Dataset Information

Efficacy and safety of Venetoclax-based regimens in relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials.

ABSTRACT:

Background

Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard therapies.

Objective

This study aimed to assess the efficacy and safety of VEN-based treatments in RR MM patients.

Materials and methods

Comprehensive studies were searched in PubMed, Embase, Web of Science and Cochrane library. Efficacy was assessed by overall response rate (ORR), strict complete response rate (sCR), complete response rate (CR), very good partial response rate (VGPR) and partial response rate (PR).

Results

Seven studies containing 482 subjests were included. The pooled ORR, ≥ CR (sCR + CR), VGPR and PR were 68% (51%-85%), 24% (13%-35%), 25% (17%-34%) and 17% (11%-24%) respectively. Multi-drug treatments were superior to VEN ± dexamethasone (Dex) treatments in ORR (82% vs 42%, p = .003) and ≥ CR (36% vs 7%, p < 0.00001). Subgroup analysis indicated patients achieve higher ORR who harboring t(11;14) translocation or containing high BCL-2 expression.

Conclusions

VEN-containing regimens could be suggested as effective and safe treatments to RR MM patients with t(11;14) or high BCL-2 levels.

SUBMITTER: He W

PROVIDER: S-EPMC10795640 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of Venetoclax-based regimens in relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials.

He Wei W He Fang F Hu Huixian H

Annals of medicine 20231201 1

<h4>Background</h4>Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard therapies.<h4>Objective</h4>This study aimed to assess the efficacy and safety of VEN-based treatments in RR MM patients.<h4>Materials and methods</h4>Comprehensive studies were searched in PubMed, Embase, Web of Science and Cochrane library. Efficacy was assessed by overall response rate (ORR), strict complete res ...[more]

PMID: 36911885

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Project description:Background: Patients with relapsed/refractory multiple myeloma (RRMM) usually have dismal prognostic outcomes. Venetoclax, a selective inhibitor of antiapoptotic protein B-cell lymphoma-2 (BCL-2), demonstrates antimyeloma activity in plasma cells with t(11;14) or high BCL-2 expression. Objectives: This meta-analysis aimed to investigate the efficacy and safety of venetoclax-based therapy in RRMM. Design: This is a meta-analysis study. Data Sources and Methods: PubMed, Embase, and Cochrane were searched for studies published up to 20 December 2021. Overall response rate (ORR), rate of very good partial response or better (≧VGPR), and complete response (CR) rate were pooled with the random-effects model. Safety was evaluated by the incidences of grade ≧3 adverse events. Subgroup analysis and meta-regression were performed to identify the causes of heterogeneities. All the analyses were conducted by STATA 15.0 software. Results: A total of 14 studies with 713 patients were included for analysis. The pooled ORR, rate of ≧VGPR, and CR for all patients were 59% [95% confidence interval (CI) = 45–71%], 38% (95% CI = 26–51%), and 17% (95% CI = 10–26%), respectively. The median progression-free survival (PFS) ranged from 2.0 months to not reached (NR), and the median overall survival (OS) ranged from 12.0 months to NR. Meta-regression showed that patients treated with more drugs combined or less heavily pretreated had higher response rates. Patients with t(11;14) had superior ORR [relative risk (RR) = 1.47, 95% CI = 1.05–2.07], ≧VGPR (RR = 1.71, 95% CI = 1.12–2.60), CR (RR = 1.86, 95% CI = 1.34–2.57), PFS [hazard ratio (HR) = 0.47, 95% CI = 0.30–0.65], and OS (HR = 0.30, 95% CI = 0.08–0.52) compared with patients without t(11;14). Most grade ≧3 adverse events were hematologic, gastrointestinal, and infectious related and were manageable. Conclusion: Venetoclax-based therapy is an effective and safe option for RRMM patients, especially those with t(11;14).

Project description:ObjectiveBispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.MethodsPubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.ResultsFourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% vs. 54%, P < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% vs. 18%, P < 0.01; grade ≥ 3: 43% vs. 15%, P < 0.01) and lymphopenia (any grade: 37% vs. 8%, P < 0.01; grade ≥ 3: 31% vs. 8%, P = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% vs. 66%, P = 0.84; grade ≥ 3: 1% vs. 1%, P = 0.36) and infections (any grade: 47% vs. 49%, P = 0.86; grade ≥ 3: 24% vs. 20%, P = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% vs. 2%, P < 0.01) and lower risks of fatigue (any grade: 14% vs. 30%, P < 0.01) and pyrexia (any grade: 14% vs. 29%, P < 0.01).ConclusionThis analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.

Project description:Background: In recent years, chimeric antigen receptor-modified T (CAR-T) cell therapy for B-cell leukemia and lymphoma has shown high clinical efficacy. Similar CAR-T clinical trials have also been carried out in patients with refractory/relapsed multiple myeloma (RRMM). However, no systematic review has evaluated the efficacy and safety of CAR-T cell therapy in RRMM. The purpose of this study was to fill this literature gap. Methods: Eligible studies were searched in PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, and WanFang from data inception to December 2019. For efficacy assessment, the overall response rate (ORR), minimal residual disease (MRD) negativity rate, strict complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) were calculated. The incidence of any grade cytokine release syndrome (CRS) and grade ≥3 adverse events (AEs) were calculated for safety analysis. The effect estimates were then pooled using an inverse variance method. Results: Overall, 27 studies involving 497 patients were included in this meta-analysis. The pooled ORR and MRD negativity rate were 89% (95% Cl: 83-94%) and 81% (95% Cl: 67-91%), respectively. The pooled sCR, CR, VGPR, and PR were 14% (95% Cl: 5-27%), 13% (95% Cl: 4-26%), 23% (95% Cl: 14-33%), and 15% (95% Cl: 10-21%), respectively. Subgroup analyses of ORR by age, proportion of previous autologous stem cell transplantation (ASCT), and target selection of CAR-T cells revealed that age ≤ 55 years (≤55 years vs. > 55 years, p = 0.0081), prior ASCT ≤70% (≤70% vs. > 70%, p = 0.035), and bispecific CAR-T cells (dual B-cell maturation antigen (BCMA)/BCMA + CD19 vs specific BCMA, p = 0.0329) associated with higher ORR in patients. Subgroup analyses of remission depth by target selection suggested that more patients achieved a better response than VGPR with dual BCMA/BCMA + CD19 CAR-T cells compared to specific BCMA targeting (p = 0.0061). In terms of safety, the pooled incidence of any grade and grade ≥ 3 CRS was 76% (95% CL: 63-87%) and 11% (95% CL: 6-17%). The most common grade ≥ 3 AEs were hematologic toxic effects. Conclusion: In heavily treated patients, CAR-T therapy associates with promising responses and tolerable AEs, as well as CRS in RRMM. However, additional information regarding the durability of CAR-T cell therapy, as well as further randomized controlled trials, is needed.

Dataset Information

Efficacy and safety of Venetoclax-based regimens in relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials.

Background

Objective

Materials and methods

Results

Conclusions

Publications

Efficacy and safety of Venetoclax-based regimens in relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials.

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