Carfilzomib, Lenalidomide and Dexamethasone (KRd) Vs Bortezomib, Lenalidomide, and Dexamethasone (VRd) As Induction Therapy in Newly Diagnosed High-Risk Multiple Myeloma

Tan, Carlyn; Nemirovsky, David; Derkach, Andriy; Hultcrantz, Malin; Hassoun, Hani; Mailankody, Sham; Shah, Urvi; Patel, Dhwani; Maclachlan, Kylee; Lahoud, Oscar; Shah, Gunjan L.; Scordo, Michael; Chung, David J.; Landau, Heather; Giralt, Sergío; Lesokhin, Alexander M.; Korde, Neha; Usmani, Saad Z.

doi:10.1182/blood-2022-169161

Cited by 5 publications

(6 citation statements)

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“…Ultimately, VTE incidence was reported by five studies ( n = 2304) and ATE incidence was reported by four studies ( n = 2179). Although two retrospective cohorts involved overlapping populations from the same institution, Piedra et al exclusively reported VTE rates and Tan et al exclusively reported ATE rates, which allowed these studies to be analyzed separately for each outcome measure 12,15 …”

Section: Resultsmentioning

confidence: 99%

“…The distinctive thrombogenicity of two induction regimens commonly used for NDMM — carfilzomib/Rd (KRd) and bortezomib/Rd (VRd) — has been a matter of debate, with the current literature revealing divergent findings. For instance, Piedra et al demonstrated an increased VTE incidence among KRd‐treated patients in comparison with VRd‐treated patients, whereas Gaballa et al found no significant difference in thrombosis rates between these triplets 11–16 . In view of the foregoing, we decided to perform a systematic review and meta‐analysis aimed at comparing the thromboembolic risk associated with KRD versus VRD as frontline therapy for NDMM.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, Piedra et al demonstrated an increased VTE incidence among KRd-treated patients in comparison with VRd-treated patients, whereas Gaballa et al found no significant difference in thrombosis rates between these triplets. [11][12][13][14][15][16] In view of the foregoing, we decided to perform a systematic review and meta-analysis aimed at comparing the thromboembolic risk associated with KRD versus VRD as frontline therapy for NDMM.…”

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confidence: 99%

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Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta‐analysis

Costa,

Saravia

et al. 2024

American J Hematol

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Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta‐analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32–0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24–4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient‐level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta‐analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta‐analysis

Costa,

Saravia

et al. 2024

American J Hematol

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“…After a median follow-up of 34.4 months, 3-year PFS was 53.5% and 64% for KRD and VRD group, respectively ( p = 0.25), with no difference reported for OS, not reached for either group ( p = 0.30). The second study evaluated 154 NDMM HR patients treated at Memorial Sloan Kettering Cancer Center [ 109 ], who, after induction with VRD or KRD, received early ASCT (77 patients) or no early ASCT (77 patients). In the subgroup of patients undergoing early ASCT, 5-year PFS from ASCT was 24% for VRD and 60% for KRD (HR = 0.49, p = 0.04) with 5-year OS of 53% and 87%, respectively (HR = 0.39, p = 0.09).…”

Section: High Risk Multiple Myeloma and Risk-adapted Therapiesmentioning

confidence: 99%

Current Main Topics in Multiple Myeloma

Morè¹,

Corvatta²,

Manieri³

et al. 2023

Cancers

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Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of PFS and OS.; however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). Patients who become refractory to conventional therapies have noticeably poor outcomes, making their treatment a difficult challenge in need of novel strategies. In this review, we will focus on the main points regarding risk stratification, treatment and monitoring of MM, highlighting the most recent evidence that could modify the management of this still incurable disease.

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“…Table S1 summarizes study baseline characteristics. [3][4][5] In the pooled analyses for the overall population, KRd-treated and VRd-treated subjects demonstrated no significant differences in PFS (HR = 0.84; 95% CI = 0.61-1.15; p = .27; I 2 = 55%; Figure 1A), OS (HR = 0.77; 95% CI = 0.42-1.44; p = .41; I 2 = 61%; Figure 1B), or ORR (OR, 0.32; 95% CI = 0.07-1.43; p = .14; I 2 = 75%; Figure 1C). In comparison to the carfilzomib arm, the bortezomib arm showed 36% lower odds of achieving CR/sCR (OR, 0.64; 95% CI = 0.44-0.92; p = .02; I 2 = 43%; Figure 1D) and 38% lower odds of achieving MRD negativity (OR, 0.62; 95% CI = 0.45-0.86; p = .003; 1E).…”

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Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly‐diagnosed multiple myeloma: A systematic review and meta‐analysis

Costa,

Pak

et al. 2024

American J Hematol

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The treatment paradigm of newly-diagnosed multiple myeloma (NDMM) has undergone a profound change over the past few decades, with induction regimens evolving beyond the traditional steroid/alkylator backbones to highly effective combinations incorporating immunomodulatory drugs, proteasome inhibitors, and/or monoclonal antibodies. 1 As a result, recent large-scale studies of patients treated in resource-rich settings have reported an impressive overall survival (OS) of around 126 months. 2 However, given the numerous options of primary therapy currently endorsed by consensus guidelines, there is ongoing discussion about the relative safety and efficacy of the combinations available. While ENDURANCE-a multicenter, open-label, phase 3, randomized controlled trial (RCT)-found no significant difference in progression-free survival (PFS) between previously-untreated patients without intention for immediate autologous stem cell transplantation receiving carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd), subsequent real-world results from NDMM cohorts have varied. 3-5 Moreover, the practical use of carfilzomib-based induction in frontline settings continues to rise. Considering this dilemma, we conducted a systematic review and meta-analysis (SRMA) comparing efficacy outcomes between patients treated with KRd versus VRd as first-line induction for NDMM. This study adhered to the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Our

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Carfilzomib, Lenalidomide and Dexamethasone (KRd) Vs Bortezomib, Lenalidomide, and Dexamethasone (VRd) As Induction Therapy in Newly Diagnosed High-Risk Multiple Myeloma

Cited by 5 publications

References 0 publications

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta‐analysis

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta‐analysis

Current Main Topics in Multiple Myeloma

Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly‐diagnosed multiple myeloma: A systematic review and meta‐analysis

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