COTA’s rw database of patients with MM who have initiated 2L or 3L therapy with dara-Vd, dara-Kd, or dara-Pd. rw time to next treatment (rwTTNT) and rw overall survival (rwOS) were analyzed using the Kaplan-Meier method. Comparative analyses were conducted using a trimmed inverse probability of treatment weighting method to control for potential confounders. A total of 639 patients received a dara-based regimen as either 2L or 3L therapy (dara-Vd, n = 201; dara-Kd, n = 122; and dara-Pd, n = 316). A high proportion had functional (52%) or cytogenetic (26%) high-risk disease; 49% were lenalidomide refractory. Median rwTTNT for dara-Vd was 7.6 months and was 12.9 months for dara-Kd (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.49-0.99). Similarly, median rwTTNT for dara-Vd was 6.9 months and 15.3 months for dara-Pd (HR, 0.57; 95% CI, 0.43-0.77). Median rwTTNT for dara-Pd was 15.7 months, and for dara-Kd 13.2 months (HR, 1.1; 95% CI, 0.8-1.6). No regimen was associated with superior rwOS. Among patients with RRMM receiving 2L or 3L therapy with a dara-based triplet, dara-Vd was associated with inferior rwTTNT compared with both dara-Kd and dara-Pd. dara-Vd may not be a suitable control arm for most phase 3 studies.

摘要基于达拉单抗（dara）的三联疗法常用于复发性/难治性多发性骨髓瘤（RRMM）的二线（2L）和三线（3L）治疗，通常与地塞米松和硼替佐米（dara-Vd）、卡非佐米（dara-Kd）或泊马度胺（dara-Pd）联合使用。据我们所知，我们首次进行了真实世界（rw）分析，以直接比较这些治疗方案。这是一项观察性、回顾性队列研究，使用的是 COTA 的 rw 数据库，研究对象是使用 dara-Vd、dara-Kd 或 dara-Pd 开始 2L 或 3L 治疗的 MM 患者。采用 Kaplan-Meier 法分析了 rw 下次治疗时间 (rwTTNT) 和 rw 总生存期 (rwOS)。比较分析采用修剪的逆治疗概率加权法，以控制潜在的混杂因素。共有639名患者接受了以达拉为基础的2L或3L治疗方案（达拉-Vd，n = 201；达拉-Kd，n = 122；达拉-Pd，n = 316）。高比例患者患有功能性（52%）或细胞遗传学（26%）高危疾病；49%为来那度胺难治性患者。dara-Vd 的中位 rwTTNT 为 7.6 个月，dara-Kd 为 12.9 个月（危险比 [HR]，0.70；95% 置信区间 [CI]，0.49-0.99）。同样，达拉-Vd 的中位 rwTTNT 为 6.9 个月，达拉-Pd 为 15.3 个月（HR，0.57；95% CI，0.43-0.77）。dara-Pd 的中位 rwTTNT 为 15.7 个月，dara-Kd 为 13.2 个月（HR，1.1；95% CI，0.8-1.6）。没有一种方案的rwOS更优。在接受2L或3L达拉三联疗法的RRMM患者中，与达拉-Kd和达拉-Pd相比，达拉-Vd的rwTTNT较差。

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引用次数: 0

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Blood Neoplasia

Pub Date : 2024-02-15 DOI: 10.1016/j.bneo.2024.100006

Agnes Mattsson , Jeanette Lundin , Tom A. Mulder , Sandra E. Sylvan , Marzia Palma , Lotta Hansson ∗ , Anders Österborg ∗

引用次数: 0

Multiple myeloma-associated DIS3 gene is essential for hematopoiesis but loss of DIS3 is insufficient for myelomagenesis 多发性骨髓瘤相关 DIS3 基因对造血至关重要，但 DIS3 基因缺失不足以导致骨髓瘤形成

Blood Neoplasia

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Hiroto Ohguchi, Yasuyo Ohguchi, Sho Kubota, Kan Etoh, Ai Hamashima, Shingo Usuki, Takako Yokomizo-Nakano, Jie Bai, Takeshi Masuda, Y. Kawano, Takeshi Harada, Mitsuyoshi Nakao, Takashi Minami, T. Hideshima, Kimi Araki, G. Sashida

引用次数: 0

Castleman disease patients report mild COVID-19 symptoms and mount a humoral response to SARS-CoV-2 vaccination 卡斯特曼病患者出现轻微的 COVID-19 症状，并对接种 SARS-CoV-2 疫苗产生体液反应

Blood Neoplasia

Pub Date : 2024-02-01 DOI: 10.1016/j.bneo.2024.100002

S. Shyamsundar, S. Pierson, C. Connolly, M. Teles, D. Segev, W. Werbel, F. van Rhee, Corey Casper, Joshua D. Brandstadter, Ariela Noy, D. Fajgenbaum

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Frequent response monitoring in chronic lymphocytic leukemia clinical trials: what is the value? 慢性淋巴细胞白血病临床试验中的频繁反应监测：价值何在？

Blood Neoplasia

Pub Date : 2024-02-01 DOI: 10.1016/j.bneo.2024.100006

Agnes Mattsson, J. Lundin, T. Mulder, S. E. Sylvan, M. Palma, L. Hansson, Anders Österborg

引用次数: 0

Real-world Comparison of Daratumumab-Based Regimens in Relapsed/Refractory Multiple Myeloma Using Health Record Data 利用健康记录数据对基于达拉单抗的复发性/难治性多发性骨髓瘤治疗方案进行真实世界比较

Blood Neoplasia

Pub Date : 2024-02-01 DOI: 10.1016/j.bneo.2024.100003

B. Derman, J. Ambrose, L. Fernandes, C. Zettler, E. Hansen, A. Belli, Ching-Kun Wang

引用次数: 0

KIR3DL1-HLA-Bw status in CML is associated with achievement of TFR: the POKSTIC Trial, a Multicentre Observational Study CML 中的 KIR3DL1-HLA-Bw 状态与 TFR 的实现有关：多中心观察研究 POKSTIC 试验

Blood Neoplasia

Pub Date : 2024-02-01 DOI: 10.1016/j.bneo.2024.100001

H. Ureshino, Yasunori Ueda, Shin Fujisawa, Kensuke Usuki, Hideo Tanaka, Masaya Okada, S. Kowata, Kazunori Murai, Asao Hirose, Motohiro Shindo, Takashi Kumagai, Tomoharu Takeoka, K. Kamachi, K. Kidoguchi, T. Shindo, Satoshi Iyama, J. Inamura, Takafumi Nakao, Tsutomu Kobayashi, E. Kawata, H. Ohkawara, Takayuki Ikezoe, Atsushi Kawaguchi, Shinya Kimura

引用次数: 0

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