Combination Experience of Ixazomib, Lenalidomide, Dexamethasone in Relapsed Refractory Multiple Myeloma: Real-Life Data
Öz
Ixazomib, the first oral proteasome inhibitor (PI), is approved for treating relapsed refractory multiple myeloma (RRMM) in combination with lenalidomide and dexamethasone. However, clinical trial results do not always match real-world results. This study aimed to evaluate the results of ixazomib-based combination therapy for the treatment of patients with RRMM in real life. A total of 45 patients with RRMM from the Bursa Uludağ University Faculty of Medicine Department of Hematology were included in the study retrospectively. The median follow-up time was 15.9 months. The median age was 66 (40-84). 8.8% of patients were ranked 2nd, 15.5% were ranked 3rd, 35.5% were ranked 4th, and 40% were ≥5th took ixazomib. Overall, 100% of patients were on PIs (bortezomib 100%, carfilzomib 31.1%), 88.8% on immunomodulatory drugs (IMID) (lenalidomide 86.6%, pomalidomide 33.3%, thalidomide 4.4%) and 55.5% also underwent autologous stem cell transplantation before the combination of ixazomib, lenalidomide, and dexamethasone (IRd). All patients received ixazomib in combination with lenalidomide and dexamethasone. The treatment was well tolerated, with a low discontinuation rate due to adverse events (6.6%). The most common side effects were cytopenia (50%) and infection (25%). The overall response rate was 77.7%, the very good partial response rate was 20%, the complete response rate was 28%, the partial response rate was 11.4%, the minimal response rate was 5.7%, the stable disease rate was 5.7%, and progressive disease rate was 28.5%. Median progression-free survival (PFS) on ixazomib treatment was 29.1 months (95% CI 17.2-40.9). PFS was 75% and 59% at 12 and 24 months, respectively. Median overall survival (OS) was 22.6 months (95% CI 18.8-30.3).; OS was 73% and 49% at 12 and 24 months, respectively. IRd is an effective, safe, and easy-to-administer regimen in real-life RRMM patients because it can be administered orally.
Kaynakça
- 1. Anderson KC. Oncogenomics to target myeloma in the bone marrow microenvironment. Clin Cancer Res. 2011;17(6):1225-33.
- 2. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continuedimprovement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122-8.
- 3. Röllig C, Knop S, Bornhäuser M. Multiple myeloma. Lancet. 2015;385(9983):2197-208.
- 4. Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70(5):1970-80.
- 5. Lee EC, Fitzgerald M, Bannerman B, et al. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin CancerRes. 2011;17(23):7313-23.
- 6. Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selectiveantitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res. 2011;17(16):5311-21.
- 7. Moreau P, Masszi T, Grzasko N, et al. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;374(17):1621-34.
- 8. Rajkumar SV. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol.2016;91(7):719-34.
- 9. Cohen YC, Magen H, Lavi N, et al. Ixazomib-based regimens for relapsed/refractory multiple myeloma: are real-world data compatible with clinical trial outcomes? A multi-site Israeliregistry study. Ann Hematol. 2020;99(6):1273-81.
- 10. Terpos E, Maouche N, Minarik J, et al. "Real World" Data onthe Efficacy and Safety of Ixazomib in Combination with Lenalidomide and Dexamethasone in Relapsed/RefractoryMultiple Myeloma: A Combined Study from the Greek, Czechand UK Databases. Blood. 2017;130(Supplement 1):3087-.
- 11. Varga G, Nagy Z, Demeter J, et al. Real World Efficacy and Safety Results of Ixazomib Lenalidomide and Dexamethasone Combination in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Ixazomib Named Patient Program. Pathol Oncol Res. 2019;25(4):1615-20.
Relaps Refrakter Multiple Myelomda Iksazomib, Lenalidomid, Deksametazon Kombinasyonu Deneyimi: Gerçek Yaşam Verisi
Öz
İlk oral proteazom inhibitörü (PI) olan iksazomib, lenalidomid ve deksametazon (IRd) ile kombinasyon halinde relaps refrakter multipl miyelomun (RRMM) tedavisi için onaylanmıştır. Bununla birlikte, klinik çalışma sonuçları her zaman gerçek dünyadaki sonuçlarla örtüşmez. Bu çalışmanın amacı, gerçek yaşamda RRMM'li hastaların tedavisi için iksazomib bazlı kombinasyon tedavisinin sonuçlarını değerlendirmektir. Çalışmaya Bursa Uludağ Üniversitesi Tıp Fakültesi Hematoloji Bilim Dalı’ndan toplam 45 RRMM tanılı hasta retrospektif olarak dahil edildi. Medyan takip süresi 15.9 ay (0.3-53.8) ve medyan yaş 66 (40-84) idi. Hastaların %8.8’i 2. sırada, % 15.5’i 3. sırada, %35.5’i 4. sırada ve %40’ı da ≥5. sırada iksazomib aldı. Genel olarak, IRd’den önce hastaların %100’ü PI (bortezomib %100, karfilzomib %31.1), %88.8’i immünomodülatör ilaç (IMID) (lenalidomid %86.6, pomalidomid %33.3, talidomid %4.4) almış ve %55.5’ine de otolog kök hücre nakli yapılmıştır. Hastaların hepsi lenalidomid ve deksametazon ile kombinasyon halinde iksazomib almıştır. Tedavi, yan etki nedenli düşük bir kesilme oranıyla (%6.6) iyi tolere edilmiştir. En sık görülen yan etkiler sitopeni (%50) ve enfeksiyon (%25) olmuştur. Genel yanıt oranı %77.7, çok iyi kısmi yanıt oranı %20, tam yanıt oranı % 28,5 kısmi yanıt oranı %11.4, minimal yanıt oranı %5.7, stabil hastalık oranı %5.7, progresif hastalık oranı %28.5 saptandı. İksazomib tedavisinde medyan progresyonsuz sağkalım (PFS) 29.1 aydı (%95 GA 17.2–40.9). PFS 12 ve 24 ayda sırasıyla %75 ve %59 idi. Medyan genel sağkalım (OS) 22.6ay (%95 GA 18.8–40.9) idi; OS 12 ve 24 ayda sırasıyla %73 ve %49 idi. Gerçek yaşamda RRMM hastalarında IRd etkili, güvenli ve oral verilebilmesi nedeniyle kolay uygulanabilir bir rejimdir.
Kaynakça
- 1. Anderson KC. Oncogenomics to target myeloma in the bone marrow microenvironment. Clin Cancer Res. 2011;17(6):1225-33.
- 2. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continuedimprovement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122-8.
- 3. Röllig C, Knop S, Bornhäuser M. Multiple myeloma. Lancet. 2015;385(9983):2197-208.
- 4. Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70(5):1970-80.
- 5. Lee EC, Fitzgerald M, Bannerman B, et al. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin CancerRes. 2011;17(23):7313-23.
- 6. Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selectiveantitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res. 2011;17(16):5311-21.
- 7. Moreau P, Masszi T, Grzasko N, et al. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;374(17):1621-34.
- 8. Rajkumar SV. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol.2016;91(7):719-34.
- 9. Cohen YC, Magen H, Lavi N, et al. Ixazomib-based regimens for relapsed/refractory multiple myeloma: are real-world data compatible with clinical trial outcomes? A multi-site Israeliregistry study. Ann Hematol. 2020;99(6):1273-81.
- 10. Terpos E, Maouche N, Minarik J, et al. "Real World" Data onthe Efficacy and Safety of Ixazomib in Combination with Lenalidomide and Dexamethasone in Relapsed/RefractoryMultiple Myeloma: A Combined Study from the Greek, Czechand UK Databases. Blood. 2017;130(Supplement 1):3087-.
- 11. Varga G, Nagy Z, Demeter J, et al. Real World Efficacy and Safety Results of Ixazomib Lenalidomide and Dexamethasone Combination in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Ixazomib Named Patient Program. Pathol Oncol Res. 2019;25(4):1615-20.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Hematoloji |
| Bölüm | Özgün Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 9 Haziran 2023 |
| Kabul Tarihi | 20 Nisan 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 49 Sayı: 1 |
Kaynak Göster
Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.