renal failure

Practical Aspects of the Use of Carfilzomib in Multiple Myeloma

NOVEL DRUGS , , , , ,

SV Semochkin1,2, GN Salogub3, SS Bessmeltsev4, KD Kaplanov5

1 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

2 Municipal Clinical Hospital No. 52, 3 Pekhotnaya str., Moscow, Russian Federation, 123182

3 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

4 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

5 Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

For correspondence: Prof. Sergei Vyacheslavovich Semochkin, MD, PhD, 3 Pekhotnaya str., Moscow, Russian Federation, 123182; Tel./fax: +7(495)369-00-36; e-mail: semochkin_sv@rsmu.ru

For citation: Semochkin SV, Salogub GN, Bessmeltsev SS, Kaplanov KD. Practical Aspects of the Use of Carfilzomib in Multiple Myeloma. Clinical oncohematology. 2019;12(1):21–31.

DOI: 10.21320/2500-2139-2019-12-1-21-31

ABSTRACT

Carfilzomib (Kyprolis®, Amgen), a second-generation proteasome inhibitor, is capable of covalent bonding and irreversible inhibition of the 20S proteasome chymotrypsin-like activity. In 2016 this drug was approved in Russia for monotherapy of relapsed refractory multiple myeloma (MM) and in combination with lenalidomide and dexamethasone (KRd) or only with dexamethasone (Kd) for treatment of patients with relapsed MM after at least one line of prior therapy. The present review outlines mechanism, clinical efficacy, and adverse effects of carfilzomib according to the data of a phase II (monotherapy) trial and two key randomized phase III (carfilzomib combined with other drugs) trials. The ASPIRE trial demonstrated that adding carfilzomib to the combination of lenalidomide and dexamethasone (KRd) significantly improves progression-free survival (PFS) compared with the Rd original regimen (median 26.3 vs. 17.6 months; hazard ratio [HR] 0.69; p = 0.0001). Median overall survival (OS) was 48.3 months (95% confidence interval [95% CI] 42.4–52.8 months) for KRd vs. 40.4 months (95% CI 33.6–44.4 months) for Rd (HR 0.79; p = 0.0045). The ENDEAVOR trial showed that as compared with combination of bortezomib and dexamethasone (Vd) the carfilzomib + dexamethasone (Kd) regimen significantly improves PFS (median 18.7 vs. 9.4 months; HR 0.53; p < 0.0001) and OS (47.6 vs. 40.0 months; HR 0.79; p = 0.010) as well. The present review also discusses how carfilzomib is to be used in special patient groups (with renal failure and high cytogenetic risk).

Keywords: carfilzomib, proteasome inhibitor, lenalidomide, bortezomib, multiple myeloma, renal failure, cytogenetic risk.

Received: May 12, 2018

Accepted: December 28, 2018

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The Use of Pomalidomide in the Treatment of Relapsed/Refractory Multiple Myeloma in Patients with Renal Failure

NOVEL DRUGS , ,

IG Rekhtina, MV Nareiko, LP Mendeleeva

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Irina Germanovna Rekhtina, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-49-66; e-mail: rekhtina.i@blood.ru

For correspondence: Rekhtina IG, Nareiko MV, Mendeleeva LP. The Use of Pomalidomide in the Treatment of Relapsed/Refractory Multiple Myeloma in Patients with Renal Failure. Clinical oncohematology. 2018;11(4):283–7.

DOI: 10.21320/2500-2139-2018-11-4-283-287

ABSTRACT

The present review includes data on efficacy and safety of pomalidomide, an immunomodulating 3rd generation drug used for treatment of relapsed and refractory multiple myeloma patients with renal failure. The results of multicenter randomized trials proved similar efficacy and comparable safety profile in patients with normal renal function and patients with moderate and/or severe renal failure. All patients received the standard starting dose. Pomalidomide dose needs to be reduced in response to hematological toxicity. The paper provides practical guidelines on the use of pomalidomide and treatment of adverse events adopted by consensus of international experts. Current approaches to multiple myeloma with renal failure, and the use of pomalidomide in particular, are demonstrated by means of a clinical case.

Keywords: multiple myeloma, pomalidomide, renal failure.

Received: March 28, 2018

Accepted: July 16, 2018

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  7. Siegel DS, Weisel KC, Dimopoulosc MA, et al. Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials. Leuk Lymphoma. 2016:57(12):2833–8. doi: 10.1080/10428194.2016.1177181.

  8. Matous J, Siegel DS, Lonial S, et al. A Phase 1 Study of the Pharmacokinetics (PK) and Safety of Pomalidomide + Low Dose Dexamethasone (POM+LODEX) in Patients (PTS) With Relapsed or Refractory Multiple Myeloma (RRMM) and Renal Impairment (RI). Clin Lymph Myel Leuk. 2015;15:e265. doi: 10.1016/j.clml.2015.07.557.

  9. Sonneveld P, Dimopoulos M, Ramasamy K, et al. Treatment (Tx) With Pomalidomide (POM) and Low-Dose Dexamethasone (LoDEX) in Patients (Pts) With Relapsed or Refractory Multiple Myeloma (RRMM) and Renal Impairment (RI) Including Those on Dialysis. Clin Lymph Myel Leuk. 2015;15:e265. doi: 10.1016/j.clml.2015.07.556.

  10. Weisel K, Dimopoulos M, Van de Donk N, et al. Phase 2 Multicenter Study of Pomalidomide (POM) Plus Low-Dose Dexamethasone (LoDEX) in Patients (Pts) With Relapsed/Refractory Multiple Myeloma (RRMM) and Renal Impairment (RI): An Updated Safety Analysis. Clin Lymph Myel Leuk. 2017;17(1):e145. doi: 10.1016/j.clml.2017.03.261.

  11. Sonneveld P, Weisel K, Van de Donk N et al. MM-013 phase 2 multicenter study of pomalidomide plus low-dose dexamethasone in patients with RRMM and renal impairment. 22nd Congress of the European Hematology Association (EHA). 2017. Abstract P343.

  12. Li Y, Wang X, O’Mara E, et al. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function. Clin Pharmacol Adv Appl. 2017;9:133–45. doi: 10.2147/CPAA.S144606.

  13. Dimopoulos M, Leleu X, Palumbo A, et al. Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma. Leukemia. 2014;28(8):1573–85. doi: 10.1038/leu.2014.60.

New Aspects of Pathophysiology and Pathomorphology of Renal Lesions in Malignant Tumors

LYMPHOID TUMORS , , , , , ,

B.T. Dzhumabaeva, L.S. Biryukova

Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Boldukyz Tolgonbaevna Dzhumabaeva, DSci, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)613-24-68; e-mail: bola.blood@yandex.ru

For citation: Dzhumabaeva BT, Biryukova LS. New Aspects of Pathophysiology and Pathomorphology of Renal Lesions in Malignant Tumors. Clinical oncohematology. 2015;8(4):390–396 (In Russ).

DOI: 10.21320/2500-2139-2015-8-4-390-396

ABSTRACT

Glomerular injuries associated with malignancy are rare and they are morphologically heterogeneous. Although the pathophysiologic interrelations between a tumor and glomerulopathy are not clear, molecular mechanisms of paraneoplastic glomerulopathies and pathologic features of renal lesions in solid tumors, lymphoproliferative and myeloproliferative disorders have been discovered over recent decades.

Keywords: membranous nephropathy, immunotactoid glomerulopathy, minimal-change glomerulopathy, fibrillary glomerulonephritis, renal failure, anti-PLA2R1 antibody, c-mip protein.

Received: March 19, 2015

Accepted: October 23, 2015

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Chronic lymphocytic leukemia and renal cell carcinoma: literature review and case reports

DIAGNOSIS AND TREATMENT OF LYMPHOID TUMORS , , ,

B.T. Dzhumabaeva, E.A. Nikitin, I.B. Kaplanskaya, E.E. Zybunova, L.S. Biryukova,

FSBI «Haematological Research Center» Russian Ministry of Health, Moscow, Russian Federation

ABSTRACT

Renal cell carcinoma which had acceded to the CLL, induces the progression of lymphatic tumours and contributes to the rapid development of renal failure. The surgical removal of the affected renal not eliminates the progression of CLL. Monotherapy by alkylating agents is not effective, while bendamustine therapy allows to reach the positive result.

Keywords: Chronic lymphocytic leukemia (CLL), Renal cell carcinoma, renal failure, bendamustine.

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