Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F22%3A10445243" target="_blank" >RIV/00064165:_____/22:10445243 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00098892:_____/22:10157307 RIV/00216208:11110/22:10445243 RIV/61989592:15110/22:73614764

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=meP_dWgSZt" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=meP_dWgSZt</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S1470-2045(22)00019-5" target="_blank" >10.1016/S1470-2045(22)00019-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study

Popis výsledku v původním jazyce

Background: The primary analysis of the ICARIA-MM study showed significant improvement in progression-free survival with addition of isatuximab to pomalidomide-dexamethasone in relapsed and refractory multiple myeloma. Here, we report a prespecified updated overall survival analysis at 24 months after the primary analysis. Methods: In this randomised, multicentre, open-label, phase 3 study adult patients (aged &gt;=18 years) with relapsed and refractory multiple myeloma who had received at least two previous lines of therapy, including lenalidomide and a proteasome inhibitor, and had an Eastern Cooperative Oncology Group performance status of 0-2 were recruited from 102 hospitals in 24 countries across Europe, North America, and the Asia-Pacific regions. Patients were excluded if they had anti-CD38 refractory disease or previously received pomalidomide. Patients were randomly assigned (1:1), using an interactive response technology with permuted blocked randomisation (block size of four) and stratified by number of previous treatment lines (2-3 vs &gt;3) and aged (&lt;75 vs &gt;=75 years), to isatuximab-pomalidomide-dexamethasone (isatuximab group) or pomalidomide-dexamethasone (control group). In the isatuximab group, intravenous isatuximab 10 mg/kg was administered on days 1, 8, 15, and 22 of the first 4-week cycle, and then on days 1 and 15 of subsequent cycles. Both groups received oral pomalidomide 4 mg on days 1-21 of each cycle, and weekly oral or intravenous dexamethasone 40 mg (20 mg if aged &gt;=75 years) on days 1, 8, 15, and 22 of each cycle. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Here&apos; we report a prespecified second interim analysis of overall survival (time from randomisation to any-cause death), a key secondary endpoint, in the intention-to-treat population (ie, all patients who provided informed consent and allocated a randomisation number) at 24 months after the primary analysis. Safety was assessed in all patients who received at least one dose or part dose of study treatment. The prespecified stopping boundary for the overall survival analysis was when the derived p value was equal to or less than 0.0181. This study is registered with ClinicalTrials.gov, NCT02990338, and is active, but not recruiting. Findings: Between Jan 10, 2017, and Feb 2, 2018, 387 patients were screened and 307 randomly assigned to either the isatuximab (n=154) or control group (n=153). Median follow-up at data cutoff (Oct 1, 2020) was 35.3 months (IQR 33.5-37.4). Median overall survival was 24.6 months (95% CI 20.3-31.3) in the isatuximab group and 17.7 months (14.4-26.2) in the control group (hazard ratio 0.76 [95% CI 0.57-1.01]; one-sided log-rank p=0.028, not crossing prespecified stopping boundary). The most common grade 3 or worse treatment-emergent adverse events in the isatuximab group versus the control group were neutropenia (76 [50%] of 152 patients vs 52 [35%] of 149 patients), pneumonia (35 [23%] vs 31 [21%]), and thrombocytopenia (20 [13%] vs 18 [12%]). Serious treatment-emergent adverse events were observed in 111 (73%) patients in the isatuximab group and 90 (60%) patients in the control group. Two (1%) treatment-related deaths occurred in the isatuximab group (one due to sepsis and one due to cerebellar infarction) and two (1%) occurred in the control group (one due to pneumonia and one due to urinary tract infection). Interpretation: Addition of isatuximab plus pomalidomide-dexamethasone resulted in a 6.9-month difference in median overall survival compared with pomalidomide-dexamethasone and is a new standard of care for lenalidomide-refractory and proteasome inhibitor-refractory or relapsed multiple myeloma. Final overall survival analysis follow-up is ongoing.

Název v anglickém jazyce

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study

Popis výsledku anglicky

Background: The primary analysis of the ICARIA-MM study showed significant improvement in progression-free survival with addition of isatuximab to pomalidomide-dexamethasone in relapsed and refractory multiple myeloma. Here, we report a prespecified updated overall survival analysis at 24 months after the primary analysis. Methods: In this randomised, multicentre, open-label, phase 3 study adult patients (aged &gt;=18 years) with relapsed and refractory multiple myeloma who had received at least two previous lines of therapy, including lenalidomide and a proteasome inhibitor, and had an Eastern Cooperative Oncology Group performance status of 0-2 were recruited from 102 hospitals in 24 countries across Europe, North America, and the Asia-Pacific regions. Patients were excluded if they had anti-CD38 refractory disease or previously received pomalidomide. Patients were randomly assigned (1:1), using an interactive response technology with permuted blocked randomisation (block size of four) and stratified by number of previous treatment lines (2-3 vs &gt;3) and aged (&lt;75 vs &gt;=75 years), to isatuximab-pomalidomide-dexamethasone (isatuximab group) or pomalidomide-dexamethasone (control group). In the isatuximab group, intravenous isatuximab 10 mg/kg was administered on days 1, 8, 15, and 22 of the first 4-week cycle, and then on days 1 and 15 of subsequent cycles. Both groups received oral pomalidomide 4 mg on days 1-21 of each cycle, and weekly oral or intravenous dexamethasone 40 mg (20 mg if aged &gt;=75 years) on days 1, 8, 15, and 22 of each cycle. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Here&apos; we report a prespecified second interim analysis of overall survival (time from randomisation to any-cause death), a key secondary endpoint, in the intention-to-treat population (ie, all patients who provided informed consent and allocated a randomisation number) at 24 months after the primary analysis. Safety was assessed in all patients who received at least one dose or part dose of study treatment. The prespecified stopping boundary for the overall survival analysis was when the derived p value was equal to or less than 0.0181. This study is registered with ClinicalTrials.gov, NCT02990338, and is active, but not recruiting. Findings: Between Jan 10, 2017, and Feb 2, 2018, 387 patients were screened and 307 randomly assigned to either the isatuximab (n=154) or control group (n=153). Median follow-up at data cutoff (Oct 1, 2020) was 35.3 months (IQR 33.5-37.4). Median overall survival was 24.6 months (95% CI 20.3-31.3) in the isatuximab group and 17.7 months (14.4-26.2) in the control group (hazard ratio 0.76 [95% CI 0.57-1.01]; one-sided log-rank p=0.028, not crossing prespecified stopping boundary). The most common grade 3 or worse treatment-emergent adverse events in the isatuximab group versus the control group were neutropenia (76 [50%] of 152 patients vs 52 [35%] of 149 patients), pneumonia (35 [23%] vs 31 [21%]), and thrombocytopenia (20 [13%] vs 18 [12%]). Serious treatment-emergent adverse events were observed in 111 (73%) patients in the isatuximab group and 90 (60%) patients in the control group. Two (1%) treatment-related deaths occurred in the isatuximab group (one due to sepsis and one due to cerebellar infarction) and two (1%) occurred in the control group (one due to pneumonia and one due to urinary tract infection). Interpretation: Addition of isatuximab plus pomalidomide-dexamethasone resulted in a 6.9-month difference in median overall survival compared with pomalidomide-dexamethasone and is a new standard of care for lenalidomide-refractory and proteasome inhibitor-refractory or relapsed multiple myeloma. Final overall survival analysis follow-up is ongoing.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

The Lancet: Oncology

ISSN

1470-2045

e-ISSN

1474-5488

Svazek periodika

23

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

416-427

Kód UT WoS článku

000820112600045

EID výsledku v databázi Scopus

2-s2.0-85125406486