Anti-CD38 monoclonal antibody daratumumab enhances the overall response rate in patients with multiple myeloma

Year 2024, Volume: 17 Issue: 3, 448 - 455, 05.07.2024

Özde Elver , Nevin Alayvaz Aslan , Veysel Erol , İsmail Can Kendir , Nil Guler

https://doi.org/10.31362/patd.1427969

Abstract

Purpose: New medicines employed in recent years have resulted in significant increases in survival rates for Multiple Myeloma (MM). Daratumumab, a monoclonal antibody against CD38, is utilized in both first-line myeloma treatment and relapsed/refractory illness. Our study aims to assess the clinical features, response to treatment and factors influencing response to treatment in patients who received daratumumab monotherapy or combination therapy at our center.
Materials and methods: In the Pamukkale University Faculty of Medicine Hematology clinic between June 2022 and June 2023, 21 patients who were treated with daratumumab after receiving a multiple myeloma diagnosis were included. Demographic features of the patients, disease stage, prior therapies, characteristics of daratumumab treatment, and response rates to treatments were retrospectively analyzed.
Results: The patients median age was 65±9.7 years (42-80), with a female/male ratio of 11/10. Treatment with daratumumab: 61.9% was used after two lines of therapy, 23.8% was used in first-line therapy, and 14.28% was used in second-line therapy. The average number of cycles was 4.05±5.06. Of the patients treated with daratumumab, 4.76% were treated as a single agent; 61.9% were treated in combination with immunomodulatory medications, cyclophosphamide and/or melphalan; and 33.4% were treated in conjunction with chemotherapy. When the response to treatment was evaluated, 38.1% of the patients passed away, 38.1% had a very good partial response (VGPR) or better, and 23.8% had a partial response (PR). 42.9% of patients who received daratumumab along with chemotherapy died. With daratumumab-containing regimens, overall response rates increased significantly as the number of cycles increased (ORR) (p=0.026).
Conclusion: When daratumumab-containing protocols are used in the treatment of multiple myeloma, it has been observed that overall response rates improve and treatment success increases in direct proportion to the number of cures.

Keywords

Daratumumab, multiple myeloma, treatment

Ethical Statement

Pamukkale University's Non-Interventional Clinical Research Ethics Committee approved the study on June 13, 2022, with the reference number 168199.

Multipl miyelomda Anti-CD38 monoklonal antikoru daratumumab tedavisi genel yanıt oranını arttırır

Abstract

Amaç: Son yıllarda kullanılan yeni ilaçlar Multipl Miyelom (MM) hastalığında sağkalım oranlarında önemli artışlara yol açmıştır. CD38’e karşı geliştirilmiş monoklonal antikor olan Daratumumab hem birinci basamak miyelom tedavisinde hem de nükseden/dirençli hastalıkta kullanılmaktadır. Çalışmamız, merkezimizde daratumumab monoterapisi veya kombinasyon tedavisi alan hastaların klinik özelliklerini, tedaviye yanıt ve yanıtı etkileyen faktörleri değerlendirmeyi amaçlamaktadır.
Gereç ve yöntem: Pamukkale Üniversitesi Tıp Fakültesi Hematoloji kliniğinde Haziran 2022 ile Haziran 2023 tarihleri arasında multipl miyelom tansı ile takip edilen ve daratumumab tedavisi alan 21 hasta çalışmaya dahil edildi. Hastaların demografik özellikleri, evreleri, daha önce aldıkları tedaviler, daratumumab tedavisinin özellikleri ve tedaviyle elde edilen yanıt oranları retrospektif olarak incelendi.
Bulgular: Hastaların ortanca yaşı 65±9,7 yıl (42-80), kadın/erkek oranı 11/10 idi. Daratumumab tedavisi hastaların %61,9’da iki basamak tedavi sonrasında, %23,8’inde birinci basamak tedavide ve %14,28’de ikinci basamak tedavide kullanıldı. Ortalama siklus sayısı 4,05±5,06 idi. Daratumumab ile tedavi edilen hastaların %4,76’sında tek ajan, %61,9’u immünomodülatör ilaçlar, siklofosfamid ve/veya melfalan ile kombinasyon halinde ve %33,4’ü ise kemoterapi ile kombinasyon halinde kullanıldı.
Tedaviye yanıt değerlendirildiğinde; hastaların %38,1'inin kaybedildiği, %38,1'inin çok iyi kısmi yanıt (ÇİKY) ve üzeri yanıt ile %23,8'inin stabil hastalık (SH) ile tedaviye devam ettiği görüldü. Kemoterapiyle birlikte daratumumab alan hastaların %42,9’u kaybedildi. Daratumumab içeren rejimler ile kür sayısı arttıkça genel yanıt oranlarının anlamlı bir şekilde arttığı görüldü (p=0,026).
Sonuç: Multiple miyelom tedavisinde daratumumab içeren protokoller kullanıldığında kür sayısı ile doğru orantılı olarak genel yanıt oranlarının iyileştiği ve tedavi başarısının arttığı görülmüştür.

Keywords

Daratumumab, multiple miyelom, tedavi

Ethical Statement

Pamukkale Üniversitesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurulu, çalışmayı 13 Haziran 2022 tarihinde 168199 referans numarasıyla onayladı.

References

• 1. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol 2022;97:1086-1107. https://doi.org/10.1002/ajh.26590
• 2. Overdijk MB, Verploegen S, Bögels M, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs 2015; 7:311-321. https://doi.org/10.1080/19420862.2015.1007813
• 3. De Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 2011;186:1840-1848. https://doi.org/10.4049/jimmunol.1003032
• 4. Van der Veer MS, de Weers M, van Kessel B, et al. Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica 2011;96:284-290. https://doi.org/10.3324/haematol.2010.030759
• 5. Usmani SZ, Weiss BM, Plesner T, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood 2016:128:37-44. https://doi.org/10.1182/blood-2016-03-705210
• 6. Mateos MV, Sonneveld P, Hungria V, et al. Daratumumab, bortezomib, and dexamethasone versus bortezomib and dexamethasone in patients with previously treated multiple myeloma: three-year follow-up of CASTOR. Clin Lymphoma Myeloma Leuk 2020;20:509-518. https://doi.org/10.1016/j.clml.2019.09.623
• 7. Bahlis NJ, Dimopoulos MA, White DJ, et al. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia 2020;34:1875-1884. https://doi.org/10.1038/s41375-020-0711-6
• 8. Moreau P, Attal M, Hulin C, 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;394:29-38. https://doi.org/10.1016/S0140-6736(19)31240-1
• 9. Mateos MV, Cavo M, Blade J, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet 2020;395:132-141. https://doi.org/10.1016/S0140-6736(19)32956-3
• 10. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538-548. https://doi.org/10.1016/S1470-2045(14)70442-5 11. Common terminology criteria for adverse events (CTCAE) v5.0. 2017;27:1-155.
• 12. Zhou X, Ruckdeschel A, Peter J, et al. Salvage therapy with "Dara-KDT-P(A)CE" in heavily pretreated, high-risk, proliferative, relapsed/refractory multiple myeloma. Hematol Oncol 2022;40:202-211. https://doi.org/10.1002/hon.2949
• 13. Saltarella I, Desantis V, Melaccio A, et al. Mechanisms of resistance to Anti-CD38 daratumumab in multiple myeloma. Cells 2020;9:167. https://doi.org/10.3390/cells9010167
• 14. Nijhof IS, Casneuf T, van Velzen J, et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood 2016;128:959-970. https://doi.org/10.1182/blood-2016-03-703439