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ACE-LY-003 Phase II trial results update: aclotinib has shown good efficacy and safety in relapsed/refractory marginal zone lymphoma

 Last Update: 2022-11-04
 Source: Internet
 Author: User

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oclacitinib 16 mg

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Marginal zone lymphoma (MZL) is an indolent B-cell malignancy that accounts for about 7%
of B-cell non-Hodgkin lymphoma (B-NHL).
First-line therapy for MZL with high tumour burden is usually chemoimmunotherapy
.
However, the treatment of relapsed/refractory MZL (R/R MZL), especially R/R MZL, which is not suitable for chemoimmunotherapy, is very limited
.
Acalabrutinib is a BTK inhibitor that has shown good efficacy and safety
in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and relapsed/refractory mantle cell lymphoma (R/R MCL).
Preclinical studies have shown that aclotinib + PI3K inhibitors have antitumor activity
in several aggressive lymphoma and MZL cell lines.
In order to further explore the efficacy and safety of aclotinib in MZL, Paolo Strati et al.
from the United States conducted a phase II proof-of-concept study to explore the efficacy and safety
of aclotinib monotherapy in R/R MZL.

01 Study method
patient inclusion criteria include: (1) age≥ 18 years old; (2) Histologically diagnosed with spleen, lymph nodes or extralymph node MZL; (3) Have measurable lesions, defined as the presence of at least one lesion, measured by CT, the longest diameter of the lesion is ≥ 2cm, and the longest vertical length is ≥ 1cm; (4) ECOG score 0-2; (5) Prior ≥ 1-line therapy (including at least one CD20-targeted therapy).

Bone marrow aspiration and/or biopsy
is performed 90 days before the first dose of acrotinib or at enrollment.
For tumor evaluation, pre-treatment CT scan is performed within 30 days before the first dose of acrotinib and PET/CT is performed within 60 days before treatment as a control
.
Patients with gastric mucosa-associated lymphoma require endoscopy at enrollment or within 90 days of the first dose of acrotinib
.
CT scans are performed every 3 cycles (12 weeks, ± 7 days) starting on day 1 of the 4th, 7th, and 10th 13 treatment cycles, and every 24 weeks thereafter, or adjust the frequency
of CT scans at the discretion of the investigator.
The primary endpoint was overall response rate (ORR), secondary endpoints were duration of response (DOR), progression-free survival (PFS), and safety, and exploratory endpoints were minimal residual disease (MRD)
negativity.

02Research results

Baseline characteristics of the patient

As of January 4, 2022, a total of 43 patients with R/R MZL received aclotinib monotherapy (100 mg BID until disease progression or intolerable toxicity).

The median age of the patient was 69 years (range: 42-84), and the baseline characteristics of the patient are shown in Table 1
.

Table 1 Baseline characteristics of patients

efficacy

At a median follow-up of 13.
3 months (range 0.
5-45.
5), the ORR of 40 patients with evaluable efficacy was 52.
5% (95% CI 36.
1%–68.
5%) (n=21), the rate of complete response (CR) was 12.
5% (n=5), and the rate of partial response (PR) was 40.
0% (n=16) (Table 2).

The median to initial response time was 2.
9 months, the median to optimal response time was 3.
0 months, and the median DOR was not achieved (95% CI 8.
4 months-NR) (Table 2, Figure 1).

Table 2 Treatment response of patients that can be evaluatedFigure 1 The patient DOR curve
Among the 21 patients who responded to treatment, 6 hematological MRDs could be evaluated, including 2 CR and 4 PR.

Two of the 6 patients achieved MRD-negative (<1^×10-4) during treatment, and all were PR patients
.
After a median follow-up of 13.
3 months, the median PFS was estimated to be 27.
4 months (95% CI 11.
1 months -NR) and the 12-month PFS rate was 67.
0% (95% CI 46.
4% to 81.
1%) (Figure 2A).

Median overall survival (OS) was not achieved, and the 12-month OS rate was 91.
4% (95% CI 75.
6%–97.
1%) (Figure 2B).

security

Ninety-five percent of patients experienced at least one adverse event (TEAE) that occurred during treatment, most TEAE were grade 1 to 2, and 17 patients developed grade 3 TEAE ≥ (Table 3).

Thirteen patients (30%) had to be discontinued for TEAE and 3 patients (7%) discontinued aclotinib
for TEAE.

Table 3 TEAE in patients Among the clinically significant TEAE
, 2 patients (5%) reported grade 2 hypertension, 1 had a history of hypertension, worsened with aclotinib treatment, and 1 had no history of
hypertension.
Six patients (14%) developed any grade of neutropenia, one of whom was interfected
.
Of the patients who developed neutropenia, 1 had a dose adjustment
due to neutropenia.
Two patients developed secondary primary malignancy
.
One patient had grade 3 drug-induced pneumonia that resolved
approximately 40 days after discontinuation.
No patients developed atrial fibrillation/flutter
.

03 Study ConclusionThe
preliminary report of this phase II trial shows that aclotinib has good
efficacy and tolerability in R/R MZL.
Aclotinib can be used as a safe alternative for patients with R/R MZL and as an option without
chemotherapy.
However, this study was small and had a short median follow-up, and larger studies with longer follow-up are needed in the future to further clarify the potential role
of aclotinib in R/R MZL.

Reference sources: Strati P, Coleman M, Champion R, et al.
A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma.
Br J Haematol.
2022; 199(1): 76– 85.
https://doi.
org/10.
1111/bjh.
18368.
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