complete remission

Clinical Efficacy of Daratumumab in Monotherapy of Relapsed/Refractory Multiple Myeloma

AUTOIMMUNE THROMBOCYTOPENIA , ,

SS Bessmeltsev1, EV Karyagina2, EYu Ilyushkina2, ZhL Stolypina2, RR Miftakhova1, II Kostroma1, TL Shelkovskaya2

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

2 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

For correspondence: Prof. Stanislav Semenovich Bessmeltsev, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-67-80, +7(911)228-18-01; e-mail: bsshem@hotmail.com, bessmeltsev@yandex.ru

For citation: Bessmeltsev SS, Karyagina EV, Ilyushkina EYu, et al. Clinical Efficacy of Daratumumab in Monotherapy of Relapsed/Refractory Multiple Myeloma. Clinical oncohematology. 2020;13(1):25–32. (In Russ).

DOI: 10.21320/2500-2139-2020-13-1-25-32

ABSTRACT

Background. Daratumumab is IgG1-κ humanized anti-CD38 monoclonal antibody. It has a direct impact on tumor and immunomodulatory effect.

Aim. To assess the efficacy of daratumumab monotherapy in patients with progressive, and relapsed/refractory multiple myeloma (MM), as well as to find out the degree of toxicity and safety of this drug.

Materials & Methods. The trial included 10 MM patients (3 men and 7 women) aged 51–74 years (median 57 years). Stage 3 (according to Durie-Salmon system) was determined in all patients, in 2 of them stage 3B with creatinine clearance < 30 mL/min was reported. According to ISS (International Staging System) criteria, stage 2 and stage 3 were identified in 6 and 4 patients, respectively. All the patients had been previously treated with bortezomib and lenalidomide with further double refractoriness in 4 out of 10 patients. Bendamustine and carfilzomib were administered to one patient each, both in combined regimens. The number of previous therapy lines was 3–6 (median 5).

Results. Overall response was 50 % including 2 (20 %) patients with very good partial remission. In 1 (10 %) patient complete remission was achieved. During the follow-up of 6–32 months (median 15 months) median overall survival was not achieved. Median progression-free survival was 17.8 months. Daratumumab is characterized by favorable safety profile. In 20 % of patients infusion-induced reactions with severity grades 1–2 were observed. Among other adverse events the following should be pointed out: weakness (30 %), nausea (10 %), headache (10 %), anorexia (10 %), thrombocytopenia (20 %), and neutropenia (30 %). No serious complications were reported.

Conclusion. Daratumumab treatment is a safe and effective method of anticancer drug therapy in relapsed/refractory MM.

Keywords: daratumumab, multiple myeloma, complete remission, overall response, survival, double refractoriness.

Received: August 22, 2019

Accepted: December 10, 2019

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Management of relapsed and refractory multiple myeloma: literature review and our data. Part III

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , , , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

Abstract

Advances in treatment options for patients with multiple myeloma have made a significant impact on overall survival and have helped to achieve the rates of response and duration of remission previously not unachievable with standard chemotherapy-based approaches. These improvements are due, in a large part, to the development of the novel agents, including bortezomib, thalidomide, and lenalidomide, each of which has substantial single-agent activity. Combinations of bortezomib, thalidomide, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. However, when patients are unresponsive to immunomodulatory drugs and bortezomib, the prognosis becomes poor. A number of novel agents are being tested in multiple myeloma, but relapsed/refractory multiple myeloma still represents a challenge and difficult area for drug development. Therefore, the new agents are needed. In addition, a large number of second- or third-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. Such agents as carfilzomib, pomalidomide, vorinostat, panobinistat, romidepsin, perifosine, tanespimycin, bendamustine, and elotuzumab are just a few out of many exciting new compounds that are being tested in phases I, II, or III of clinical trials for relapsed patients. This review covers the new strategies, based on clinical trials and our own data and intended for optimizing treatment outcomes in relapsed/refractory multiple myeloma. We describe the various classes of novel drugs under investigation and discuss the pros and cons of the data obtained in preclinical and clinical studies. The adverse effects of the new drugs are presented in detail.

Keywords: multiple myeloma, relapsed/refractory multiple myeloma, bortezomib, thalidomide, lenalidomide, carfilzomib, pomalidomide, treatment, complete remission, overall survival, neuropathy.

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Multiple myeloma (management of newly diagnosed patients): literature review and our on data. Part II

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

ABSTRACT

Over the last decades, survival rates for young patients with multiple myeloma markedly increased mainly due to the use of autologous stem cell transplantation (ASCT) and new highly efficacious rescue therapies. In patients with multiple myeloma over 65 years of age, a combination of melphalan and prednisone (MP) is traditionally used. Introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors substantially changed the therapeutic approach to the disease. Many double-, triple-, and quadruple-agent combinations were studied in the patients with newly diagnosed multiple myeloma. It was established that the achievement of complete response (CR) is an independent predictor of prolonged progression-free survival (PFS) and overall survival (OS). The data from prospective trials completed suggest that the best available strategy to achieve high CR rates and prolong its duration includes an induction therapy with a triple-agent bortezomib- or IMiDs-based regimen followed by ASCT and consolidation/maintenance with IMiDs or proteasome inhibitors. The vast majority of elderly patients with MM are ineligible for ASCT. Introduction of novel agents such as thalidomide, bortezomib, or lenalidomide considerably improved the treatment outcomes. MPT (MP + thalidomide), VMP (MP + bortezomib), and MPR-R (MP + lenalidomide) regimens are currently regarded as the new standards of care for elderly patients with multiple myeloma. The prognosis for multiple myeloma is determined by numerous factors, all of which should be considered when choosing the initial therapy. This review covers the new strategies based on the current studies being conducted that are aimed at optimizing treatment outcomes in the patients with newly diagnosed multiple myeloma.

Keywords: multiple myeloma, bortezomib, thalidomide, lenalidomide, treatment, complete remission, overall survival, neuropathy, autologous stem cell transplantation

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