Carfilzomib, lenalidomide and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience

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Abstract

Background. Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial.

Aim. Analysis of efficacy and safety of KRd in routine clinical practice.

Materials and methods. The prospective analysis included patients with MM who received at least one line of previous therapy. The inclusion criteria were relapse/progression; refractoriness; lack of very good partial response (VGPR) and more after the first line of therapy. Since February 2016, we used KRd like in ASPIRE trial, since October 2019, carfilzomib has been used at a dose of 56 mg/m2 on days 1, 8 and 15. Autologous hematopoietic stem cell transplantation (autoHSCT), consolidation (KRd) and maintenance therapy (Rd) were regarded as one line of therapy.

Results and discussion. We evaluated 77 patients with median age at the time of diagnosis is 55 (30–72) years. For 56% (n=43) of patients KRd was applied as the second line (group 1), for 44% (n=34) – as the third and more (group 2). In 23/43 patients from group 1, an early change in therapy was made due to insufficient effectiveness (after 2–4 courses of VCD or PAD). KRd served as a "bridge" to autoHSCT in 25 (32%) patients (21 of 25 in group 1). Another 7 patients underwent collection of autoHSC (all from group 1).

The overall response rate (ORR) was 80.5%, with 33.8% complete response (CR) and 26% VGPR. ORR in group 1 was 98% versus 65.6% in group 2; 24-month overall survival (OS) was 70%, progression free survival (PFS) – 49.8%. In group 1, 24-month OS was 85.6% versus 50.0% in group 2, 24-month PFS was 67.8% versus 25.5% (p=0.01).

Conclusion. Our analysis confirmed the high efficiency of KRd in the treatment of RRMM in real-life practice. Early correction of therapy with insufficient effectiveness of the first line made it possible to implement the strategy of high-dose consolidation and autoHSCT in a larger percentage of patients with MM.

About the authors

Vera A. Zherebtsova

Botkin City Clinical Hospital

Author for correspondence.
Email: vera_ger@mail.ru
ORCID iD: 0000-0002-3052-269X

канд. мед. наук, врач-гематолог отд-ния трансплантации костного мозга и гемопоэтических стволовых клеток №56

Russian Federation, Moscow

Vladimir I. Vorobyev

Botkin City Clinical Hospital

Email: vera_ger@mail.ru
ORCID iD: 0000-0002-2692-8961

канд. мед. наук, врач-гематолог, зав. отд-нием трансплантации костного мозга и гемопоэтических стволовых клеток №56

Russian Federation, Moscow

Eduard G. Gemdzhian

National Research Center for Hematology

Email: vera_ger@mail.ru
ORCID iD: 0000-0002-8357-977X

ст. науч. сотр. лаб. биостатистики

Russian Federation, Moscow

Margarita A. Ulyanova

Botkin City Clinical Hospital

Email: vera_ger@mail.ru
ORCID iD: 0000-0003-4977-1482

врач-гематолог отд-ния трансплантации костного мозга и гемопоэтических стволовых клеток №56

Russian Federation, Moscow

Mikhail V. Chernikov

Research Institute of Health Organization and Medical Management

Email: vera_ger@mail.ru
ORCID iD: 0000-0002-7869-209X

программист организационно-методического отд. по гематологии

Russian Federation, Moscow

Valentina L. Ivanova

Botkin City Clinical Hospital

Email: vera_ger@mail.ru
ORCID iD: 0000-0001-9272-1742

врач-гематолог, зав. клинико-диагностическим отд-нием 

Russian Federation, Moscow

Olga Yu. Vinogradova

Botkin City Clinical Hospital

Email: vera_ger@mail.ru
ORCID iD: 0000-0002-3669-0141

д-р мед. наук, врач-гематолог, зав.

Russian Federation, Moscow

Vadim V. Ptushkin

Botkin City Clinical Hospital

Email: vera_ger@mail.ru
ORCID iD: 0000-0002-9368-6050

д-р мед. наук, врач-гематолог, зам. глав. врача по медицинской части (гематологии)

Russian Federation, Moscow

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Distribution of patients' age at the beginning of KRd therapy (n=77), %.

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3. Fig. 2. Maximum antitumor response to the KRd therapy lines in 2 groups.

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4. Fig. 3. Overall survival (OS) in patients with multiple myeloma (MM) on KRd therapy.

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5. Fig. 4. Progression-free survival (PFS ) in patients with MM (n=77) on KRd therapy.

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6. Fig. 5. OS in patients with MM depending on the KRd therapy line.

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7. Fig. 6. PFS in patients with MM depending on the KRd therapy line.

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8. Fig. 7. PFS in patients with MM in KRd therapy (on the 2nd line), depending on the period from the date of diagnosis to the start of KRd therapy.

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