List of Abbreviations
BM – bone marrow
BP – bone plasmacytoma
CT – computed tomography
LDH – lactate dehydrogenase
RT – radiotherapy
ICD-10 – International Classification of Diseases 10th Revision
MM – multiple myeloma
MRI – magnetic resonance imaging
PET/CT – whole-body positron emission tomography combined with computed tomography
FLC – free light chains
SP – solitary plasmacytoma
EP – extramedullary plasmacytoma
CRAB – syndrome: a constellation of organ damage in symptomatic multiple myeloma: hypercalcemia, renal dysfunction, anemia, bone lesions
ECOG – Eastern Cooperative Oncology Group
IMWG – International Myeloma Working Group
RECIST – Response Evaluation Criteria in Solid Tumors
** – vital and essential drugs
# – drug used off-label (not in accordance with the indications, contraindications, routes of administration, or dosages specified in the drug's package insert)
Terms and Definitions
Multiple myeloma is a B-cell malignant tumor whose morphological substrate consists of plasma cells producing a monoclonal immunoglobulin. According to the latest 2017 World Health Organization (WHO) classification, the term "multiple myeloma" was replaced by "plasma cell myeloma," defined as a disease characterized by the multifocal proliferation of neoplastic plasma cells associated with the secretion of a monoclonal immunoglobulin.
Solitary plasmacytoma (SP) is a rare form of plasma cell tumor characterized by local proliferation of clonal plasma cells without other lesions in bones and soft tissues, while there are no signs of organ and systemic damage associated with plasma cell proliferation.
Progression-free survival is the time from the date treatment starts to disease progression or patient death from any cause.
Monoclonal immunoglobulin – an immunoglobulin of a single class synthesized in excess by a clonal plasma cell. The immunoglobulin structure remains normal, but the synthesis of the immunoglobulin or its individual components exceeds physiological requirements.
M-protein spike – a narrow, distinct band on an electrophoretogram formed by monoclonal immunoglobulins.
Overall survival is the time from the date treatment starts to patient death from any cause or the date of the patient's last follow-up visit.
Plasma cell is the final stage of B-lymphocyte differentiation. Its functional activity includes participation in humoral immunity and antibody production.
Remission is a period of the disease course characterized by significant abatement or complete disappearance of symptoms, including data from performed laboratory and instrumental diagnostic methods.
Relapse – the return of clinical manifestations of the disease, including based on laboratory and instrumental diagnostic methods.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Solitary plasmacytoma (SP) is a rare form of plasma cell tumor characterized by local proliferation of clonal plasma cells without other lesions in bones and soft tissues, while there are no signs of organ and systemic damage associated with plasma cell proliferation.
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The etiology is unknown; in pathogenesis, a definite role is assigned to prolonged, chronic antigenic stimulation resulting from viral infections or other chronic diseases, long-term exposure to toxic substances and radiation. As a result of a series of genetic events, a pathological clone of B cells is formed that is capable of differentiating into plasma cells but produces a non-functional immunoglobulin [1–3].
1.3 Epidemiology of the Disease or Condition
Solitary plasmacytoma is a rare disease, with an incidence rate of < 5% of plasma cell tumors. SP is more commonly observed in men. Patients tend to be younger than those with multiple myeloma (MM), with a median age of onset of 55 years. Solitary bone plasmacytoma accounts for 70% of all SP cases, with frequent localizations being the vertebrae, femurs, pelvis, and ribs. Extramedullary plasmacytoma can affect any organ, most commonly the head and neck region (sinuses, nasopharynx, oropharynx), gastrointestinal tract, and lungs [4–6].
1.4 Features of Coding the Disease or Condition
C90.2 – Extramedullary plasmacytoma
C90.3 – Solitary plasmacytoma
1.5 Classification of the disease or condition
According to the World Health Organization classification, depending on the location of the lesion, bone plasmacytoma (BP) and extramedullary plasmacytoma (EP) are distinguished [7].
Solitary BP is diagnosed upon the detection of a single lytic bone lesion with an intraosseous tumor, or with involvement of adjacent organs and tissues upon destruction of the cortical bone layer. Solitary EP can arise in any organs and tissues outside of bone structures.
In accordance with the criteria of the International Myeloma Working Group (IMWG) (2014), two variants of SP are distinguished: SP without bone marrow involvement and SP with minimal bone marrow involvement (up to 10% clonal plasma cells) [8].
SP patients with minimal bone marrow involvement are in the high-risk group for developing symptomatic MM. According to the results of two independent studies, progression to MM was observed in 71–72% of SP patients with minimal bone marrow involvement versus 8–12.5% of SP patients without bone marrow involvement [9, 10].
1.6 Clinical presentation of the disease or condition
The clinical manifestations of SP are extremely diverse and are determined by the location and extent of the tumor process. Bone pain is the most frequent symptom in BP. Other manifestations of BP may include spinal cord and nerve root compression, pathological fracture, and a palpable mass. In half of the cases, solitary BP progresses to MM within 3–4 years. Progression of solitary EP to MM is rarely described [6].
2. Diagnostics, medical indications and contraindications for diagnostic methods
Many recommended diagnostic methods for the disease and associated conditions have a limited evidence base (according to the grading scales for reliability of evidence and clinical practice guideline recommendation strength) due to the lack of clinical studies dedicated to them. Despite this, they are necessary elements of patient evaluation for establishing a diagnosis and selecting treatment tactics, since more effective and proven methods have not yet been developed.
Criteria for establishing the diagnosis/condition:
presence of a single bone or soft tissue lesion represented by clonal plasma cells, confirmed by histological and immunohistochemical studies, without bone marrow involvement or with minimal signs of involvement (<10% clonal plasma cells in the bone marrow);
absence of signs of the CRAB syndrome (see MM treatment guidelines);
Comment: upon immunochemical analysis of serum and urine proteins, a monoclonal protein can be detected in the blood in 24–72% of SP cases; Bence Jones protein excretion is less common. An abnormal serum free light chain (FLC) ratio is associated with a higher risk of progression to MM [11]
2.1 Complaints and Anamnesis
For all patients with suspected SP, as well as all patients with verified SP at each visit, it is recommended to take an anamnesis and record complaints related to blood and hematopoietic organ diseases to assess the patient's condition [6, 12].
Strength of recommendation – C (level of evidence reliability – 5).
2.2 Physical Examination
For all patients with suspected or confirmed SP at the initial or follow-up visit, during check-ups, and when disease relapse is suspected, it is recommended to perform a physical examination (general inspection, palpation, and auscultation) and assess the general condition using the Eastern Cooperative Oncology Group (ECOG) scale [6, 12, 13, 14].
Strength of recommendation – C (level of evidence reliability – 5).
Comment: during the examination, it is necessary to assess the patient's general condition using the ECOG scale (Appendix G1), as well as inspect the tonsils and oral cavity; palpation should include accessible peripheral lymph node groups, the liver, and the spleen.
2.3 Laboratory Diagnostics
For all patients with suspected or confirmed SP at initial or follow-up visits, during follow-up examinations, and when relapse / progression to MM is suspected, to clarify the patient's general condition, determine the feasibility of treatment and/or (in case of prior therapy) the development of adverse treatment events, it is recommended to perform the following clinical tests [6, 12, 14]:
complete blood count (CBC) with differential, including assessment of total hemoglobin, erythrocytes, platelets, and leukocytes, and white blood cell differential (leukocyte formula);
general (clinical) urinalysis;
general clinical blood chemistry panel (including blood lactate dehydrogenase (LDH) activity, creatinine, total protein, albumin, and ionized calcium levels).
GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).
For all patients with suspected SP, it is recommended to perform a biopsy of tumors and soft-tissue tumor-like formations followed by intravital pathoanatomical examination of the biopsy (surgical) material using immunohistochemical methods for morphological verification of the diagnosis [6].
GOM CLOE 4Level of Evidence – C (Level of Data Reliability – 4).
Comment: the diagnosis of SP is established based on the detection of monoclonal plasma cell infiltration in the lesion site. Performing an immunohistochemical study of the biopsy material is mandatory.
For all patients with suspected or confirmed SP at the initial visit, or when relapse / progression to MM is suspected, it is recommended to obtain a bone marrow cytologic preparation via aspiration and perform immunophenotyping of the biological material to identify markers of hemoblastoses [1, 14].
GCR CLOE 5Grade of Recommendations – C (Level of Evidence – 5).
Comment: If it is not possible to perform an immunophenotypic study by flow cytometry, an immunohistochemical study of a bone marrow trephine biopsy can be performed to detect a monoclonal plasma cell population (pathoanatomical examination of bone marrow biopsy [surgical] material using immunohistochemical methods)
For all patients with suspected SP, it is recommended to obtain a bone marrow histological preparation (trephine biopsy) and perform a pathoanatomical examination of the bone marrow biopsy (surgical) material [1, 14].
GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).
In all patients with suspected or confirmed SP at initial or follow-up visits, during follow-up examinations, and in cases of suspected relapse/progression in MM, it is recommended to determine the protein fraction ratio by electrophoresis, test for immunoglobulin monoclonality in blood by immunofixation, determine the levels of serum free kappa and lambda light chains, test for immunoglobulin monoclonality in urine by immunofixation, and assay serum immunoglobulins with quantification of monoclonal and polyclonal immunoglobulins [1, 6, 11, 14].
GPP CLoE 5Grade of Recommendation – C (Level of Evidence – 5).
In all patients with suspected or confirmed SP at the initial visit and when relapse/progression in MM is suspected, it is recommended to test the serum beta-2-microglobulin level for staging according to the current classification [6, 14].
GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).
In all patients with suspected or diagnosed SP at the initial visit, it is recommended to test for hepatitis B virus surface antigen (HbsAg) in the blood and antibodies class G (anti-HCV IgG) to hepatitis C virus (Hepatitis C virus) in the blood to determine the need for therapy or prevention of viral hepatitis reactivation [16].
Grade of Recommendation − C (Level of Evidence − 5).
In all patients with suspected or diagnosed SP at the initial visit, it is recommended to test for IgM and IgG antibodies to human immunodeficiency virus type 2 (HIV-2) in the blood and human immunodeficiency virus type 1 (HIV-1) p24 antigen in the blood to determine the need for concurrent anti-tumor and antiretroviral therapy [16].
Grade of Recommendation − C (Level of Evidence − 5).
2.4 Instrumental Diagnostics
In all patients with SP at the time of diagnosis, to determine the presence and extent of bone lesions and measure the plasmacytoma size, it is recommended to perform computed tomography of the facial skull, spine (one segment), chest organs, and pelvic bones (low-dose whole-body CT is preferred) [1].
GCR CLOE 5 Grade of Recommendations — C (Level of Evidence — 5).
In patients with SP with no osteodestructive process on CT, to detect bone marrow lesions and determine the localization and size of the plasmacytoma, as well as in suspected spinal cord compression, it is recommended to perform magnetic resonance imaging of the spine (one segment) (MRI of all spinal segments and the pelvis must be performed) [1].
GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).
In patients with SP with no osteodestructive process on CT and no abnormal bone marrow signal foci on MRI, to rule out additional hypermetabolic foci, it is recommended for SP patients to undergo PET/CT (positron emission tomography combined with whole-body computed tomography) [1].
LeR CLoE 5Level of Recommendation C (Level of Evidence — 5)
Comments: It is advisable to perform MRI of all spinal segments and the pelvis. According to a number of experts, MRI and PET/CT are necessary to rule out additional lesions; the use of at least one of these methods is mandatory.
2.5 Other Procedures
Absent
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1. Radiotherapy
In all patients with diagnosed SP, it is recommended to administer external beam radiotherapy (RT). The total fractionated dose should be 40–50 Gy, and the radiation field should extend at least 2 cm beyond the tumor margins [6, 17, 18].
Level of Evidence CGrade of Recommendation 4Level of Evidence – C (Grade of Recommendation – 4).
Comment: local control rates of 80–90% can be achieved only with RT at a dose of >40 Gy. In clinical practice, higher doses close to 50 Gy are usually applied, especially for tumor volumes >5 cm. When planning treatment, MRI is the most accurate imaging modality, but CT can also be used. If there is any uncertainty regarding the boundaries of bone involvement, the entire bone may be included in the radiation field. For spinal lesions, 1 vertebra above and 1 vertebra below the affected area are included in the radiation field [6]. If the patient has undergone surgical treatment using fixation devices, any implanted fixation device is included in the radiation field. With external beam RT, inclusion of regional lymph nodes is usually not required. However, irradiation of regional lymph nodes may be considered in the treatment of SP when dealing with high-risk regions, such as the head, neck, and Waldeyer's ring [19]. For plasmacytomas <5 cm in size, a dose of 40 Gy with fractionation at 1.8–2 Gy once daily is recommended. For plasmacytomas >5 cm, a dose of 40 to 50 Gy is recommended.
3.2. Surgical treatment
In patients with solitary bone plasmacytoma, surgical intervention is recommended for the treatment of pathological fractures, lesions with a high probability of fracture requiring fixation, and neurological complications [1, 20].
GOM CLOE 4Level of Evidence – C (Level of Data Reliability – 4).
Comments: in patients with extramedullary plasmacytoma, surgery may allow the removal of large, well-defined masses. Postoperative RT is mandatory, as tumor removal without subsequent radiation therapy leads to a high rate of local recurrence.
3.3. Systemic antineoplastic therapy
The role of adjuvant chemotherapy after RT in the management of solitary plasmacytoma remains controversial, precluding a definitive recommendation.
The experts (authors) of these guidelines, based on their own clinical experience and literature data, concluded that combined treatment (systemic anti-tumor therapy and local radiotherapy) is advisable for a specific group of SP patients with high risk factors for transformation into symptomatic MM. These factors include minimal bone marrow infiltration by aberrant plasma cells, additional hypermetabolic foci on PET/CT, plasmacytoma size > 5 cm, abnormal FLC ratio (>50), persistence of paraprotein after RT, and lack of a deep anti-tumor response after RT.
In patients with SP who are candidates for systemic chemotherapy, it is recommended to choose a systemic chemotherapy regimen in accordance with national clinical guidelines for the diagnosis and treatment of symptomatic MM, based on age, patient performance status, and comorbidity [1].
GCR CLOE 5Grade of Recommendations – C (Level of Evidence – 5).
In patients with SP with confirmed osteoporosis, it is recommended to use bisphosphonates at doses used for patients with osteoporosis. Systemic use of bisphosphonates is possible for patients with solitary bone plasmacytoma in the presence of massive destruction or fracture risk [1].
GCR CLOE 5Grade of Recommendations – C (Level of Evidence – 5).
Comments: in the study by Holland et al., adjuvant chemotherapy did not affect the progression rate to MM, but delayed progression from 29 to 59 months [21]. It is worth noting that the study was conducted prior to the advent of targeted therapies and included 46 patients, of whom only 14 received chemotherapy following RT. According to a retrospective study by French authors comparing treatment outcomes in a group of SP patients who received chemotherapy combined with radiotherapy (n=20) and a group of patients who received radiotherapy alone (n=32), no differences were found when evaluating 5-year PFS and OS (patients received various treatment regimens including melphalan**, bortezomib**, glucocorticoids) [22]. In another French study, 27 SP patients received RT alone, while 19 patients underwent RT combined with 4 cycles of Rd (lenalidomide**+dexamethasone**). PFS was significantly higher in the RT combined with Rd group compared to the group of patients who received RT alone (81.7% vs. 48.4%, p= .047), with no differences observed in OS rates [23]. Studies have shown that persistence of the M-spike following RT is a poor prognostic factor. Thus, according to Wilder et al., the 10-year progression-free survival to MM was 91% for solitary bone plasmacytoma patients who achieved immunochemical remission after RT, compared to 29% for patients who maintained an M-spike for more than a year post-RT [24]
4. Medical Rehabilitation and Sanatorium-Resort Treatment
There are no special rehabilitation methods for SP.
In all patients with SP at all stages of the disease, as well as after completion of medical treatment, comprehensive rehabilitation is recommended [26].
GCR CLOE 5Grade of Recommendations – C (Level of Evidence – 5).
Comments: rehabilitation of patients with SP must be comprehensive, covering the medical, social, and psychological aspects of the patient's adaptation to normal life. The scope of medical rehabilitation is developed individually for each patient by a physical therapy physician in cooperation with a hematologist, depending on the disease course, manifestations, and interventions performed. In addition, the rehabilitation program must take into account the patient's social and psychological problems and requires, alongside medical care, the mandatory involvement of social workers and psychologists. Rehabilitation for complications arising during the course of the disease and treatment is carried out within the framework of the corresponding nosologies.
5. Prevention and Dispensary Observation
All patients with SP throughout their life—both during and outside of SP treatment—are recommended routine dispensary appointments (examination, consultation) with a hematologist/oncologist [14].
GCR CLOE 5Grade of Recommendations – C (Level of Evidence – 5).
Comments: dispensary follow-up must include laboratory and instrumental diagnostic methods. Laboratory diagnostics are performed upon completion of the radiotherapy stage and then every 3 months for the first 2 years after radiotherapy, and every 6 months thereafter; diagnostic imaging is performed 3 months after completion of the radiotherapy stage, and subsequently as clinically indicated.
Laboratory diagnostics within the framework of dispensary follow-up should include a complete blood count; general therapeutic biochemical blood analysis (determination of blood lactate dehydrogenase (LDH) activity, testing of creatinine, total protein, albumin, and ionized calcium levels in the blood); determination of protein fraction ratios by electrophoresis, investigation of immunoglobulin monoclonality in the blood by immunofixation, determination of free kappa and lambda light chain levels in the blood, investigation of immunoglobulin monoclonality in the urine by immunofixation, and testing of blood immunoglobulin levels with quantification of monoclonal and polyclonal immunoglobulins. The persistence of serum monoclonal protein after radiotherapy is a high-risk factor for transformation to MM, indicating the need for monitoring of blood and urine protein electrophoresis and immunofixation.
For dynamic monitoring, the same imaging method (Section 2.4) as at disease onset should be used; it should be remembered that PET/CT has a higher sensitivity than MRI.
Response to treatment should be assessed in accordance with IMWG criteria for patients with measurable parameters of pathological secretion. For soft tissue lesions, these criteria should be combined with the RECIST (Response Evaluation Criteria in Solid Tumors) criteria — Appendix A3, Table 5.
6. Organization of Medical Care
Medical care, with the exception of medical care provided as part of clinical trials, in accordance with Federal Law No. 323-FZ dated November 21, 2011 (as amended on May 25, 2019) "On the Fundamentals of Protecting Public Health in the Russian Federation", is organized and provided:
in accordance with the regulations on the organization of the provision of medical care by types of medical care, which is approved by the authorized federal executive body;
in accordance with the procedure for the provision of care for the profile "hematology", mandatory for execution on the territory of the Russian Federation by all medical organizations;
based on these clinical guidelines;
taking into account the standards of medical care approved by the authorized federal executive body.
Primary specialized health care is provided by a hematologist and other medical specialists at an ambulatory hematology/oncology care center, a primary hematology/oncology office, a primary hematology department, or an outpatient department of an oncological dispensary.
If SP is detected or suspected in a patient, general practitioners, district general practitioners, general family physicians, specialist physicians, and mid-level medical personnel shall refer the patient in the established manner for consultation to an ambulatory hematology/oncology center or a primary hematology office, or a primary hematology department of a medical organization for primary specialized health care.
An outpatient or inpatient hematologist organizes the diagnostic tests necessary to establish the diagnosis, including disease extent and stage.
If diagnostic tests cannot be performed, the attending physician refers the patient to a medical organization providing medical care to patients with hematological diseases to establish a diagnosis and provide specialized, including high-tech, medical care.
If SP is detected or suspected during the provision of emergency medical care, the patient is transferred or referred to medical organizations providing medical care to patients with hematological diseases to determine management tactics and the need for additional specialized anti-tumor treatment methods.
Specialized, including high-tech, medical care is provided by hematologists and oncologists in medical organizations providing care to patients with SP that hold a license, have the necessary material and technical base, and employ certified specialists, in inpatient and day-hospital settings, and includes the prevention, diagnosis, and treatment of hematological diseases requiring special methods and complex unique medical technologies, as well as medical rehabilitation.
In a medical organization providing medical care to patients with SP, the tactics of medical examination and treatment are established by hematologists/oncologists with the involvement of other medical specialists if necessary, and with a medical board (consilium) convened when required. The decision of the medical board is formalized in a protocol, signed by the participating physicians, and entered into the patient's medical documentation.
Indications for hospitalization in a 24-hour or day hospital of a medical organization providing specialized, including high-tech, medical care in the specialty "hematology" are determined by a hematologist/medical panel with the involvement of other medical specialists if necessary.
Indication for planned hospitalization in a medical organization:
presence of an SP diagnosis to perform local radiotherapy / systemic anti-tumor therapy.
Indications for emergency hospitalization to a medical organization:
severe bone pain syndrome (including risk of fractures, spinal damage, spinal cord compression);
severe complications associated with specific therapy.
Indications for patient discharge from a medical organization
completion of a course of local radiotherapy, systemic anti-tumor therapy;
resolution of complications arising from specific therapy.
The conclusion on the advisability of transferring a patient to a specialized medical organization is made after a preliminary consultation on the provided medical documents and/or a preliminary examination of the patient by specialist physicians of the medical organization to which the transfer is planned.
7. Additional Information
No additional information available
Criteria for Evaluating the Quality of Medical Care
Table 1. Criteria for assessing the quality of medical care
No. | Quality criterion | Performance evaluation |
|---|---|---|
1 | A patient with suspected SP underwent pathomorphological examination of biopsy (surgical) material using immunohistochemical methods | Yes/No |
2 | A patient with suspected SP or diagnosed SP during follow-up examinations and suspected relapse or progression to MM underwent a complete blood count including hemoglobin, erythrocyte, platelet, and leukocyte levels, with a differential white blood cell count | Yes/No |
3 | A patient with suspected SP or diagnosed SP during follow-up examinations and suspected relapse or progression to MM underwent a general therapeutic biochemical blood analysis (with determination of blood lactate dehydrogenase activity, testing of creatinine, total protein, albumin, and ionized calcium levels in the blood) | Yes/No |
4 | A patient with suspected SP or diagnosed SP during follow-up examinations and suspected relapse or progression to MM underwent a urinalysis | Yes/No |
5 | A patient with suspected SP or diagnosed SP during follow-up examinations and suspected relapse or progression to MM underwent determination of protein fraction ratios by electrophoresis, investigation of immunoglobulin monoclonality in the blood by immunofixation, determination of free kappa and lambda light chain levels in the blood, investigation of immunoglobulin monoclonality in the urine by immunofixation, and testing of blood immunoglobulin levels with quantification of monoclonal and polyclonal immunoglobulins. | Yes/No |
6 | A patient with suspected SP or diagnosed SP at the initial visit, or with suspected relapse / progression to MM, underwent bone marrow cytology preparation via aspiration | Yes/No |
7 | A patient diagnosed with SP, or with suspected disease relapse or progression to MM, underwent computed tomography of the facial skull and spine (one segment) (low-dose whole-body CT is preferred) or magnetic resonance imaging of the spine (one segment) (whole-body MRI is preferred), or PET/CT, to determine the presence and extent of bone lesions and identify plasmacytomas with measurement of their dimensions | Yes/No |
References
Show references
Caers J, Paiva B, Zamagni E, et al. Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel. J Hematol Oncol. 2018;11(1). doi:10.1186/S13045-017-0549-1
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548. doi:10.1016/S1470-2045(14)70442-5
Kuehl WM, Bergsagel PL. Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest. 2012;122(10):3456-3463. doi:10.1172/JCI61188
M Hallek, P L Bergsagel, K C Anderson Multiple myeloma: increasing evidence for a multistep transformation process - Blood 1998 Jan 1;91(1):3-21.
Furukawa Y, Kikuchi J. Molecular pathogenesis of multiple myeloma. Int J Clin Oncol. 2015;20(3):413-422. doi:10.1007/S10147-015-0837-0
Ozsahin M, Tsang RW, Poortmans P, et al. Outcomes and patterns of failure in solitary plasmacytoma: a multicenter Rare Cancer Network study of 258 patients. Int J Radiat Oncol Biol Phys. 2006;64(1):210-217. doi:10.1016/J.IJROBP.2005.06.039
Liebross RH, Ha CS, Cox JD, et al. Clinical course of solitary extramedullary plasmacytoma. Radiother Oncol. 1999;52(3):245-249. doi:10.1016/S0167-8140(99)00114-0
Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.; 2017.
Hill QA, Rawstron AC, De Tute RM, et al. Outcome prediction in plasmacytoma of bone: a risk model utilizing bone marrow flow cytometry and light-chain analysis. Blood. 2014;124(8):1296-1299. doi:10.1182/BLOOD-2014-04-566521
Paiva B, Chandia M, Vidriales MB, et al. Multiparameter flow cytometry for staging of solitary bone plasmacytoma: new criteria for risk of progression to myeloma. Blood. 2014;124(8):1300-1303. doi:10.1182/BLOOD-2014-04-567909
Dispenzieri A, Kyle R, Merlini G, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009;23(2):215-224. doi:10.1038/LEU.2008.307
Grammatico S, Scalzulli E, Petrucci MT. Solitary Plasmacytoma. Mediterr J Hematol Infect Dis. 2017;9(1). doi:10.4084/MJHID.2017.052
Guo SQ, Zhang L, Wang YF, et al. Prognostic factors associated with solitary plasmacytoma. Onco Targets Ther. 2013;6:1659-1666. doi:10.2147/OTT.S53248
Mendeleeva L.P., Votyakova O.M. Solitary Plasmacytoma // Russian Clinical Guidelines for the Diagnosis and Treatment of Malignant Lymphoproliferative Diseases; Ed. by I.V. Poddubnaya, V.G. Savchenko.; 2018.
Chang WI, Koh HK, Yoon SS, et al. The predictive value of serum myeloma protein in solitary plasmacytoma. Radiat Oncol J. 2020;38(2):129-137. doi:10.3857/ROJ.2019.00570
Mendeleeva L.P., Votyakova O.M. Multiple Myeloma // Russian Clinical Guidelines for the Diagnosis and Treatment of Malignant Lymphoproliferative Diseases; Ed. by I.V. Poddubnaya, V.G. Savchenko. Moscow; 2018.
Mendenhall WM, Mendenhall CM, Mendenhall NP. Solitary plasmacytoma of bone and soft tissues. Am J Otolaryngol. 2003;24(6):395-399. doi:10.1016/S0196-0709(03)00092-9
Tsang RW, Gospodarowicz MK, Pintilie M, et al. Solitary plasmacytoma treated with radiotherapy: impact of tumor size on outcome. Int J Radiat Oncol Biol Phys. 2001;50(1):113-120. doi:10.1016/S0360-3016(00)01572-8
Tsang RW, Campbell BA, Goda JS, et al. Radiation Therapy for Solitary Plasmacytoma and Multiple Myeloma: Guidelines From the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2018;101(4):794-808. doi:10.1016/J.IJROBP.2018.05.009
Knobel D, Zhouhair A, Tsang RW, et al. Prognostic factors in solitary plasmacytoma of the bone: a multicenter Rare Cancer Network study. BMC Cancer. 2006;6. doi:10.1186/1471-2407-6-118
Holland J, Trenkner D A, Wasserman T H et al. Plasmacytoma. Treatment results and conversion to myeloma - PubMed. Cancer. 1992;69(6):1513-1517. https://pubmed.ncbi.nlm.nih.gov/1540888/. Accessed January 27, 2022.
Kayane Mheidly, Thierry Lamy, Martine Escoffre, et al. Adjuvant chemotherapy in the treatment of solitary bone plasmacytoma. 2016.
Mignot F, Schernberg A, Arsène-Henry A, et al. Solitary Plasmacytoma Treated by Lenalidomide-Dexamethasone in Combination with Radiation Therapy: Clinical Outcomes. Int J Radiat Oncol Biol Phys. 2020;106(3):589-596. doi:10.1016/J.IJROBP.2019.10.043
Wilder RB, Ha CS, Cox JD, et al. Persistence of myeloma protein for more than one year after radiotherapy is an adverse prognostic factor in solitary plasmacytoma of bone. Cancer. 2002;94(5):1532-1537. http://www.ncbi.nlm.nih.gov/pubmed/11920511. Accessed May 18, 2017.
M M Oken, R H Creech, D C Tormey, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. doi:10.1097/00000421-198212000-00014
Paul K.L. Rehabilitation and exercise considerations in hematologic malignancies. // Am.J. Phys. Med. Rehabil. 2011. Vol. 90, № 5 Suppl 1. P. S88-94.
Appendix A1. Working Group Composition
Larisa P. Mendeleeva – D.Sc. (Medicine), Professor, Head of the Department for Scientific and Educational Work at the National Research Center for Hematology of the Russian Ministry of Health, Head of the Department of Chemotherapy of Paraproteinemic Hemoblastoses, Member of the Supervisory Board of the Association for the Promotion of Hematology, Transfusion, and Bone Marrow Transplantation "National Hematological Society"
Elena N. Parovichnikova – D.Sc. (Medicine), General Director of the National Research Center for Hematology of the Russian Ministry of Health, Chairperson of the Association for the Promotion of Hematology, Transfusion, and Bone Marrow Transplantation "National Hematological Society"
Maya V. Solovyova – MD, PhD, Senior Researcher at the Department of Chemotherapy for Paraproteinemic Hemoblastosis, National Medical Research Center for Hematology of the Russian Ministry of Health, Member of the Association for the Promotion of Hematology, Transfusion and Bone Marrow Transplantation "National Hematological Society".
Maxim V. Solovyev – Ph.D. (Medicine), Head of the Department of Hematology and High-Dose Chemotherapy of Paraproteinemic Hemoblastoses with BMT and HSC Unit at the National Research Center for Hematology of the Russian Ministry of Health, Member of the Association for the Promotion of Hematology, Transfusion, and Bone Marrow Transplantation "National Hematological Society"
Natalia A. Falaleeva – D.Sc. (Medicine), Head of the Department of Antitumor Drug Treatment at the Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Russian Ministry of Health, Member of the Russian Society of Clinical Oncology and the Russian Association of Therapeutic Radiation Oncologists.
Irina V. Poddubnaya – Academician of the RAS, Honored Worker of Education of the RF, D.Sc. in Medicine, Professor, Head of the Department of Oncology and Palliative Medicine, Vice-Rector for Clinical Work and International Cooperation at the Russian Medical Academy of Continuous Professional Education (RMANPO) of the Russian Ministry of Health, Chairman of the Russian Society of Oncohematologists.
Alena Yu. Terekhova – Ph.D. in Medicine, Head of the Department of Radiation and Drug Treatment of Hemoblastoses at the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Russian Ministry of Health, member of the Association of Oncologists of Russia and the Russian Association of Therapeutic Radiation Oncologists.
Evgeny A. Osmanov – D.Sc. in Medicine, Professor, Head of the Department of Hematology and Bone Marrow Transplantation at the N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, Professor at the Department of Oncology of the I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Russian Ministry of Health, member of the Association for the Promotion of Hematology, Transfusiology and Bone Marrow Transplantation "National Hematology Society".
There is no conflict of interest.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
hematologists;
oncologists;
medical students.
Methods used to collect/select evidence: search for publications in peer-reviewed periodicals with an impact factor >0.3; search in electronic databases.
Databases used to collect/select evidence. The evidence base for the recommendations includes publications indexed in the Cochrane Library, PubMed, and MedLine databases. The search depth was 30 years.
Methods used for evidence analysis:
reviews of published meta-analyses;
systematic reviews with evidence tables.
Methods used for assessing the quality and strength of evidence:
expert consensus;
evaluation of the significance of evidence in accordance with the evidence rating scheme (Tables 2‒4).
These clinical guidelines present the levels of evidence for recommendations in accordance with the draft methodological guidelines for assessing the validity of evidence and the persuasiveness of recommendations from the Center for Expertise and Quality of Medical Care of the Russian Ministry of Health.
In accordance with this draft of recommendations, certain generally accepted diagnostic methods have been assigned a GPP (Good Clinical Practice) level based on expert consensus.
Table 2. Scale for assessing the levels of certainty of evidence for diagnostic methods (diagnostic interventions)
Level of evidence | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized clinical trials with meta-analysis |
2 | Individual studies with reference-method control, or individual randomized controlled trials and systematic reviews of studies of any design except randomized controlled trials incorporating meta-analysis |
3 | Studies without sequential reference-standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 3. Scale for assessing levels of evidence (LoE) for methods of prevention, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)
Level of evidence | Definition |
|---|---|
1 | Systematic review of randomized controlled trials with meta-analysis |
2 | Individual randomized clinical trials and systematic reviews of studies of any design, excluding randomized clinical trials with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 4. Scale for assessing the levels of recommendation grades (LRG) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on the use of natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitation interventions)
Grade of Recommendation | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies have low methodological quality, and their conclusions on the outcomes of interest are inconsistent)) |
Methods of validation of recommendations:
external expert review;
internal expert review.
Procedure for updating clinical guidelines. The updating of clinical guidelines is carried out at least once every 2 years or earlier, taking into account new emerging information on the diagnosis and management of patients with MM, but no more frequently than once every 6 months. The decision to update is made by the Russian Ministry of Health based on proposals submitted by medical professional non-profit organizations. The formulated proposals must take into account the results of a comprehensive assessment of drugs, medical devices, and the results of
Appendix A3. Reference Materials
Table 5. Assessment of antitumor response (combined IMWG and RECIST criteria)
Complete response | Complete disappearance of previously identified radiological abnormalities. For patients with secretory plasmacytoma, the absence of paraprotein in serum and/or urine. |
|---|---|
Very good partial response | Achievement of complete remission according to clinical and instrumental data, but detection of paraprotein in serum and/or urine by immunofixation / reduction of serum paraprotein secretion ≥ 90% / urinary paraprotein excretion < 100 mg/24h |
Partial response | Reduction of serum/urine paraprotein concentration by ≥50%. For extramedullary plasmacytoma, a 30% reduction in tumor diameter |
Stable disease | Failure to meet the criteria for partial remission or disease progression |
Progression | Appearance of new plasmacytomas or an increase in previously identified lesions by at least 20%; appearance of criteria for multiple myeloma; increase in paraprotein secretion by 25% or more from the lowest achieved value in serum and/or urine |
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Solitary plasmacytoma belongs to neoplastic diseases of the blood system and is characterized by localized involvement of an organ. The main test to confirm the diagnosis of SP is microscopic examination of a tissue sample obtained by biopsy of the affected organ. It is also necessary to perform comprehensive clinical, biochemical, and immunochemical blood and urine tests, peripheral blood lymphocyte immunophenotyping, PET/CT, MRI, or CT to determine the foci of tumor lesions, and bone marrow examination.
The main treatment method for SP currently is radiation therapy (RT), with the impact directed straight at the tumor-affected area. SP cells are extremely radiosensitive, which is why this treatment approach achieves a significant antitumor effect. RT eliminates the main clinical manifestations of the disease. In rare cases, when indicated, surgical treatment may be performed, and immunochemotherapy may also be discussed. After completing the treatment phase, the patient requires careful follow-up and monitoring by an oncologist/hematologist throughout life, along with timely diagnostic procedures to rule out disease recurrence.
Recommendations for the treatment of solitary plasmacytoma during pregnancy
Given the limited data on the management of pregnancy upon the manifestation of solitary plasmacytoma, the decision on the timing of initiation and the treatment regimen is determined individually involving an multidisciplinary team and a telemedicine consultation with specialists from federal medical institutions. If solitary plasmacytoma is diagnosed in the first trimester (up to 12 weeks) of pregnancy, it is advisable to consider the possibility of its termination.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Appendix G1. ECOG Performance Status Scale
Clinical assessment of the general condition of a patient with SP is performed using the scale developed by the Eastern Cooperative Oncology Group [25].
Original title: The ECOG Scale of Performance Status
Source: Oken M.M. et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group // Am. J. Clin. Oncol. 1982. Vol. 5, № 6. P. 649–65 [25]
Type: rating scale
Purpose: clinical assessment of the patient's general condition
Content (template) and key (interpretation):
Table 6. Clinical assessment of the patient's general condition
Status (scores) | Description of the patient's general condition |
|---|---|
0 | Fully active, able to carry on all pre-disease performance without restriction |
1 | Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work) |
2 | Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours |
3 | Capable of only limited self-care; confined to bed or chair more than 50% of waking hours |
4 | Completely disabled; cannot carry on any self-care; totally confined to bed or chair |
5 | Patient is dead |