Aim . To examine the role of very good partial response or better (VGPR+) as a surrogate predictor of progression-free survival (PFS) in multiple myeloma (MM) patients. Materials and methods . A systematic literature review of MEDLINE database (2010–2023) and materials presented at hematology and cancer congresses (2020–2022) was performed to identify studies reporting median progressionfree survival (PFS) and the rate of very good partial response (VGPR+). The study used Spearman’s weighted correlation and linear regression methods to analyze the association between median PFS and VGPR+. A total of 34,443 patients were involved in 182 original studies that included real-world clinical practice data. Results . Based on the number of patients or year of publication, the correlation between VGPR+ and median PFS was statistically significant (Spearman coefficient r = 0.61), but low. For refractory/recurrent MM (r = 0.69) and for monoclonal antibody therapy (r = 0.81), the correlation between VGPR+ and PFS was stronger. In addition to achieving VGPR+, the line of therapy and autologous stem cell transplantation also played an important role in determining PFS. Based on these factors, an increase of one percentage point in VGPR+ predicted a 0.21‑month increase in median PFS in the final adjusted linear regression model. Conclusion . In this study, VGPR+ was found to predict PFS, making it a universal early point of reference for MM prognosis regardless of the treatment type.

Graft failure (GF) is an extremely rare complication of autologous hematopoietic stem cell transplantation (auto-HSCT) with a frequency not exceeding 3–5 % of all cases of this technology. Primary graft failure is distinguished when restoration of hematopoiesis has not occurred by day +28 after hematopoietic stem cell transfusion, and secondary GF, implying the occurrence of neutropenia <0.5 × 109 /L after successful initial engraftment, which cannot be explained by tumor relapse, infections or chemotherapy toxicity.In this report, we present a clinical case of a 57-year-old woman with newly diagnosed diffuse large B-cell lymphoma with multiple lesions of the skeletal bones and lymph node involvement on both sides of the diaphragm. A feature of this case of diffuse large B-cell lymphoma was the secretion of monoclonal IgGκ and plasmacytoid differentiation of tumor cells. Firstline therapy with 6 cycles of R-CHOP was unsuccessful. A complete metabolic response according to positron emission tomography combined with computed tomography (PET/CT) was obtained after 2 cycles of second-line R-DHAP therapy, followed by myeloablative consolidation and transfusion of 16.9 × 106/kg CD34+ autologous hematopoietic stem cells. The patient was discharged from the hospital on day +15 with stable restoration of hematopoiesis. The pancytopenia and aplasia of bone marrow hematopoiesis developed across 3 months after auto-HSCT. For secondary GF, the patient received G-CSF, transfusions of blood components, and treatment similar to that for aplastic anemia (cyclosporine 5 mg/kg plus eltrombopag). A partial hematological response was obtained within 9 months, and a complete response by 24 months of therapy. According to PET/CT data 36 months after auto-HSCT, the patient had a local increase in the level of 18F-fluorodeoxyglucose fixation (maximum standardized uptake value 3.33), possibly of an inflammatory nature, in the body of the L4 vertebra on the background of bone cement after vertebroplasty performed at the onset of the disease. In addition, monoclonal secretion of IgGκ persists in the absence of immunomorphological evidence of bone marrow involvement.In conclusion, the article discusses the possible causes of the monotonous monoclonal IgGκ secretion and presents a literature review of known GF treating methods.

AIM. To develop an information and retrieval system for hematologists which would enable effective decision making in multiple myeloma (MM) treatment through simulation and prediction of response to therapy considering a patient’s clinical profile-related characteristics and based on the analysis of data from public science sources. MATERIALS & METHODS. The analysis included 145 therapeutic options and 56,217 MM patients enrolled in 311 clinical studies, the results of which were published in the medical literature from 2003 to 2024. To simulate therapy scenarios, the Monte Carlo method was used for calculating the probability of achieving very good and even better partial response in patients with different characteristics that define not only their clinical profile but also the chemotherapy variants. RESULTS. This study introduces an interactive online application called М-BОТ (available at oncotriage.ru) enabling to predict response to therapy under certain specified conditions and to visualize the result as real-time ranking of therapeutic options via the user interface. Apart from a patient’s clinical profile-related characteristics underlying MM treatment decision making, it is possible to select trials by their types and numbers of patients enrolled. CONCLUSION. The therapy recommendations resulted from simulation of different MM therapy scenarios with the use of the Monte Carlo method considerably extend the potential for rapid retrieval of reliable science information which would confirm the optimal choice of a therapeutic option in the given clinical setting. In future, this approach can be regarded as a basis for building up a support system in individual and consensus decision making. It will allow for predicting the efficacy of multi-stage MM treatment strategies with several therapy lines and their safety as well.

Pomalidomide is a third-generation immunomodulatory drug (IMiD) that has taken an important place in the management of relapsed/refractory multiple myeloma (RRMM) including in patients with resistance to lenalidomide (R). Synergism of antitumor activity was obtained by combining pomalidomide with dexamethasone (Pd), proteasome inhibitors (PIs), and monoclonal antibodies directed against CD38 and SLAMF7 receptors. The dose-limiting toxicity of pomalidomide is neutropenia (4860% grade 3 for a dose of 4 mg/day). Overcoming resistance to lenalidomide is seen as a key benefit of pomalidomide in the development of triplets that can be used in 2nd and subsequent lines of RRMM treatment. In OPTIMISMM study (phase III), 70% of patients were lenalidomide resistant. Randomization was performed on VPd (bortezomib-Pd) and Vd (bortezomib, dexamethasone) therapy. Vd as control was implemented in two related phases III trials ENDEAVOR (carfilzomib, dexamethasone) and CASTOR (daratumumab-Vd). For patients with resistance to lenalidomide, the median progression-free survival (PFS) was 9.5 mon for VPd in OPTIMISMM; 9.3 mon in CASTOR (resistant to R 21%) for DVd, and 9.3 mon in ENDEAVOR (21%) for Kd - 8.6 mon. The ICARIA-MM study (phase 3; resistance to R 94%) demonstrated the benefit of incorporating isutaximab into the triplet (median PFS 11.1 and 5.9 mon for Isa-Pd and Pd respectively; p0.0001). Similar data were obtained in the ELOQUENT-3 study (phase II; resistance to R - 90%) for elotuzumab (10.3 and 4.7 mon for EPd and Pd respectively; p=0.008). In the APOLLO study (phase III; resistance - 80%), the efficacy of the triplet with daratumumab was confirmed (12.4 and 6.9 mon for DPd and Pd respectively; p = 0.0018). In the present review, the focus is on the consideration of treatment regimens that are of relevance to Russian clinical practice.

Anaplastic large cell lymphoma is a rare form of non-Hodgkin's lymphoma that requires an early diagnosis and urgent therapy due to aggressive tumor process. Clinically, most non-Hodgkin's lymphoma present with lymphoadenopathy and В-symptoms (such as weakness, drowsiness, fatigue, subfebrile fever, profuse night sweats). However, anaplastic large cell lymphoma may present with nonspecific skin lesions with minimal or no B-symptoms. The skin lesions are heterogeneous, which may also delay verification of the diagnosis. We present a case of widespread anaplastic large cell lymphoma skin lesions mimicking a case of erysipelas, which progressed rapidly from a single rash on the wrist to an extensive lesion of the right breast within 1 month. Prior to verification of the diagnosis, the patient was treated for erysipelas, pyoderma, and herpes zoster with no response to therapy. Immunohistochemical examination of a skin biopsy confirmed the diagnosis of ALK-negative anaplastic large cell lymphoma. At the time of publication, the patient had completed 1 course of the CHOEP regimen, and 6 cycles of the program were planned. Our case demonstrates the necessity of a broad differential diagnosis of rashes torpid to the current therapy.

Most patients with multiple myeloma (MM) suffer from chronic pain of varying degrees of intensity at every stage of the natural disease process. Osteolytic bone lesions are one of the most common complications of MM. The bone disease visualized by PET/CT and MRI affects up to 90% of newly diagnosed MM patients, increasing the risk of the development of skeletal-related events. Pathological fractures and spinal cord compression occur in 17% and 6% of patients, respectively. Bone pain is explained by an increase in pressure in the bone marrow, the release of chemical mediators by myeloma plasma cells, and the occurrence of microcracks in the bones, indirectly to a violation of local metabolism. Management of myeloma bone disease includes anti-myeloma chemotherapy and radiotherapy, antiresorptive therapy with bisphosphonates or denosumab, and direct pharmacological pain correction. Patients with pathological vertebral fractures and without spinal cord compression should be considered for vertebroplasty or kyphoplasty. The use of proteasome inhibitors and monoclonal antibodies for the treatment of MM is associated with a risk of herpes simplex virus (HSV) and varicella-zoster virus (VZV) reactivation. The result of the healing of herpetic eruptions in some patients will be the development of postherpetic neuralgia, manifested by excruciating pain for months or years. Moreover, the treatment with proteasome inhibitor bortezomib is often associated with the development of long-term persistent peripheral neuropathy, often complicated by pain. According to their neurobiological and clinical features, pain is classified into nociceptive, neuropathic, and functional. Bone pain is nociceptive and for postherpetic and chemotherapy-induced neuropathy, the neuropathic component is more significant. Opioids are the drugs of choice for moderate to severe nociceptive pain, while anticonvulsants and antidepressants are the most commonly used adjuvants for neuropathic pain. This review summarizes information on the pathophysiology of various types of pain syndrome in patients with MM, as well as on modern approaches to the prevention and treatment of complications. The issues of the pharmacology of opioid analgesics are discussed. The review concludes with data from a clinical trial of a new domestic non-opioid μ1-opioid receptor agonist Tafalgin, considered a real alternative to narcotic analgesics.

Key Points • EFS was meaningfully improved with enasidenib vs CCR; OS was confounded by early dropout and use of subsequent AML therapies.• Enasidenib provided meaningful morphologic and hematologic responses vs CCR in this heavily pretreated older R/R mutant-IDH2 AML population.

Currently, lenalidomide is the only immunomodulatory drug (IMiD) approved for maintenance therapy in patients with newly diagnosed multiple myeloma who have received high-dose chemotherapy and autologous stem cell transplantation (ASCT). The maintenance with lenalidomide showed an advantage over placebo or observation for both progression-free and overall survival in a series of phase 3 randomized trials. Salvage ASCT can be performed after disease relapse in case of a long-term response after the first transplantation or if this option has not been performed before. Pomalidomide is a third-generation IMiD approved for the treatment of relapsed and refractory multiple myeloma, which is efficient in patients with resistance to lenalidomide and proteasome inhibitors. Structurally, lenalidomide and pomalidomide are similar, and therefore the latter can also be considered as a drug for maintenance, however, there are no relevant phase 3 randomized trials. In this article, we present a clinical case of a 60-year-old patient with newly diagnosed multiple myeloma who progressed after 2 lines of induction therapy, which included lenalidomide and two proteasome inhibitors (bortezomib, ixazomib). The use of Pd combination (pomalidomide, dexamethasone) made it possible to achieve a repeated response and implement of salvage ASCT. The second ASCT was carried out only 12 months later after the first due to the COVID-19 pandemic. Subsequent long-term maintenance therapy with pomalidomide resulted in a complete response and minimal residual disease negativity. The resulting response has persisted at the time of this writing for over 2 years. To discuss the presented clinical case, the data of the French phase 2 IFM 2013-01 study were used, in which patients with failed first-line transplantation in case of relapse received PCd (pomalidomide, cyclophosphamide, dexamethasone) induction, salvage ASCT, and maintenance by Pd until disease progression. Pomalidomide may be an acceptable substitute for lenalidomide in patients with prior intolerance or refractory to this IMiD.

Analysis of treatment results of 165 primary adult patients with diffuse B large-cells lymphoma (DBLCL) treating in Moscow municipal clinics is presented. Study aimed on analysis of efficacy of various dose intensity chemotherapy schedule according to disease molecular genetics variants. 28 adolescents and young adults (median age — 21.7 years) have received treatment according to pediatric BFM-NHL 90m and BFM-NHL 2004M protocols, 46 (median age — 29.0 years) and 91 (median age — 59.5) adults according to courses CHOP and R-CHOP, respectively. It was not randomized study. Germinal and postgerminal variants DBLCL were determined using immunohistochemical technique for 58 (35%) patients with appropriate primary samples. For young patients with germinal DBLCL therapy superiority of intensive BFM-NHL 90m and B-NHL 2004M protocols in relation to postgerminal variants was revealed: 5-years event-free survival (EFS) was 1.0 ± 0.0 (n = 6) versus 0.44 ± 0.15 (n = 9), respectively (p 0.05). Data receiving proves expediency of treatment adolescents and young adults with DBCLC from germinal center cells according to intensity BFM-like protocols.

Proteasome inhibitors and immunomodulators (IMiDs), primarily bortezomib and lenalidomide, are essential components of treatment for both newly diagnosed and relapsed/refractory multiple myeloma (MM), producing high response rates and resulting in improved overall survival. However, bortezomib often induces a dose-limiting toxicity in the form of peripheral neuropathy (PN). Neurotoxicity often affects patient’s quality of life and requires dose modification or withdrawal of therapy, with a possible effect on the overall response. A prompt recognition of predisposing factors (such as diabetes mellitus, vitamin B12 deficiencies, or viral infections) and appearance of signs and symptoms, through a periodic neurological assessment with appropriate scales, is extremely important. Usually, bortezomib-induced PN is a sensory axonopathy characterized by numbness, tingling, and severe neuropathic pain in stocking and glove distribution while motor neuropathy is less frequently observed. Dose adjustment of bortezomib could be necessary during treatment. Anticonvulsants (pregabalin, gabapentin, carbamazepine, etc.) and tricyclic antidepressants (amitriptyline) are most often used to relieve neurological pain. In this review we focus on the clinical manifestations of bortezomibinduced PN, current understanding of the pathophysiological mechanisms as well as clinical and pharmacological aspects of prevention and management this complication. New proteasome inhibitors such as ixazomib and carfilzomib do not have the neurotoxicity of bortezomib. An early switch within the class of proteasome inhibitors from bortezomib to oral ixazomib appears to be an important approach to prevent severe PN. Our own clinical case of an early switch from bortezomib-based induction to IRd triplet (ixazomib, lenalidomide, dexamethasone) is cited as an illustration of the success of this approach.

This report describes the case of a 43-year-old Caucasian man with a 6-year history of hematological abnormalities associated with arterial hypertension, primary hypercholesterolemia, and obesity. The patient presented with facial redness, low erythropoietin level, negative tests for JAK2V617F, an exon 12JAK2 mutations, and mutations associated with congenital erythrocytosis; no signs of splenomegaly were found. Only regularly performed phlebotomy, but not getting blood pressure under control made it possible to lower hematocrit and hemoglobin levels.

Introduction. Immunomodulatory drugs (IMiDs) are a class of chemical derivatives of thalidomide with numerous immunomodulatory, antiangiogenic, anti-inflammatory, and cytostatic effects in multiple myeloma (MM).Aim — to highlight the history of the discovery of IMiDs and discuss the molecular mechanisms of their therapeutic activity.Basic information. In 2010, more than half a century after the German company Chemie Grünenthal began the clinical use of thalidomide, the first understanding of the molecular mechanism of thalidomide and its structural derivatives appeared. Hiroshi Handa and colleagues from the Tokyo Medical University discovered that the drug thalidomide binds to the protein Cereblon (CRBN), a substrate receptor of the CRL4CRBN E3 ubiquitin ligase. Subsequent generations of immunomodulatory drugs (IMiDs) — lenalidomide and pomalidomide, are structurally like thalidomide. The glutarimide ring of IMiDs is inserted into the receptor pocket of the CRBN. In this case, the variable phthalimide part of the drug protrudes from the binding domain, changing the configuration of the CRBN in such a way that it allows it to interact with proteins (neosubstrates) with which it does not react under physiological conditions. It was later found that ubiquitin-mediated degradation of two transcription factors (Ikaros and Aiolos) underlies the antitumor and immunomodulatory activity of IMiDs, which have shown unique clinical efficacy in the treatment of multiple myeloma. A natural continuation of the success of IMiDs was the creation of a series of therapeutic molecules (Iberdomide, etc.) belonging to a new class of drugs called CELMoDs (Cereblon E3 Ligase Modulating Drugs). The presented literature review is devoted to the history of the discovery of IMiDs and a discussion of the molecular mechanisms of their therapeutic activity.

Immunomodulatory preparations (IMP) — lenalidomide (СС-5013, Revlimid®) and pomlidomide (CC-4047, Actimid®) — a new class of the medical products which are thalidomide synthetic derivatives. In comparison with initial compound they possess higher therapeutic activity and the optimized profile of toxic complications. In this review modern data on IMP antitumor activity with reference to multiple myeloma therapy are presented. Results of clinical study of lenalidomide in first-line therapy, in relapsed/refractory multiple myeloma and as a maintenance therapy after transplantation are shown.

Lymphoblastic lymphoma (LBL) is one of predominant childhood non-Hodgkin’s lymphoma (NHL) subtypes and consists 25—30 %. The study purpose was to investigate outcomes in children and adolescents with LBL treated with protocol NHL-BFM-90 and 95 in the Moscow region. 58 primary patients (m–40, f–18) with T- and B-LBL were enrolled from 05. 1991 to 08. 2008 (aged 1.5–21.6 years; median 11.0 years). Fifty-two (90 %) patients were treated with ALL-like therapy protocol NHL-BFM-90 or 95 for non-B-NHL and 6 (10 %) — NHL-BFM-90 for B-NHL. The complete response (CR) rate was 94 and 83 %, respectively. 5-years event-free survival (5y-EFS) was 0.80 ± 0.06 (median of observation 4.1 years) and 0.67 ± 0.19 (5.1 years), respectively (p > 0.05). 5-years overall survival (5y-OS) was 0.85 ± 0.05 and 0.80 ± 0.06 respectively (p > 0.05). The situation without mediastinal involvement was a factor unfavorable prognosis for T-LBL: 5y-EFS — 0.56 ± 0.17 vs. 0.90 ± 0.05 (p = 0.036). Thus the NHL-BFM-90 and 95 for non-B-NHL protocols are effective therapeutic regimes for pediatric LBL and obtained long-term results are comparable with international data.

Anemia is one of the most common symptoms of hematological malignancy and, on the other hand, a common complication of myelosuppressive anticancer therapy. Iron, vitamin B12, folate, biological analogs of human erythropoietin (EPO), and new targeted drugs (lenalidomide, luspatercept, roxadustat, etc.) are used in clinical practice to correct anemic syndrome in cancer patients. All these activators of erythropoiesis are combined into a single group called erythropoiesis-stimulating agents (ESAs). Issues of physiological regulation of erythropoiesis, historical information on the creation of recombinant human erythropoietin (rh-EPO), structural and biological characteristics of this group of drugs are covered in this literature review. In accordance with ESMO guidelines (2018), rh-EPO is indicated for patients receiving myelosuppressive chemotherapy with symptomatic anemia with Hb < 100 g/L and asymptomatic anemia with Hb < 80 g/L. ESAs are not used in patients not receiving chemotherapy, similarly to ASCO/ASH (2019) guidelines. Iron replacement therapy in patients receiving rh-EPO should be used regardless of whether there is an initial iron deficiency or not, since its functional deficiency occurs during treatment. The low-risk MDS is exception, where rh-EPO may be the mainstay of therapy. Low-risk MDS patients with endogenous EPO levels < 500 mIU/mL and a low transfusion load of less than 2 RBCs per month are optimal candidates for rh-EPO therapy. The article is illustrated by clinical observation of a patient with R-IPSS intermediate-risk MDS treated with epoetin alfa. The problems of prevention of thromboembolic complications associated with the use of ESA are also discussed.

The purpose of this study was evalueted of a long-term treatment outcome in chronic myeloid leukemia (CML) patients in accelerated phase treated with GlivecR and determination of an optimum therapy schedule. 105 patients (men — 46, women — 59) at the age from 15 till 74 years (a median age — 40 years) enrolled between 02.2001 and 02.2007 were studied. Treatment started a dose of 600 mg/day. At the insufficient primary therapy response or loss complete hematological and/or complete cytogenetic remission in the course of treatment, dose have been increased to 800 mg/day. In 82 (78.1%) patients complete hematological remissions have been reached. In 44 (41.9%) patients complete cytogenetic response (CR) is received, and in 27 (61.4 %) of them with molecular response: complete — 17 (63%) and major — 10 (27%). 6-year overall survival rate (OS) was 61.9%, 6-year event-free survival rate (EFS) — 30.5%. Achievement of complete CR was a predictor of long longterm survival rate: OS — 95.5% versus 37.7 % (р <0.001). In case of absence CR (n=16) imatinib dose escalation allowed to receive complete CR in 5 (31.25%) and minor — in 4 (25.0%) patients. Loss or absence of complete CR on imatinib therapy not always leads to CML progression: in 18 (17.1 %) patients without complete CR hematological parameters remain normal and there are no signs of disease progression.

Clinical efficacy of DAL-HD-90m protocol in the treatment of adolescent and young patients with Hodgkin's lymphomas was analyzed. From November 1997 to April 2007, 97 patients (38 males and 59 females) aged from 15 to 45 years with first diagnosed Hodgkin's lymphomas were enrolled to trial. Patients with IA, IB and IIA stages (therapeutic group (TG) 1) were treated by 2 cycles of ODPA regimen (vincristine, procarbasine, prednisolone, adriamycin) for females and 2 cycles of OEPA regimen (vincristine, ethoposide, prednisolone, adriamycin) for males. Patients with IIB, IIIA, IE A, IE B, IIE A stages (TG 2) received additional two cycles of multi-agent chemotherapy with COPD regimen (cyclophosphamide, vincristine, prednisolone, adriamycin). Patients of TG 3 (stages IIIB, IVA, IVB, IIE B, IIIE A, IIIE B) were treated with 2 cycles of ODPA and 4 cycles of COPD regimens irrespective of the patient's sex. Radiotherapy was carried out to all patients: targets included regional lymph nodes (total local dose of 30 Gy) and additionally the residual tumor (total dose of 6-10 Gy). Complete response was achieved in 91 % patients from TG 1, 94% patients from TG 2 and 89% from TG 3 group. Six-year overall survival was 0,91±0,09; 0,88±0,08 and 0,76±0,08, respectively. The absence of CR/CRu after 2 courses of OPPA/OEPA (0,60 versus 0,93; p=0,006), initial tumors of larger volumes than 50 cm3 (0,66 versus 0,91, p=0,017) and the International Prognostic Index no lower than 4 points (0,44 versus 0,82; p=0,039) were unfavorable prognostic factors for TG3 patients in this study.

Introduction. The COVID-19 pandemic has challenged health professionals and patients suffering from haematological diseases with embarrassed diagnosis, treatment, surveillance, social distancing and other constraints.Aim — addressing therapy for immune thrombocytopenia (ITP) during the COVID-19 pandemic in the light of own experience, as well as national and international professional medical community guidelines.Main findings. A standard choice in COVID-19-negative ITP patients are conventional, e.g., glucocorticosteroid (GCS) and intravenous immunoglobulin therapies. An early transfer to thrombopoietin receptor agonists (rTPO) appears optimal as reducing the infection risk in GCS withdrawal and significantly improving the stable remission rate without supportive treatment. Combined ITP–COVID-19 patients should consider a prednisolone treatment of 20 mg/day, provided an absent active bleeding. The dose may increase to 1 mg/kg/day in no response after 3–5 days. ITP patients admitted for COVID-19 should start weight‐based LMWH thromboprophylaxis upon attaining a platelet count of ≥ 30 × 109 /L. Chronic ITP patients should carry on usual treatment with standard SARS-CoV-2 preventive and social distancing measures. We exemplify three contrasting clinical cases of COVID-19-comorbid thrombocytopenia and discuss the ITP differential diagnosis and therapy. Two patients received GCSs and rTPO agonists (romiplostim, eltrombopag), while GCSs alone provided for platelet response in the third case. All patients showed a good clinical and biological response. Issues in SARS-CoV-2 vaccination are discussed.