Ixazomib, Lenalidomide and Dexamethasone in Relapsed and
Refractory Multiple Myeloma in Routine Clinical Practice:
Extended Follow-Up Analysis and the Results of Subsequent
Therapy

J 2022

Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy

MINARIK, Jiri, Jakub RADOCHA, Alexandra JUNGOVA, Jan STRAUB, Tomas JELINEK et. al.

Základní údaje

Originální název

Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy

Autoři

MINARIK, Jiri (203 Česká republika, garant), Jakub RADOCHA (203 Česká republika), Alexandra JUNGOVA (203 Česká republika), Jan STRAUB (203 Česká republika), Tomas JELINEK (203 Česká republika), Tomas PIKA (203 Česká republika), Luděk POUR (203 Česká republika, domácí), Petr PAVLICEK (203 Česká republika), Lubica HARVANOVA (203 Česká republika), Lenka POSPISILOVA (203 Česká republika), Petra KRHOVSKA (203 Česká republika), Denisa NOVAKOVA (203 Česká republika), Pavel JINDRA (203 Česká republika), Ivan SPICKA (203 Česká republika), Hana PLONKOVA (203 Česká republika), Martin ŠTORK (203 Česká republika, domácí), Jaroslav BACOVSKY (203 Česká republika), Vladimir MAISNAR (203 Česká republika) a Roman HAJEK (203 Česká republika)

Vydání

Cancers, Basel, MDPI, 2022, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.200

Kód RIV

RIV/00216224:14110/22:00128265

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3390/cancers14205165

UT WoS

000872608900001

Klíčová slova anglicky

multiple myeloma; relapsed and refractory; real-world analysis; immunomodulatory drugs; proteasome inhibitors

Štítky

14110212, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 1. 2023 10:56, Mgr. Tereza Miškechová

Anotace

V originále

We report the final outomes of the addition of ixazomib to the combination of lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma in the routine clinical practice. With prolonged follow-up, the overall response rate was similar in both cohorts, but the addition of ixazomib induced more deeper responses. Median progression free survival was significantly better in patients receiving ixazomib and translated into better overal survival. Inferior results were seen in patients who were pretreated with lenalidomide in previous regimens. We conclude that the treatment using IRD regimen in routine practice is easy, well tolerated, and with very good therapeutic outcomes, comparable to the outcomes of the clinical trial. Background: We confirmed the benefit of addition of ixazomib to lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) in unselected real-world population. We report the final analysis for overall survival (OS), second progression free survival (PFS-2), and the subanalysis of the outcomes in lenalidomide (LEN) pretreated and LEN refractory patients. Methods: We assessed 344 patients with RRMM, treated with IRD (N = 127) or RD (N = 217). The data were acquired from the Czech Registry of Monoclonal Gammopathies (RMG). With prolonged follow-up (median 28.5 months), we determined the new primary endpoints OS, PFS and PFS-2. Secondary endpoints included the next therapeutic approach and the survival measures in LEN pretreated and LEN refractory patients. Results: The final overall response rate (ORR) was 73.0% in the IRD cohort and 66.8% in the RD cohort. The difference in patients reaching >= VGPR remained significant (38.1% vs. 26.3%, p = 0.028). Median PFS maintained significant improvement in the IRD cohort (17.5 vs. 12.5 months, p = 0.013) with better outcomes in patients with 1-3 prior relapses (22.3 vs. 12.7 months p = 0.003). In the whole cohort, median OS was for IRD vs. RD patients 40.9 vs. 27.1 months (p = 0.001), with further improvement within relapse 1-3 (51.7 vs. 27.8 months, p < 0.001). The median PFS of LEN pretreated (N = 22) vs. LEN naive (N = 105) patients treated by IRD was 8.7 vs. 23.1 months (p = 0.001), and median OS was 13.2 vs. 51.7 months (p = 0.030). Most patients in both arms progressed and received further myeloma-specific therapy (63.0% in the IRD group and 53.9% in the RD group). Majority of patients received pomalidomide-based therapy or bortezomib based therapy. Significantly more patients with previous IRD vs. RD received subsequent monoclonal antibodies (daratumumab-16.3% vs. 4.3%, p = 0.0054; isatuximab 5.0% vs. 0.0%, p = 0.026) and carfilzomib (12.5 vs. 1.7%, p = 0.004). The median PFS-2 (progression free survival from the start of IRD/RD therapy until the second disease progression or death) was significantly longer in the IRD cohort (29.8 vs. 21.6 months, p = 0.016). There were no additional safety concerns in the extended follow-up. Conclusions: The IRD regimen is well tolerated, easy to administer, and with very good therapeutic outcomes. The survival measures in unsorted real-world population are comparable to the outcomes of the clinical trial. As expected, patients with LEN reatment have poorer outcomes than those who are LEN-naive. The PFS benefit of IRD vs. RD translated into significantly better PFS-2 and OS, but the outcomes must be accounted for imbalances in pretreatment group characteristics (especially younger age and stem cell transplant pretreatment), and in subsequent therapies.

Citovat

MINARIK, Jiri, Jakub RADOCHA, Alexandra JUNGOVA, Jan STRAUB, Tomas JELINEK, Tomas PIKA, Luděk POUR, Petr PAVLICEK, Lubica HARVANOVA, Lenka POSPISILOVA, Petra KRHOVSKA, Denisa NOVAKOVA, Pavel JINDRA, Ivan SPICKA, Hana PLONKOVA, Martin ŠTORK, Jaroslav BACOVSKY, Vladimir MAISNAR a Roman HAJEK. Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy. Cancers. Basel: MDPI, 2022, roč. 14, č. 20, s. 1-13. ISSN 2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers14205165.

@article{2249587,
   author = {Minarik, Jiri and Radocha, Jakub and Jungova, Alexandra and Straub, Jan and Jelinek, Tomas and Pika, Tomas and Pour, Luděk and Pavlicek, Petr and Harvanova, Lubica and Pospisilova, Lenka and Krhovska, Petra and Novakova, Denisa and Jindra, Pavel and Spicka, Ivan and Plonkova, Hana and Štork, Martin and Bacovsky, Jaroslav and Maisnar, Vladimir and Hajek, Roman},
   article_location = {Basel},
   article_number = {20},
   doi = {http://dx.doi.org/10.3390/cancers14205165},
   keywords = {multiple myeloma; relapsed and refractory; real-world analysis; immunomodulatory drugs; proteasome inhibitors},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy},
   url = {https://www.mdpi.com/2072-6694/14/20/5165},
   volume = {14},
   year = {2022}
}

TY  - JOUR
ID  - 2249587
AU  - Minarik, Jiri - Radocha, Jakub - Jungova, Alexandra - Straub, Jan - Jelinek, Tomas - Pika, Tomas - Pour, Luděk - Pavlicek, Petr - Harvanova, Lubica - Pospisilova, Lenka - Krhovska, Petra - Novakova, Denisa - Jindra, Pavel - Spicka, Ivan - Plonkova, Hana - Štork, Martin - Bacovsky, Jaroslav - Maisnar, Vladimir - Hajek, Roman
PY  - 2022
TI  - Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy
JF  - Cancers
VL  - 14
IS  - 20
SP  - 1-13
EP  - 1-13
PB  - MDPI
SN  - 20726694
KW  - multiple myeloma
KW  - relapsed and refractory
KW  - real-world analysis
KW  - immunomodulatory drugs
KW  - proteasome inhibitors
UR  - https://www.mdpi.com/2072-6694/14/20/5165
N2  - We report the final outomes of the addition of ixazomib to the combination of lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma in the routine clinical practice. With prolonged follow-up, the overall response rate was similar in both cohorts, but the addition of ixazomib induced more deeper responses. Median progression free survival was significantly better in patients receiving ixazomib and translated into better overal survival. Inferior results were seen in patients who were pretreated with lenalidomide in previous regimens. We conclude that the treatment using IRD regimen in routine practice is easy, well tolerated, and with very good therapeutic outcomes, comparable to the outcomes of the clinical trial. Background: We confirmed the benefit of addition of ixazomib to lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) in unselected real-world population. We report the final analysis for overall survival (OS), second progression free survival (PFS-2), and the subanalysis of the outcomes in lenalidomide (LEN) pretreated and LEN refractory patients. Methods: We assessed 344 patients with RRMM, treated with IRD (N = 127) or RD (N = 217). The data were acquired from the Czech Registry of Monoclonal Gammopathies (RMG). With prolonged follow-up (median 28.5 months), we determined the new primary endpoints OS, PFS and PFS-2. Secondary endpoints included the next therapeutic approach and the survival measures in LEN pretreated and LEN refractory patients. Results: The final overall response rate (ORR) was 73.0% in the IRD cohort and 66.8% in the RD cohort. The difference in patients reaching >= VGPR remained significant (38.1% vs. 26.3%, p = 0.028). Median PFS maintained significant improvement in the IRD cohort (17.5 vs. 12.5 months, p = 0.013) with better outcomes in patients with 1-3 prior relapses (22.3 vs. 12.7 months p = 0.003). In the whole cohort, median OS was for IRD vs. RD patients 40.9 vs. 27.1 months (p = 0.001), with further improvement within relapse 1-3 (51.7 vs. 27.8 months, p < 0.001). The median PFS of LEN pretreated (N = 22) vs. LEN naive (N = 105) patients treated by IRD was 8.7 vs. 23.1 months (p = 0.001), and median OS was 13.2 vs. 51.7 months (p = 0.030). Most patients in both arms progressed and received further myeloma-specific therapy (63.0% in the IRD group and 53.9% in the RD group). Majority of patients received pomalidomide-based therapy or bortezomib based therapy. Significantly more patients with previous IRD vs. RD received subsequent monoclonal antibodies (daratumumab-16.3% vs. 4.3%, p = 0.0054; isatuximab 5.0% vs. 0.0%, p = 0.026) and carfilzomib (12.5 vs. 1.7%, p = 0.004). The median PFS-2 (progression free survival from the start of IRD/RD therapy until the second disease progression or death) was significantly longer in the IRD cohort (29.8 vs. 21.6 months, p = 0.016). There were no additional safety concerns in the extended follow-up. Conclusions: The IRD regimen is well tolerated, easy to administer, and with very good therapeutic outcomes. The survival measures in unsorted real-world population are comparable to the outcomes of the clinical trial. As expected, patients with LEN reatment have poorer outcomes than those who are LEN-naive. The PFS benefit of IRD vs. RD translated into significantly better PFS-2 and OS, but the outcomes must be accounted for imbalances in pretreatment group characteristics (especially younger age and stem cell transplant pretreatment), and in subsequent therapies.
ER  -

MINARIK, Jiri, Jakub RADOCHA, Alexandra JUNGOVA, Jan STRAUB, Tomas JELINEK, Tomas PIKA, Luděk POUR, Petr PAVLICEK, Lubica HARVANOVA, Lenka POSPISILOVA, Petra KRHOVSKA, Denisa NOVAKOVA, Pavel JINDRA, Ivan SPICKA, Hana PLONKOVA, Martin ŠTORK, Jaroslav BACOVSKY, Vladimir MAISNAR a Roman HAJEK. Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy. \textit{Cancers}. Basel: MDPI, 2022, roč.~14, č.~20, s.~1-13. ISSN~2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers14205165.

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