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. 2023 Feb 23;12(5):1772.
doi: 10.3390/jcm12051772.

Relapsed/Refractory Chronic Lymphocytic Leukemia Patients Treated with Fixed Duration Venetoclax-Rituximab: Assessment of Response with Ultrasound, and Relationship with Minimal Residual Disease

Edoardo Benedetti  1   2 , Claudia Baratè  1 , Fabrizio Mavilia  1 , Emilia Bramanti  3 , Riccardo Morganti  4 , Valentina Guerri  1 , Giulia Cervetti  1 , Enrico Capochiani  5 , Ilaria Bertaggia  5 , Salvatore Massimo Stella  2 , Ginevra Traverso  1 , Benedetto Bruno  6 , Sara Galimberti  1
Affiliations

Relapsed/Refractory Chronic Lymphocytic Leukemia Patients Treated with Fixed Duration Venetoclax-Rituximab: Assessment of Response with Ultrasound, and Relationship with Minimal Residual Disease

Edoardo Benedetti et al. J Clin Med. .

Abstract

A fixed duration of venetoclax-rituximab (VenR) resulted in a significant benefit of both PFS and in the attainment of an undetectable minimal residual disease (uMRD) compared with bendamustine-rituximab in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients. The 2018 International Workshop on CLL guidelines, outside the context of clinical trials, suggested ultrasonography (US) as a possible imaging technique to evaluate visceral involvement, and palpation to evaluate superficial lymph nodes (SupLNs). In this real-life study we prospectively enrolled N = 22 patients. Patients were assessed by US, to determine nodal and splenic response in R/R CLL patients treated with a fixed duration VenR. We found an overall response rate, complete remission, partial remission, and stable disease, of 95.4%, 68%, 27.3%, and 4.5%, respectively. Responses were also correlated with risk categories. The time to response, and the time to clearance of the disease in the spleen, in abdominal LN (AbdLNs), and in SupLNs were discussed. Responses were independent from LN size. The correlation between response rate with MRD were also investigated. US allowed to detect a substantial CR rate correlated with uMRD.

Keywords: chronic lymphocytic leukemia; ultrasound sonography; venetoclax-rituximab.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of SupLNs achieving CR, SupLNs in persistent PR, and SupLN in SD. (A) Right axillary CLL-LN (39 mm × 24 mm) at baseline (T0). The LN appears hypoechoic, with sharp and regular borders, without a visible hilum, L/S ratio < 2, and with a thickened and reticulated cortex. (B) the same LN at T3 (27.3 mm) showing a partial involvement by CLL. The cortex appears inhomogeneous (the anterior part more thickened than the posterior part-white arrowheads, with reticulated cortex-white arrow). The hyperechoic hilum is visible, although irregular. (C) the same LN measuring 19.3 mm, has become liposclerotic (nodal CR) at T6. (D) Right axillary CLL-LN (19 mm) at T0, with round shape (L/S < 2) showing the same US features as for the LN shown in panel A. (E) the same LN at T6 showing a partial involvement by CLL (19.2 mm): US show a visible hilum which is displaced and truncated (white arrowhead 1), the cortex is thickened inhomogeneous, with reticulation (white arrow). (F) the same LN at T15 (13 mm) showing a persistent partial CLL involvement of the LN: the cortex is still not homogeneously thickened, which determines irregular borders of the LN (white arrowheads) and irregular shape of the hilum (white arrow 1) which appears dislocated in the posterior part of the LN. The cortex shows reticulation (white arrow 2). (G) left laterocervical CLL-LN in SD at T0. (H) left laterocervical CLL-LN in SD at T12. (I) Left laterocervical CLL-LN in SD at T24. The SupLNs present “chain”-shaped, contiguous, sharp borders without US visible hilum. The cortex is inhomogeneous and thickened, with reticulation.
Figure 2
Figure 2
Example of AbdLN in CR but with persistence of CLL diseased SupLN (PR) in the same patient. (A) AbdLNs (longitudinal US scan with a convex probe) at baseline (T0) (90.1 mm). (B) the same AbdLN at T3 (50.2 mm). (C) disappearance of AbdLN (CR) at T6. The abdominal aorta is shown in a longitudinal scan (white arrow) and the right and left iliac arteries are visible (white arrowheads). (D) example of a right axillary CLL-SupLN at T0 (39.2 mm); the LN has an oval shape (long axis/short axis (L/S) > 2), the cortex is thickened, inhomogeneous, and reticulated (white arrows), which determines the lobular profile of the LN (white arrowheads). (E–G) the same right axillary CLL-SupLN at T6 (39.2 mm) (E), T12 (31.4 mm) (F) and T18 (21.5 mm) (G). In panel G there is still a partial involvement by CLL: the LN has oval shape (L/S > 2), the cortex is thickened and inhomogeneous and reticulated (white arrow), and the posterior part more thickened than the anterior part). The hilum is visible but is compressed and dislocated by the thickened cortex.
Figure 3
Figure 3
Frequency distribution of patients achieving CR at different time point of US follow up.
Figure 4
Figure 4
Plot of AbdLNs and SupLNs achieving CR or still diseased, and splenic response in 22 patients examined. (A) Patients who achieve CR (AbdLNs, SupLNs and splenic CR). (B) Lymphnodal and splenic US response in patients in PR and in the patient in SD. In patients in PR, although AbdLNs and splenic response achieved a CR, SupLNs were still diseased by CLL. Patient 22 was in SD at T24 and both AbdLNs and SupLNs were still involved by CLL.
Figure 5
Figure 5
Time to response of LN< 5 cm vs. ≥ 5 cm. (A) Patients with AbdLN involvement before the initiation of treatment having LN < 5 cm reached CR at T3; patients having LN ≥ 5 cm, reached CR at T3 (N = 5 pts), at T6 (N = 2 pts), and T9 (N = 1 pts). (B) Time to CR of SupLNs < 5 cm (N = 14/15 patients) was T3 (N = 6 pts), T6 (N = 4 pts) and T12 (N = 1 pts). If SupLNs were ≥ 5 cm time to CR was T6 (N = 2 pts), and T15 (N = 1 pts).
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