The Efficacy of Bortezomib, Lenalidomide, and Dexamethasone Combination as Induction Therapy in Patients with Multiple Myeloma Complicated by the End-Stage Renal Disease

AIM. To analyze our own experience in the use of the VRd regimen in the induction therapy for patients with newly diagnosed multiple myeloma (MM) complicated by the end-stage renal disease (ESRD).

MATERIALS & METHODS. This prospective cohort trial enrolled 15 newly diagnosed MM patients with ESRD (eGFR < 15 mL/min/1.73 m²) in the period from February to October 2019. Six original RVd induction cycles were planned: lenalidomide 25 mg per os on Days 1, 4, 8, 11, and 15 (administered after hemodialysis), bortezomib 1.3 mg/m² subcutaneously on Days 1, 4, 8, and 11, as well as dexamethasone 20 mg per os or IV on Days 1, 2, 4, 5, 8, 9, 11, and 12. Blood sampling for pharmacokinetic analysis was performed in 5 (33 %) patients prior to therapy (end-point 0) as well as 4, 24, and 96 hours after the first lenalidomide dose during the 1st RVd cycle.

RESULTS. The median age of patients was 67 years (range 55–74 years); there were 9 women and 6 men. All of them were hemodialysis-dependent. The median GFR was 6.3 (5.7; 12.5) mL/min/1.73 m². In all patients, the serum β2-microglobuline concentration was > 5.5 mg/L (ISS III = 100 %). In 4 (26.7 %) out of 15 patients, renal response was achieved (group I), whereas 11 (73.3 %) patients showed no renal recovery and remained hemodialysis-dependent (group II). Overall (hematologic) response was 80 % (CR 26.7 %, VGPR 20 %, PR 33.3 %). With the median follow-up of 4.64 years, the 5-year overall survival (OS) in all 15 patients was 33.3 ± 12.2 %. In group I (n = 4), life expectancy of patients was 4.45+, 1.81, 4.93+, and 4,68+ years. Out of them, 3 patients are being further followed-up, one died. In group II (n = 11; 9 events), the median OS was 1.75 years. The median maximum serum lenalidomide concentration as reported 4 hours after the first dose of the drug administration was 470 (364; 496) ng/mL. After 24 hours, the lenalidomide concentration decreased 5.7-fold to 82 (54; 269) ng/mL.

CONCLUSION. The proposed original VRd regimen ensures high rates of overall response (80 %) and deep remissions (³ VGPR 46.7 %). The originality of the VRd regimen consisted in intermittent administration of 25 mg lenalidomide on Days 1, 4, 8, 11, and 15 after hemodialysis reaching a cumulative dose of 125 mg per 21-day cycle. The maximum lenalidomide concentration (C_max) did not exceed that in patients with normal renal function and gradually decreased by the next hemodialysis session and the next drug administration. The incidence and severity of adverse events did not exceed those resulting from similar regimens for treatment of hemodialysis-dependent MM patients with ESRD.

• Sergei Vyacheslavovich Semochkin NI Pirogov Russian National Research Medical University, 1 Ostrovityanova ul., Moscow, Russian Federation, 117997; PA Gertsen Moscow Oncology Research Institute, branch of the NMRC of Radiology, 3 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284 ; ФГАОУ ВО «РНИМУ им. Н.И. Пирогова» Минздрава России, ул. Островитянова, д. 1, Москва, Российская Федерация, 117997; МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2-й Боткинский пр-д, д. 3, Москва, Российская Федерация, 125284 https://orcid.org/0000-0002-8129-8114 (unauthenticated)
• E.I. Zhelnova Moscow City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 8 korp. 2 Trubetskaya ul., Moscow, Russian Federation, 119048 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Трубецкая, д. 8, стр. 2, Москва, Российская Федерация, 119048 https://orcid.org/0000-0002-0343-9348 (unauthenticated)
• V.I. Kazey Exacte Labs Bioanalytical Laboratory, 20 korp. 2 Nauchnyi pr-d, Moscow, Russian Federation, 117246 ; Биоаналитическая лаборатория «Экзактэ Лабс», Научный пр-д, д. 20, стр. 2, Москва, Российская Федерация, 117246 https://orcid.org/0000-0003-2032-6289 (unauthenticated)
• A.V. Cherkasova SM Clinic, 22 Simferopolskii b-r, Moscow, Russian Federation, 117452 ; ООО «СМ-Клиника», Симферопольский б-р, д. 22, Москва, Российская Федерация, 117452 https://orcid.org/0000-0002-5983-4953 (unauthenticated)
• A.G. Nikiforova Exacte Labs Bioanalytical Laboratory, 20 korp. 2 Nauchnyi pr-d, Moscow, Russian Federation, 117246 ; Биоаналитическая лаборатория «Экзактэ Лабс», Научный пр-д, д. 20, стр. 2, Москва, Российская Федерация, 117246 https://orcid.org/0000-0002-5719-0787 (unauthenticated)
• N.F. Frolova Moscow City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; AI Evdokimov Moscow State University of Medicine and Dentistry, 20 Delegatskaya ul., Moscow, Russian Federation, 127243 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; Московский государственный медико-стоматологический университет им. А.И. Евдокимова Минздрава России, ул. Делегатская, д. 20, Москва, Российская Федерация, 127243 https://orcid.org/0000-0002-6086-5220 (unauthenticated)
• E.A. Baryakh Moscow City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 8 korp. 2 Trubetskaya ul., Moscow, Russian Federation, 119048; Russian Medical Academy of Postgraduate Education, 2/1 Barrikadnaya ul., Moscow, Russian Federation, 125993 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Трубецкая, д. 8, стр. 2, Москва, Российская Федерация, 119048; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, ул. Баррикадная, д. 2/1, Москва, Российская Федерация, 125993 https://orcid.org/0000-0001-6880-9269 (unauthenticated)
• K.V. Yatskov Moscow City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182 https://orcid.org/0000-0003-0125-9068 (unauthenticated)
• E.A. Karimova Moscow City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182 https://orcid.org/0000-0001-7603-1741 (unauthenticated)
• O.N. Kotenko Moscow City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182 https://orcid.org/0000-0001-8264-7374 (unauthenticated)
• E.N. Misyurina Moscow City Clinical Hospital No. 52, 3 Pekhotnaya ul., Moscow, Russian Federation, 123182; IM Sechenov First Moscow State Medical University, 8 korp. 2 Trubetskaya ul., Moscow, Russian Federation, 119048 ; ГБУЗ «Городская клиническая больница № 52 ДЗМ», ул. Пехотная, д. 3, Москва, Российская Федерация, 123182; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет) Минздрава России, ул. Трубецкая, д. 8, стр. 2, Москва, Российская Федерация, 119048 https://orcid.org/0000-0003-2419-4850 (unauthenticated)

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