Carfilzomib in addition to lenalidomide and dexamethasone in Asian patients with RRMM outside of a clinical trial

Lee, Ji Hyun; Park, Yong; Kang, Ka-Won; Lee, Je‐Jung; Lee, Ho Sup; Eom, Hyeon-Seok; Rok, Young; Kim, Jin Seok; Yoon, Sung‐Soo; Shin, Dong‐Yeop; Koh, Youngil; Kım, Kihyun; Lee, Won Sik; Jo, Jae‐Cheol; Lee, Yoo Jin; Lee, Ji Yun; Kim, Dae Sik; Shim, Hyeok; Chang, Myung Hee; Kim, Sung-Hyun; Min, Chang‐Ki

doi:10.1007/s00277-021-04407-0

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…For example, the ASPIRE trial showed an ORR of 87% [11] with PFS of 26.3 months and OS 48.3 months [12] with a median of two prior lines of therapy compared, whereas the two prior line KRd cohort in our study had an ORR of 64%, median PFS of 5.6 months, and median OS of 10.9 months. Our findings are similar to those reported in other real‐world studies, including an analysis of 208 patients with RRMM treated with KRd after median two prior lines showing a median time to next treatment of 8.6 months, as well as other studies showing similar PFS ranges [29–32]. The PFS in our study was longest in the KCd cohort in lines 2 and 3.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Carfilzomib usage patterns and outcomes in patients with relapsed multiple myeloma: A multi‐institutional report from the Canadian Myeloma Research Group (CMRG) Database

McCurdy

Louzada

Venner

et al. 2022

eJHaem

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Carfilzomib is an active and commonly used treatment in patients with multiple myeloma (MM). Using the Canadian Myeloma Research Group Database, we performed a retrospective observational study of patients treated with carfilzomib for relapse of MM in a real‐world setting in Canada between years 2007 and 2020. A total of 445 patients were included in this study: the doublet (Kd/p, n = 218) and triplets (KCd, n = 88; KRd, n = 99; KPd/p, n = 40). One hundred and twenty‐two (27%) received carfilzomib‐based treatment in line 2, 133 (30%) in line 3, 90 (20%) in line 4, and 100 (23%) in line 5 or higher. Carfilzomib was dosed weekly in 40% of patients and twice weekly in 60%. The overall response rate of the entire cohort was 57.7%, with 33.6% of patients achieving very good partial response or better. Median progression‐free survival for the overall cohort was 6.3 months with overall survival 19.7 months. This study provides a benchmark for carfilzomib‐based regimens in the real world, demonstrating that these regimens are effective in treating patients with relapsed MM.

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Section: Discussionsupporting

confidence: 91%

“…analysis of 208 patients with RRMM treated with KRd after median two prior lines showing a median time to next treatment of 8.6 months, as well as other studies showing similar PFS ranges[29][30][31][32]. The PFS in our study was longest in the KCd cohort in lines 2 and 3.…”

supporting

confidence: 84%

Carfilzomib usage patterns and outcomes in patients with relapsed multiple myeloma: A multi‐institutional report from the Canadian Myeloma Research Group (CMRG) Database

McCurdy

Louzada

Venner

et al. 2022

eJHaem

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“…The trend of the risk of adverse events in this study and the ASPIRE trial was similar, but not significant. Note that most of the other research on the real-world safety of carfilzomib analyzed about 100 study subjects, which is similar to the number of our study subjects ( n = 197, Italy [ 17 ]; n = 156, US [ 5 ]; n = 55, Korea [ 20 ]; n = 40, Korea [ 8 ]). Our study used a similar or larger number of study subjects to present the integrated safety results for carfilzomib.…”

Section: Discussionsupporting

confidence: 69%

“…Second, most of the studies of carfilzomib were performed on white populations [ 5 , 9 , 10 , 16 , 17 ], and the safety of minority populations were not discussed. There are only a few real-world safety studies for non-white populations [ 8 , 18 , 19 , 20 ]; however, they focused on the efficacy or cardiovascular safety only. The side effects of chemotherapy can vary greatly owing to differences in clinical settings and ethnicity.…”

Section: Introductionmentioning

confidence: 99%

Carfilzomib’s Real-World Safety Outcomes in Korea: Target Trial Emulation Study Using Electronic Health Records

Jang

Lee

Kim

et al. 2022

IJERPH

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Carfilzomib is a promising anticancer drug for relapsed/refractory multiple myeloma (RRMM). However, real-world evidence has only investigated the cardiovascular safety of carfilzomib, and there is a high demand for thorough safety evaluations. We aimed to comprehensively evaluate the risk of adverse events associated with carfilzomib in Korean patients with RRMM. We followed up with 138 matched patients with RRMM (69 KRd (carfilzomib, lenalidomide, and dexamethasone) and 69 Rd (lenalidomide and dexamethasone) users). A total of 12 adverse events were evaluated. More than 75% of adverse events occurred during the early cycle (1–6 cycles), and the incidence rate showed a tendency to decrease in the later cycle (7–12 and 13–18 cycles). Severities of most adverse events were evaluated as grade 1-2. The KRd regimen were related with significantly increased risks of dyspnea (adjusted HR (aHR) 2.27, 95% confidence interval (CI) 1.24–4.16), muscle spasm (aHR 5.12, 95% CI 1.05–24.9) and thrombocytopenia (aHR 1.84, 95% CI 1.10–3.06). Although the severities were low, carfilzomib has many side effects in treating RRMM; hence, findings on the patterns of its adverse events could lead to both effective and safe use of KRd therapy in real-world settings.

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“…Since then, retrospective real-life investigations have reported the use of the KRd combination in patients with relapsed/refractory multiple myeloma (RRMM) describing its safety and efficacy profiles in heavily pre-treated and very heterogeneous patient populations (9)(10)(11)(12)(13). The latest of these, a recent Italian study, reported a joint analysis of 600 RRMM patients treated with KRd, confirming the efficacy of this combination in the real-life context and identifying previous lenalidomide exposure, high-risk cytogenetic alterations, International Staging System (ISS) advanced, and severe renal insufficiency as factors with a negative prognostic impact (14).…”

Section: Introductionmentioning

confidence: 99%

Carfilzomib, lenalidomide, and dexamethasone in relapsed refractory multiple myeloma: a prospective real-life experience of the Regional Tuscan Myeloma Network

et al. 2023

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IntroductionCarfilzomib, a potent, irreversible, selective proteasome inhibitor has demonstrated consistent results in relapsed/refractory multiple myeloma (RRMM) combined with lenalidomide and dexamethasone (KRd). No prospective studies are yet available that analyzed the efficacy of the KRd combination.MethodsHerein, we report a multicenter prospective observational study on 85 patients who were treated with KRd combination as the second or third line of treatment, according to standard practice.ResultsThe median age was 61 years; high-risk cytogenetic was found in 26% and renal impairment (estimated glomerular filtration rate (eGFR) <60 ml/min) in 17%. After a median follow-up of 40 months, patients received a median number of 16 cycles of KRd, with a median duration of treatment (DoT) of 18 months (range, 16.1–19.2 months). The overall response rate was 95%, with a high-quality response (≥very good partial remission [VGPR]) in 57% of the patients. The median progression-free survival (PFS) was 36 months (range, 29.1–43.2 months). Achievement of at least VGPR and a previous autologous stem cell transplantation (ASCT) were associated with longer PFS. The median overall survival (OS) was not reached (NR); the 5-year OS rate was 73%. Nineteen patients underwent KRd treatment as a bridge to autologous transplantation, obtaining a post-transplant minimal residual disease (MRD) negativity in 65% of cases. The most common adverse events were hematological, followed by infection and cardiovascular events, rarely G3 or higher, with a discontinuation rate for toxicities of 6%. Our data confirmed the feasibility and safety of the KRd regimen in real life.

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Carfilzomib in addition to lenalidomide and dexamethasone in Asian patients with RRMM outside of a clinical trial

Cited by 7 publications

References 22 publications

Carfilzomib usage patterns and outcomes in patients with relapsed multiple myeloma: A multi‐institutional report from the Canadian Myeloma Research Group (CMRG) Database

Carfilzomib usage patterns and outcomes in patients with relapsed multiple myeloma: A multi‐institutional report from the Canadian Myeloma Research Group (CMRG) Database

Carfilzomib’s Real-World Safety Outcomes in Korea: Target Trial Emulation Study Using Electronic Health Records

Carfilzomib, lenalidomide, and dexamethasone in relapsed refractory multiple myeloma: a prospective real-life experience of the Regional Tuscan Myeloma Network

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