Real-world study results of Venecla in the treatment of patients with relapsed and refractory multiple myeloma

Background In recent years, with the application of new drugs including proteasome inhibitors (PI) and immunomodulators (IMiD), the remission rate and survival of patients with multiple myeloma (MM) have been significantly improved
.

The second-generation PI and IMiD, as well as monoclonal antibodies and antibody-drug conjugates (ADC) have made continuous progress in the treatment of MM, but there is still no cure for the disease
.

Venecla is a BCL-2 inhibitor, in MM especially patients with t(11;14), it has shown impressive clinical activity as a monotherapy and in combination with other drugs
.

Although the results of early clinical trials are encouraging, the treatment of MM patients with t(11;14) in combination with veneclair and bortezomib and dexamethasone increases the remission rate to 67%, but the patients receiving treatment have clinical outcomes Data is limited
.

Based on this, some researchers have evaluated the real-world curative effect of Venecla in relapsed or refractory MM (R/R MM)
.

Research Method The study included patients with R/R MM who were treated at the Mayo Clinic in Rochester from December 2016 to March 2019 and were treated with a Venecla-containing regimen outside of the clinical trial
.

The patients are staged according to the International Staging System (ISS) of MM
.

According to International Myeloma Working Group (IMWG) standards, high-risk cytogenetic abnormalities are classified, including t(4;14), 17p-, t(14;16), t(14;20) and 1q21+
.

The data deadline is August 6, 2020
.

Study Results 1 Baseline characteristics of patients The study included 56 patients with R/R MM who were treated with Venecla.
The baseline characteristics are shown in Table 1
.

Forty-two patients (75%) had t(11;14) detected by fluorescence in situ hybridization (FISH), and 38% had high-risk cytogenetic abnormalities
.

The expression of BCL-2 in 30 patients can be assessed by immunohistochemistry.
Among them, 18 cases (60%) with strong expression and 5 cases (17%) with weak expression, patients with strong expression of BCL-2 more often have t(11;14).
See Table 2
.

The median number of previous treatment lines for patients was 6, and 14% of patients had received more than 10 lines of previous treatment
.

79% of patients had previously received autologous hematopoietic stem cell transplantation (ASCT), and 61% of patients were five-fold refractory
.

The median time from the diagnosis of MM to the start of Veneclair treatment was 4.
6 years
.

Table 1: Patient baseline characteristics Table 2: Whether the patient has t(11;14) and BCL2 expression status 2 Patient treatment status 55% of patients in this study were treated with venexa monotherapy or dual therapy combined with dexamethasone ; 45% of patients use triple or quadruple therapy.
The triple therapy plan combines Venecla with PI (bortezomib, carfilzomib or ixazomib) or daratumomab combined with dexamethasone, quadruple The regimen is venezola, daratumomab, bortezomib and dexamethasone or venezola, carfilzomib, IMiD (lenalidomide or pomalidomide) and dexamethasone
.

95% of patients are refractory to at least one PI and one IMiD
.

Thirty-four% of patients used the Veneclax dose escalation strategy
.

All patients did not develop tumor lysis syndrome, including those who did not use the dose-climbing method
.

86% of patients used antibacterial prophylaxis, including antiviral, antipneumocystis, antibacterial and antifungal treatments
.

3 The median follow-up time of the entire cohort of patients with short- and long-term efficacy was 11.
3 months
.

At the last follow-up, 32% of patients were still receiving Venecla
.

The overall response rate (ORR) of 52 patients with evaluable efficacy was 44%, of which the complete response (CR) rate was 21%, and the CR rate of patients with t(11;14) was higher than that of patients without t(11;14) The patients were 48% and 30%, but the difference was not statistically significant (P=0.
34)), see Figure 1 for details
.

Strong expression of BCL-2 was associated with higher ORR (P=0.
008)
.

The median to optimal response time for the entire cohort was 2 months, and the median duration of response was 13.
6 months
.

The median progression-free survival (PFS) of the entire cohort was 5.
8 months, and the median overall survival (OS) was 28.
4 months
.

Among them, patients with t(11;14) had better median PFS (9.
7 months vs 4.
2 months, P=0.
019) (Figure 2A) and median OS (not reached vs 10.
9 months, P=0.
015) (Figure 2A) 2B) Relevant
.

Among standard-risk patients, the median PFS of patients with or without t(11;14) was 14.
1 months and 7.
1 months (P=0.
56) (Figure 2C).
The median OS of both groups was not reached (P=0.
18) (Figure 2D)
.

Figure 1: Patient hematology remission Figure 2: Analysis of the PFS and OS of the entire cohort (A/B) and standard risk cytogenetics (C/D) patients according to t(11;14) status.
Compared with patients in the risk group, high-risk cytogenetic abnormalities were associated with shortened PFS (P=0.
0001) and OS (P<0.
0001)
.

Subgroup analysis showed that among patients with t(11;14), the median PFS of patients with and without high-risk cytogenetic abnormalities were 3.
4 months and 14.
1 months (P=0.
0063, Figure 3A)
.

Among non-t(11;14) patients, the median PFS of patients with and without high-risk cytogenetic abnormalities were 2.
6 months and 7.
1 months (P=0.
09, Figure 3B)
.

In t(11;14) patients, the median OS of patients with and without high-risk cytogenetic abnormalities was 13 months and not reached (P<0.
0001, Figure 3C)
.

Among patients without t(11;14), the median OS of patients with and without high-risk cytogenetics was 10 months and not reached (P=0.
33, Figure 3D)
.

Figure 3: PFS in patients with t(11;14)(A) and non-t(11;14)(B) by cytogenetic risk status, t(11;14)(C) and non-t(11) 14) (D) OS status in patients according to cytogenetic risk status 4 Toxic and side effects At the last follow-up, 24 patients (43%) died, and all patients had disease progression at the time of death
.

Pneumonia was the cause of death in 5 patients, of which 2 patients were receiving venecla as part of their last treatment at the time of death
.

The conclusion of the study is that Venecla has shown encouraging activity in R/R MM patients who have previously received multi-line therapy, especially those with t(11;14)
.

References: M Hasib Sidiqi, Abdullah S Al Saleh, Shaji K Kumar, et al.
Venetoclax for the treatment of multiple myeloma: Outcomes outside of clinical trials.
Am J Hematol.
2021 Sep 1;96(9):1131-1136.
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