Evolution of Anti-Cancer Treatment and its Impact on Surrogate Prognostic Factors in Multiple Myeloma

Aim. To assess prognostic value of surrogate clinical and laboratory markers in current therapy of multiple myeloma (MM).

Materials & Methods. The analysis included 567 patients (215 men and 352 women), the Kirov region inhabitants with newly diagnosed MM over the period from January 1, 1994 to December 31, 2016. The median age was 64 years (range 29–90). Patients were divided into two groups: the first group received treatment from 1994 to 2005 (n = 269), the second group received treatment from 2006 to 2016 (n = 298). Impact of factors on overall survival (OS) was evaluated by multivariate logistic regression analysis using the Cox method.

Results. Over the period from 2006 to 2016 the number of patients treated with traditional chemotherapy decreased from 78.4 to 32.5 %. At the same time the number of patients treated with bortezomib-based regimens increased from 1.9 to 56.3 % and autologous hematopoietic stem cell transplantation (auto-HSCT) protocols — from 1.4 to 14.0 %. Median OS over the period from 1994 to 2005 was 27 months. It increased to 55 months in the period of 2006–2016. In the reference decades 5-year overall survival increased from 21 % (95% confidence interval [95% CI] 17–27 %) to 47 % (95% CI 39–55 %), respectively (hazard ratio [HR] 0.51; 95% CI 0.41–0.64; p < 0,0001). In patients treated with bortezomib-based regimens over the period from 2006 to 2016 median OS increased to 73 months compared to 27 months in 1994–2005. In patients aged ≤ 65 years and treated with auto-HSCT median OS was not reached, and median OS in patients without auto-HSCT treatment was 54 months.

Conclusions. Surrogate prognostic markers, such as the age over 65, hemoglobin level < 100 g/L, β2-microglobulin ≥ 6 mg/L, serum creatinine ≥ 177 µmol/L and stage III according to ISS and Durie-Salmon, are unfavourable predictors of survival of MM patients.

• Aleksandr Sergeevich Luchinin Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027 ; ФГБУН «Кировский НИИ гематологии и переливания крови ФМБА», ул. Красноармейская, д. 72, Киров, Российская Федерация, 610027
• S.V. Semochkin NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997 ; ФГБОУ ВО «Российский национальный исследовательский университет им. Н.И. Пирогова» Минздрава России, ул. Островитянова, д. 1, Москва, Российская Федерация, 117997
• N.V. Minaeva Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027 ; ФГБУН «Кировский НИИ гематологии и переливания крови ФМБА», ул. Красноармейская, д. 72, Киров, Российская Федерация, 610027
• N.M. Pozdeev Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027 ; ФГБУН «Кировский НИИ гематологии и переливания крови ФМБА», ул. Красноармейская, д. 72, Киров, Российская Федерация, 610027
• I.V. Paramonov Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027 ; ФГБУН «Кировский НИИ гематологии и переливания крови ФМБА», ул. Красноармейская, д. 72, Киров, Российская Федерация, 610027

1. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2016;61(1, прил. 2):1–24. doi: 10.18821/0234-5730-2016-61-1(Прил.2).[Mendeleeva OP, Votyakova OM, Pokrovskaya OS, et al. National clinical recommendations in diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2016;61(1, Suppl. 2):1–24. doi: 10.18821/0234-5730-2016-61-1(Прил.2). (In Russ)]
2. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: МК, 2016. 504 с.[Bessmel’tsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: MK Publ.; 2016. 504 p. (In Russ)]
3. Ghobrial IM, Landgren O. How I treat smoldering multiple myeloma. Blood. 2014;124(23):3380–8. doi: 10.1182/blood-2014-08-551549. DOI: https://doi.org/10.1182/blood-2014-08-551549
4. Hsu P, Lin TW, Gau JP, et al. Risk of early mortality in patients with newly diagnosed multiple myeloma. Medicine. 2016;94(50):e2305. doi: 1097/MD.0000000000002305. DOI: https://doi.org/10.1097/MD.0000000000002305
5. Pulte D, Jansen L, Castro FA, et al. Trends in survival of multiple myeloma patients in Germany and the United States in the first decade of the 21st century. Br J Haematol. 2015;171(2):189–96. doi: 10.1111/bjh.13537. DOI: https://doi.org/10.1111/bjh.13537
6. Libby E, Garcia D, Quintana D, et al. Disease-specific survival for patients with multiple myeloma: significant improvements over time in all age groups. Leuk Lymphoma. 2014;55(12):2850–7. doi: 10.3109/10428194.2014.89770 DOI: https://doi.org/10.3109/10428194.2014.897700
7. Митина Т.А., Голенков А.К., Трифонова Е.В. и др. Эффективность леналидомида, бортезомиба и преднизолона при лечении пациентов с рецидивирующей и рефрактерной множественной миеломой. Онкогематология. 2015;4(10):8–14. doi: 10.17650/1818-8346-2015-10-4-8-14.[Mitina TA, Golenkov AK, Trifonova EV, et al. Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma. Oncohematology. 2015;4(10):8–14. doi: 10.17650/1818-8346-2015-10-4-8-14. (In Russ)] DOI: https://doi.org/10.17650/1818-8346-2015-10-4-8-14
8. Hungria VTМ, Maiolino A, Martinez G, et al. Confirmation of the utility of the International Staging System and identification of a unique pattern of disease in Brazilian patients with multiple myeloma. Haematologica. 2008;93(5):791–2. doi: 10.3324/haematol.11637. DOI: https://doi.org/10.3324/haematol.11637
9. Lu J, Lu J, Liu A, et al. The applicability of the International Staging System in Chinese patients with multiple myeloma receiving bortezomib or thalidomide-based regimens as induction therapy: a multicenter analysis. Biomed Res Int. 2015;2015:1–7. doi: 10.1155/2015/856704. DOI: https://doi.org/10.1155/2015/856704
10. Dosani T, Covut F, Beck R, et al. Significance of the absolute lymphocyte/monocyte ratio as a prognostic immune biomarker in newly diagnosed multiple myeloma. Blood Cancer J. 2017;7(6):e579. doi: 10.1038/bcj.2017.60. DOI: https://doi.org/10.1038/bcj.2017.60
11. Hanbali A, Hassanein M, Rasheed W, et al. The evolution of prognostic factors in multiple myeloma. Adv Hematol. 2017;2017:1–11. doi: 10.1155/2017/4812637. DOI: https://doi.org/10.1155/2017/4812637
12. Chng WJ, Dispenzieri A, Chim CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28(2):269–77. doi: 10.1038/leu.2013.247. DOI: https://doi.org/10.1038/leu.2013.247
13. Rajkumar SV, Kumar S. Multiple Myeloma: diagnosis and treatment. Mayo Clin Proc. 2016;91(1):101–18. doi: 10.1016/j.mayocp.2015.11.007. DOI: https://doi.org/10.1016/j.mayocp.2015.11.007
14. Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for multiple myeloma: a report from IMWG. J Clin Oncol. 2015;33(26):2863–6. doi: 10.1200/JCO.2015.61.2267. DOI: https://doi.org/10.1200/JCO.2015.61.2267