• Users Online: 128
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2020  |  Volume : 11  |  Issue : 2  |  Page : 74-76

The use of carfilzomib to treat extramedullary plasmacytoma and review of the literature

Department of Hematology, Baskent University School of Medicine, Istanbul, Turkey

Date of Submission05-Dec-2019
Date of Decision23-Feb-2020
Date of Acceptance21-Mar-2020
Date of Web Publication28-Jul-2020

Correspondence Address:
Dr. Figen Atalay
Oymac. Sk. No. 7 Altunizade, Uskudar, Istanbul
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joah.joah_83_19

Rights and Permissions

A 61-year-old woman was diagnosed with multiple myeloma (MM) (immunoglobulin G kappa type) in 2012. A bortezomib-based chemotherapy protocol was administered to the patient, and the patient underwent an autologous transplant. During lenalidomide maintenance therapy, she presented with anemia and extramedullary plasmacytomas (EMPs) with no bone marrow infiltration by clonal plasma cells. Her disease was in complete remission after six cycles of the carfilzomib-dexamethasone (KD) protocol. EMPs are seen in MM patients at the time of diagnosis or relapse. There is a challenge related to these patients' treatment schedules, as no consensus or standard treatment protocol has yet been defined. In this article, we present a case regarding the presentation of EMP relapse in a myeloma patient who is in remission after long-term carfilzomib therapy. We demonstrate that a KD treatment may be effective in patients with EMPs.

Keywords: Carfilzomib, maintenance, multiple myeloma, plasmacytoma

How to cite this article:
Atalay F. The use of carfilzomib to treat extramedullary plasmacytoma and review of the literature. J Appl Hematol 2020;11:74-6

How to cite this URL:
Atalay F. The use of carfilzomib to treat extramedullary plasmacytoma and review of the literature. J Appl Hematol [serial online] 2020 [cited 2023 Feb 4];11:74-6. Available from: https://www.jahjournal.org/text.asp?2020/11/2/74/290967

  Introduction Top

Multiple myeloma (MM) is a clonal plasma cell neoplasm that accounts for 13% of all hematological malignancies and for 1.8% of all cancers annually.[1] The International Myeloma Working Group (IMWG) revised the criteria for plasma cell disorders in 2014.[2] In this revision, plasmacytoma was defined as a solitary lesion of bone or soft tissue with clonal plasma cells, with no plasma cell infiltration in the bone marrow, no findings of skeletal involvement of the disease with imaging techniques (e.g., skeletal surveys, magnetic resonance imaging, or computerized tomography), and no evidence of any end-organ damage, including anemia, hypercalcemia, lytic bone lesions, and renal insufficiency. In the revision, MM was defined by the presence of ≥10% clonal plasma cell infiltration in bone marrow or bony or extramedullary plasmacytoma diagnosed by biopsy with findings of end-organ damage (renal insufficiency, hypercalcemia, anemia, and bone lesions).[2] In 2011, Bladé et al. described a subgroup of myeloma called extramedullary myeloma. In extramedullary myeloma, clonal plasma cell was detected in soft tissue or bone by biopsy.[3] Extramedullary plasmacytomas (EMPs) can be seen in MM patients at the time of diagnosis or relapse.[3] In 2010, Varettoni et al. published a large retrospective study and found that the percentage of EMPs at the time of diagnosis of MM and at relapse was 7% and 6%, respectively (difference from the incidence reported in the discussion part).[4] There is a challenge related to these patients' treatment schedules, as no consensus or standard treatment protocol has yet been defined.[5] In this article, we present a case report of the presentation of EMP relapse in a myeloma patient who is in remission after long-term carfilzomib therapy.

  Case Reports Top


A 61-year-old woman visited our hematology outpatient clinic in April 2012, presenting with weakness, dyspnea, weight loss, and palpitations. The physical examination revealed tachycardia, pale skin, and conjunctivitis. She had no prior medical history and did not take any medications. Her complaints started approximately 1 month before diagnosis. Her laboratory values were as follows: hemoglobin, 9.3 g/dl (12–16 g/dl); creatinine level, 1.78 mg/dl (0.5–1.3); erythrocyte sedimentation rate, 91 mm/h (0–20); total protein level, 9.4 g/dl (2.5–6); albumin, 3.9 g/dl (3.5–5.5); calcium level, 10.2 mg/dl (8.5–10.5); and immunoglobulin G (IgG kappa type) monoclonality in serum immunoelectrophoresis, β2 microglobulin level (0.97-2.64 mg/L). The pathological examination of the bone marrow biopsy revealed that the monoclonal kappa stained diffuse plasma cell infiltration. Multiple bone infiltration was seen in fluorodeoxyglucose (FDG) positron-emission tomography computed tomography (PET-CT). In light of these findings, the patient was diagnosed, according to the international scoring system,[6] with Stage-III MM (IgG kappa type), with normal karyotype and no additional cytogenetic abnormalities. A bortezomib -cyclophosphamide- dexamethasone protocol was administered weekly for four courses. The patient's anemia, renal functions, IgG, and kappa levels improved after four courses; no plasma cell infiltration was seen in the bone marrow, and she accepted as very good partial remission according to the IMWG response criteria.[7] The patient underwent an autologous transplant 4 weeks after finishing the induction therapy. A 10 mg lenalidomide maintenance therapy was administered following the autologous transplant. After 17 cycles of the lenalidomide treatment, the patient suddenly developed anemia (hemoglobin level, 8.9 g/dl). Simultaneously, palpable masses were detected on her cervical lesion. A bone marrow biopsy was repeated, and no plasma cell infiltration was detected. There was not any paraproteinemia and cytogenetic abnormality. The PET-CT revealed a 60 mm × 70 mm × 96 mm mass in the jugular area, an invasive left thyroid mass and diffuse bowel wall thickening at the pericecal area. All of the cervical and intestinal lesions were hypermetabolic (maximum standardized uptake values: 15.2 and 17.1, respectively). A tru-Cut biopsy was proven from the cervical lesion. There is an atypical plasma cell infiltration of nuclei with an eccentric location, perinuclear halo, some of which are binucleated. In these atypical cells, CD38 and kappa were monoclonally positive for immunohistochemistry. It is compatible with the EMP. The patient was diagnosed with EMP. and the plan was to give her a thalidomide-vincristine -doxorubicin-cisplatin-dexamethasone-etoposide (DT-PACE) chemotherapy protocol. After two cycles of the DT-PACE protocol, her PET-CT was compatible with minimal response, according to the IMWG criteria.[7] FDG uptake was still ongoing, especially the celiac area. Biopsy was taken from this area again, and it was compatible with plasmacytoma. The second autologous bone marrow transplantation could not be performed to the patient, since sufficient stem cells could not be stored during the first stem cell collection and that stem cell mobilization was not achieved despite plerixafor administration and the treatment response only in minimal according to the IMWG criteria.[7] It was decided to apply the carfilzomib-dexamethasone [KD] treatment protocol to the patient. Treatment was given as cardilzomib 20mg/m2/day in 1st cycle, 56mg/m2/day in subsequent cycles, intravenously on 1st, 2nd, 8th, 15th and 16th days, every 28 days. After six cycles of the KD protocol, the patient's hemoglobin level increased, and all of the hypermetabolic lesions disappeared from the PET-CT. According to the IMWG criteria, she was accepted as complete remission after six cycles. Overall, forty courses of the KD protocol were given to the patient, and she is in complete remission still and the patient did not have any cardiological morbidity depending on the treatment we applied.

  Discussion Top

Touzeau and Moreau wrote a comprehensive review of extramedullary myeloma disease in 2016. According to their article, in different studies on this topic different results have been found. The incidence of EMP is 6% -8% in de novo myeloma patients and 10% -30% in relapse/refractory patients. Patients who have elevated levels of lactate dehydrogenase (LDH), anemia, and thrombocytopenia have been shown to have very high risk of early progression and disease-related death.[5] Our patient relapsed during the use of lenalidomide maintenance therapy after an autologous bone marrow transplant, presenting with anemia, mild elevated serum levels of LDH (327, n = 225 U/L), and multiple EMPs. High LDH levels have been shown to be associated with poor prognosis, short survival, and extraosseous myeloma disease.[8] The relapsing mechanism of the EMP has not yet been fully defined. In 2007, Dawson et al. hypothesized that the use of lenalidomide and thalidomide could change the bone marrow microenvironment, and that after the use of these drugs, tumor cells may have the ability to spread beyond the bone marrow.[9] The upper respiratory system organs, the gastrointestinal system, the skin, and the endocrine glands can be affected by EMPs.[10] Our patient experienced thyroid gland and bowel infiltration by EMPs. At the same time, she presented with anemia, elevated LDH levels, and no bone marrow infiltration. She needed an urgent therapy for her disease. The DT-PACE protocol was administered to rapidly achieve the response. The DT-PACE protocol is an effective combination chemotherapy for high-risk patients such as our patient. In 2003, Lee et al. reported that high-risk and progressive patients can achieve 32% partial response and 16% complete and near-complete response with this protocol.[11] We were able to achieve only the minimal response with the DT-PACE protocol and needed to urgently change her therapy.

Carfilzomib is a second-generation proteasome inhibitor. The ENDEAVOR study is a phase-3 trial that used a combination of KD.[12] The ASPIRE study compared the carfilzomib-lenalidomide-dexamethasone (KRD) and lenalidomide-dexamethasone treatments.[13] In both studies, the results supported a prolongation of the life with the use of carfilzomib. Although recent guidelines advised that refractory patients be given triplet regimens (NCCN), we had used the KD combination because our patient was already refractory to the lenalidomide. Carfilzomib is an effective therapy for EMPs such as MM. In 2017, Español et al. reported that a KD chemotherapy protocol was effective for a patient with pleural and pericardial involvement.[14] In another case report that a KRD protocol used without radiotherapy in a patient with brain involvement responded well, the authors commented that the use of the karfilzomib and lenalidomide together could be effective in plasmacytomas.[15] In our patient, we achieved a complete response to a KD treatment in 6 months. MM is still not fully cured, despite many newly emerging agents. Maintenance therapy after transplantation prolongs disease-free survival and possibly overall survival, as well as for maintaining deep response and achieved response.[16]

Our patient has been receiving carfilzomib maintenance therapy for 40 months, and to our knowledge, there are no patients in the literature who have been in remission for so long.

A KD treatment may, therefore, be effective in patients with EMP. In addition, if applying this treatment can keep the disease under control, then it is appropriate to continue the current treatment; so long as there are no side effects related to the treatment, the disease can be kept under control.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol 2016;43:676-81.  Back to cited text no. 1
Rajkumar V, Dimopoulos MA, Palumbo A, Blade J, Merlini G. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:538-48.  Back to cited text no. 2
Bladé J, Fernández de Larrea C, Rosiñol L, Cibeira MT, Jiménez R, Powles R. Soft-tissue plasmacytomas in multiple myeloma: Incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol 2011;29:3805-12.  Back to cited text no. 3
Varettoni M, Corso A, Pica G, Mangiacavalli S, Pascutto C, Lazzarino M. Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: A longitudinal study on 1003 consecutive patients. Ann Oncol 2010;21:325-30.  Back to cited text no. 4
Touzeau C, Moreau P. How I treat extramedullary myeloma. Blood 2016;127:971-6.  Back to cited text no. 5
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. JCO 2005;23:3412-20.  Back to cited text no. 6
Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17:e328-46.  Back to cited text no. 7
Barlogie B, Smallwood L, Smith T, Alexanian R. High serum levels of lactic dehydrogenase identify a high-grade lymphoma-like myeloma. Ann Intern Med 1989;110:521-5.  Back to cited text no. 8
Dawson MA, Patil S, Spencer A. Extramedullary relapse of multiple myeloma associated with a shift in secretion from intact immunoglobulin to light chains. Haematologica 2007;92:143-4.  Back to cited text no. 9
Sun WJ, Zhang JJ, An N, Shen M, Huang ZX, Li X. Clinical analysis of 40 multiple myeloma patients with extramedullary plasmacytoma of the head. J Int Med Res 2016;44:1462-73.  Back to cited text no. 10
Lee CK, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J, et al. DTPACE: An effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol 2003;21:2732-9.  Back to cited text no. 11
Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): A randomised, phase 3, open-label, multicentre study. Lancet Oncol 2016;17:27-38.  Back to cited text no. 12
Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015;372:142-52.  Back to cited text no. 13
Español I, Romera M, Gutiérrez-Meca MD, García MD, Tejedor A, Martínez A, et al. Carfilzomib and dexamethasone for extramedullary myeloma with pleuropericardial involvement. Clin Case Rep 2017;5:1258-60.  Back to cited text no. 14
Mele G, Pastore D. Efficacy of carfilzomib, lenalidomide, and dexamethasone for extramedullary intracranial localization of multiple myeloma. Case Rep Hematol 2018;2018:2312430.  Back to cited text no. 15
Mewawalla P, Chilkulwar A. Maintenance therapy in multiple myeloma. Ther Adv Hematol 2017;8:71-9.  Back to cited text no. 16

This article has been cited by
1 Identification of patients at high risk of secondary extramedullary multiple myeloma development
Martin Stork, Sabina Sevcikova, Jiri Minarik, Petra Krhovska, Jakub Radocha, Lenka Pospisilova, Lucie Brozova, Jiri Jarkovsky, Ivan Spicka, Jan Straub, Petr Pavlicek, Alexandra Jungova, Tomas Jelinek, Viera Sandecka, Vladimir Maisnar, Roman Hajek, Ludek Pour
British Journal of Haematology. 2021; 1833(1): 231
[Pubmed] | [DOI]
2 Lenalidomide/plerixafor
Reactions Weekly. 2020; 1833(1): 231
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case Reports

 Article Access Statistics
    PDF Downloaded166    
    Comments [Add]    
    Cited by others 2    

Recommend this journal