Long-term follow-up confirmed that Venecla and rituximab have an excellent effect in the treatment of R/R CLL patients for a fixed period of time

When newly treated chronic lymphocytic leukemia (CLL) achieves deep remission after immunochemotherapy (CIT) and minimal residual disease (uMRD) is undetectable, progression-free survival (PFS) usually occurs without continuous treatment Extension
.

However, for patients with relapsed/refractory CLL (R/R CLL), the proportion of patients with deep remission after CIT decreased significantly
.

The application of small molecule targeted drugs, such as BCR signaling pathway inhibitors (BTK inhibitors), has changed the initial treatment and the treatment mode of R/R CLL
.

Although BTK inhibitors can achieve partial remission (PR) in most patients, they require continuous treatment
.

Therefore, new targeted therapies are needed to achieve long-lasting deep remission for newly treated or R/R CLL patients without the need for continuous treatment
.

Venecla is a BCL-2 inhibitor that kills CLL cells by inducing apoptosis
.

The latest research results show that the complete remission (CR) rate of veneclax combined with rituximab is 51%, the bone marrow uMRD rate is 57%, and the 2-year PFS rate is 82%; and it can be used in non-continuous treatment mode Allow patients to achieve long-lasting deep relief
.

Continuous treatment in a fixed cycle can minimize the side effects associated with treatment and the costs associated with continuous treatment
.

Recently, a researcher reported the long-term efficacy and safety analysis of the clinical study of Venecla combined with rituximab in the treatment of CLL
.

01 Research Method The clinical study is a phase Ib open, multi-center, dose escalation and cohort expansion trial, enrolling patients with R/R CLL from August 6, 2012 to May 28, 2014
.

The patients first received the treatment of venexan combined with rituximab, and the patients who reached CR (regardless of the MRD status) or PR with uMRD continued to use venexan or stopped the treatment
.

02 Study results Patient demographic characteristics and treatment distribution A total of 49 patients were enrolled in this study
.
The key demographic and clinical characteristics have been reported in previous reports .

The median age was 68 years, and the median number of patients' previous treatment was 2 (range: 1-5 lines)
.

As of June 4, 2019, the median study time was 5.
3 years, and the median time to receive Venecla treatment was 2.
5 years
.

The overall response rate (ORR) of patients in the overall study population was 86% (95% CI: 73%-94%), and 53% of patients reached CR/CRi with incomplete recovery of blood counts.
Within 1 year, 1 The proportion of patients who achieved CR/CRi for the first time within 2 years and 2 years later was 29%, 16% and 8%, respectively
.

The median overall survival (OS) of patients was not reached.
The 5-year OS rate was 86% (95% CI: 72%-94%); the 5-year PFS rate was 56% (95% CI: 40%-70%).
The estimated median PFS is 5.
6 years (95% CI: 3.
1-6.
6) (Figure 1)
.

Among 42 patients who achieved remission, the 5-year sustained remission rate was 58% (95% CI: 40%-73%), and the estimated median duration of remission (DOR) was 6.
2 years (95% CI: 3.
9- 6.
3)
.

Further analysis showed that the 5-year sustained remission rate of patients who reached uMRD at 12 months was 71% (95% CI: 43%-87%), while 44 patients did not reach uMRD at 12 months or at any time during the study period.
% (95% CI: 21%-65%)
.

Figure 1: Kaplan-Meier analysis of OS and PFS in all patients.
Overall prognosis of patients with deep remission.
A total of 33 patients (67%) in the study achieved CR and/or uMRD.
According to the decision of the patient/investigator, 14 patients chose to continue After receiving Venecla monotherapy (continuous treatment), 19 patients stopped Venecla treatment (fixed-period continuous treatment) after a median of 1.
4 years and continued to participate in the study
.

The median follow-up time was about 5.
5 years, the 5-year PFS rate was 79%, and the estimated median was 6.
5 years
.

Patients who received deep remission (CR and/or uMRD) who continued to use Venecla therapy.
Among the 14 patients who received continuous Venecla treatment who achieved deep remission, 8 patients were still undergoing treatment, and 2 patients continued to remission After the drug was discontinued, 4 patients developed disease progression, 3 of them withdrew from the study, 1 case is still under study, changing the treatment mode (increasing the dose of veneclax to 600 mg per day, and combining with rituximab in the second cycle Monoclonal antibody) after the disease is controlled
.

The median duration of Venecla treatment for these patients was 5.
6 years, the 5-year PFS rate was 79%, and the estimated median PFS was 6.
6 years
.

The 5-year sustained remission rate and the estimated median DOR were 71% and 6.
3 years, respectively
.

Patients who discontinued Venecla treatment after achieving deep remission (CR and/or uMRD) had a median time of first using Venecla treatment of 1.
4 years, and the median time of Venecla treatment including retreatment was 2.
1 years
.

So far, the median study time is 5.
4 years, and the median discontinuation time is 3.
2 years
.

The 5-year PFS rate for these patients was 80%, and the estimated median PFS was 6.
5 years (Figure 2)
.

The 5-year sustained response rate and estimated median DOR of these patients were 79% and 6.
2 years, respectively (Figure 3)
.

Six of the 19 patients who discontinued treatment and achieved deep remission developed disease progression, and the median time from treatment discontinuation to progression was 3.
4 years
.

As of the data cut-off date, 4 patients received veneclax and rituximab again
.

Figure 2: PFS of patients with continuous treatment and fixed cycle treatment after obtaining deep remission Figure 3: DOR to venexa treatment failure time (TTVF) for patients with continuous treatment and fixed cycle treatment after obtaining deep remission for retreatment of venacola after progression Of patients, the TTVF of patients who achieved uMRD or CR was evaluated
.

Among patients with deep remission, the failure rate of 5-year treatment without venecola was 93% in the fixed-cycle treatment group and 79% in the continuous treatment group
.

Safety The most common "treatment period" adverse events (TEAE) in all patients included upper respiratory tract infections, diarrhea, and neutropenia
.

No new toxicity was reported after 2 years of treatment
.

The only TEAEs of any grade reported by ≥20% of patients were upper respiratory tract infection, neutropenia, diarrhea, and nausea
.

The only grade 3/4 TEAEs reported by ≥10% of patients were neutropenia and leukopenia
.

03 Research conclusions The results of long-term follow-up for more than 5 years showed that the fixed-cycle continuous treatment and continuous treatment of Veneclair combined with rituximab have similar effectiveness and durability of remission for CLL patients
.

References: Shuo Ma, John F Seymour, Danielle M Brander, et al.
Efficacy of venetoclax plus rituximab for relapsed CLL: 5-year follow-up of continuous or limited- duration therapy.
Blood.
2021 Sep 9;138(10) :836-846.
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