Results Of Monotherapy And Combination Treatment Of Daratumumab In Relapsed Refractory Multiple Myeloma - Single Center Experience

Abstract

Objective: With the addition of proteasome inhibitors and immunomodulators to multiple myeloma treatment protocols in recent years, the response rates have improved considerably, but in relaps refractory patients treatment options are still limited and survival is short. Daratumumab is a human CD38 monoclonal antibody and has achieved a very good response in both monotherapy and combination therapies. Although it has been proven effective in clinical studies, the literature information of daratumumab obtained from real-life data, is very limited for our country. Therefore we aimed to examine the characteristics and response rates of patients who were treated with daratumumab in our center. Materials and Methods: Files of 10 patients treated with daratumumab, were analyzed retrospectively. Data containing demographics and response rates were evoluated in the light of literature. Results: Mean age at diagnosis of patients was 58 years. Median follow-up time was 58.3 months and median duration of daratumumab treatment was 3.9 months. The median overall response rate was 40%. All patients with at least partial response were taking the Dara-Bor-Dex combination. Totally 60% of patients were alive. Median time from daratumumab to death was 35 days. Conclusion: In our study, similar with the literature, response rates were improved with daratumumab in the treatment of relapsed refractory myeloma

Keywords

• Daratumumab
• multiple myeloma
• Survival.

Relaps refrakter multiple myelomda daratumumabın tekli ve kombine tedavi sonuçları-tek merkez deneyimi

Abstract

Giriş ve Amaç: Son yıllarda multipl miyelom tedavi protokollerine proteazom inhibitörleri ve immünomodülatörlerin eklenmesiyle, yanıt oranları önemli ölçüde iyileşmiştir, ancak relaps refrakter hastalarda tedavi seçenekleri hala sınırlıdır ve sağkalım kısadır. Daratumumab, bir insan CD38 monoklonal antikorudur ve hem monoterapi ile hem de kombinasyon terapilerinde çok iyi bir yanıt elde etmiştir. Klinik çalışmalarda etkinliği kanıtlanmış olmasına rağmen, daratumumabın gerçek yaşam verilerinden elde edilen literatür bilgileri ülkemizde oldukça sınırlıdır. Bu nedenle merkezimizde daratumumab ile tedavi edilen hastaların karakteristik özelliklerini ve yanıt oranlarını incelemeyi amaçladık. Gereç ve Yöntemler: : Daratumumab ile tedavi edilen 10 hastanın dosyaları geriye dönük olarak incelendi. Demografik bilgileri ve yanıt oranlarını içeren veriler literatür ışığında geliştirildi. Bulgular: Hastaların ortalama tanı yaşı 58 idi. Medyan takip süresi 58,3 ay ve medyan daratumumab tedavi süresi 3,9 aydı. Medyan genel yanıt oranı % 40 idi. En az kısmi yanıt alınan tüm hastalar dara-bor-dex kombinasyonu alıyordu. Hastaların toplam % 60'ı hayattaydı. Daratumumabdan ölüme kadar geçen medyan süre 35 gündü. Sonuç: Çalışmamızda relaps refrakter miyelom tedavisinde daratumumab ile literatür ile benzer şekilde olumlu yanıt oranları saptandı.

Keywords

• Multiple myelom
• daratumumab
• sağkalım

Supporting Institution

Yok

References

1. Hahalis, G, Kourakli, A, Gerasimidou, I, Kalogeropoulos, A.P, Sitafidis, G, Papageorgiou, U, et al. Cardiac mortality in {beta}-thalassemia major: resting but not dobutamine stress echocardiography predicts mortality among initially cardiac disease-free patients in a prospective 12-year study. European Journal of Heart Failure, 2009,11(12), 1178-81.
2. Malavasi, F, Deaglio, S, Funaro, A, Ferrero, E, Horenstein, A.L, Ortolan, E, et al., Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology, Physiology Reviews. 2008,88(3):841-86.
3. Dima, D, Dower, J, Comenzo, R.L, Varga, C, Evaluating Daratumumab in the Treatment of Multiple Myeloma: Safety, Efficacy and Place in Therapy, Cancer Managment Research, 2020, 12, 7891-903.
4. Lonial, S, Weiss, B.M, Usmani, S.Z, Singhal, S, Chari, A, Bahlis, N.J, et al., Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial, Lancet, 2016, 387(10027), 1551-60.
5. Usmani, S.Z, Nahi, H, Mateos, M.V, van de Donk, N, Chari, A, Kaufman, J.L, et al., Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma, Blood, 2019, 134(8), 668-77.
6. Usmani, S.Z, Weiss, B.M, Plesner. T, Bahlis. N.J, Belch. A, Lonial, S, et al., Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood, 2016,128(1),37-44.
7. Mateos, M.V, Sonneveld, P, Hungria, V, Nooka, A.K, Estell, J.A, Barreto, W, et al., Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR, Clinical Lymphoma Myeloma Leukemia. 2020, 20(8), 509-18.
8. Moreau, P, Attal, M, Hulin, C, Arnulf, B, Belhadj, K, Benboubker, L, et al., Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study, Lancet, 2019, 394(10192), 29-38.

9. Dimopoulos, M.A, Oriol, A, Nahi,, H, San-Miguel J, Bahlis, N.J, Usmani, S.Z, et al., Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma, New England Journal of Medicine. 2016, 375(14), 1319-31.
10. Beksac, M, Aydin, Y, Goker, H, Turgut, M, Besisik, S.K, Cagirgan, S, et al., Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma, Clinical Lymphoma Myeloma Leukemia, 2020, 20(8), e474-e84.
11. Siegel, D.S, Schiller, G.J, Samaras, C, Sebag, M, Berdeja, J, Ganguly, S, et al., Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment, Leukemia, 2020, 34(12), 3286-97.
12. Dimopoulos, M, Quach, H, Mateos, M.V, Landgren, O, Leleu, X, Siegel, D, et al., Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study, Lancet, 2020, 396(10245), 186-97.
13. Stege, C.A.M, Nasserinejad, K, Levin, M-D, Thielen, N, Klein, S.K, Ludwig, I, et al., Efficacy and Tolerability of Ixazomib, Daratumumab and Low Dose Dexamethasone (IDd) in Unfit and Frail Newly Diagnosed Multiple Myeloma (NDMM) Patients; First Interim Safety Analysis of the Phase II HOVON 143 Study, Blood, 2018, 132(Supplement 1), 596.