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.

Basic information

Original name

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

Authors

MINARIK, Jiri (203 Czech Republic, guarantor), Jakub RADOCHA (203 Czech Republic), Alexandra JUNGOVA (203 Czech Republic), Jan STRAUB (203 Czech Republic), Tomas JELINEK (203 Czech Republic), Tomas PIKA (203 Czech Republic), Luděk POUR (203 Czech Republic, belonging to the institution), Petr PAVLICEK (203 Czech Republic), Lubica HARVANOVA (203 Czech Republic), Lenka POSPISILOVA (203 Czech Republic), Petra KRHOVSKA (203 Czech Republic), Denisa NOVAKOVA (203 Czech Republic), Pavel JINDRA (203 Czech Republic), Ivan SPICKA (203 Czech Republic), Hana PLONKOVA (203 Czech Republic), Martin ŠTORK (203 Czech Republic, belonging to the institution), Jaroslav BACOVSKY (203 Czech Republic), Vladimir MAISNAR (203 Czech Republic) and Roman HAJEK (203 Czech Republic)

Edition

Cancers, Basel, MDPI, 2022, 2072-6694

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.200

RIV identification code

RIV/00216224:14110/22:00128265

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000872608900001

Keywords in English

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

Abstract

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 and 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, vol. 14, No 20, p. 1-13. ISSN 2072-6694. Available from: 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 and 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, vol.~14, No~20, p.~1-13. ISSN~2072-6694. Available from: https://dx.doi.org/10.3390/cancers14205165.

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