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A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain
Author(s) -
Tadmor Tamar,
Braester Andrei,
Najib Dally,
Aviv Ariel,
Herishanu Yair,
Yuklea Mona,
Shvidel Lev,
RahimiLevene Naomi,
Ruchlemer Rosa,
Arad Ariela,
Fogl Claudia,
Henig Clara,
Barak Mira,
Magal Lee,
Polliack Aaron,
Townsend Kelly
Publication year - 2019
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13288
Subject(s) - chronic lymphocytic leukemia , immunoglobulin light chain , medicine , leukemia , oncology , immunology , antibody
Background Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation. Aims In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment‐naïve patients with CLL. Results Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT ( P < .001). Patients with two factors represented an ultra‐high‐risk group with a median TTFT of only 1.3 months. Conclusion The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL.