The Use of Pomalidomide in the Treatment of Relapsed/Refractory Multiple Myeloma in Patients with Renal Failure

The present review includes data on efficacy and safety of pomalidomide, an immunomodulating 3rd generation drug used for treatment of relapsed and refractory multiple myeloma patients with renal failure. The results of multicenter randomized trials proved similar efficacy and comparable safety profile in patients with normal renal function and patients with moderate and/or severe renal failure. All patients received the standard starting dose. Pomalidomide dose needs to be reduced in response to hematological toxicity. The paper provides practical guidelines on the use of pomalidomide and treatment of adverse events adopted by consensus of international experts. Current approaches to multiple myeloma with renal failure, and the use of pomalidomide in particular, are demonstrated by means of a clinical case

Splenic B-cell marginal zone lymphoma with marked plasmocytic differentiation: tumor variant from Mott cells?

Splenic B-cell marginal zone lymphoma (SMZL) – a rare B-cell non-Hodgkin, s lymphoma, which is represented morphologically by mature lymphoid cells, corresponding to lymphocytes of secondary follicles marginal zone by immunological characteristics. Plasma cell differentiation can be in marginal zone lymphoma, but we described a single case of abundance of Mott cells as a tumor substrate in splenic B-cell marginal zone lymphoma.We present the first case of SMZL represented by Mott cells. This was the second case of Mott cells tumor described in Russia.This observation is the only case among the collected material of splenic lymphomas. The morphological pattern is characterized by marked proliferation of monoclonal lymphoid cells with plasma cell differentiation with presence of Mott cells and is evidence of intense intracellular secretion of immunoglobulins

Magnetic Resonance Imaging of Bone Marrow and its Results as a Criterion for Administration of Maintenance Therapy After Auto-HSCT in Multiple Myeloma Patients

Aim. To evaluate the efficacy of maintenance therapy in multiple myeloma (MM) patients after autologous hematopoietic stem cell transplantation (auto-HSCT) based on the results of MRI of bone marrow. Materials & Methods. The study included 32 MM patients aged 36 to 66 years (median 57 years) with complete remission after a single auto-HSCT. MRI of spine and pelvic bones was performed to identify the nature of bone marrow lesions and to determine the volume of tumor tissue on the day 100 after auto-HSCT. As maintenance therapy after auto-HSCT 14 patients received daily 15 mg lenalidomide in the period from day 1 to day 21 of the 28-day treatment course within 1 year. Monitoring of 18 patients was conducted without maintenance therapy. Statistical analysis included the assessment of progression-free survival (PFS) and relapse risk relationship to clinical and laboratory parameters. Results. Twenty patients had a positive MRI (tumor volume > 1 cm3). Zero variation of MR signal in bone marrow and detection of a < 1 cm3 tumor were regarded as a negative MRI, which was the case in 12 patients. After reaching the negative MRI the best rates of 2-year PFS were registered: 100 % with maintenance therapy and 84 % without maintenance therapy. In patients with tumor load on MR scans the 2-year PFS significantly (p = 0.03) varied and accounted for 80 % in patients who received maintenance therapy vs. 33 % in patients without maintenance therapy. Administration of maintenance therapy after detecting residual tumor on MR scans on day 100 after auto-HSCT has a positive effect on PFS rates. Multivariate analysis confirmed the residual tumor on MR scans of bone marrow to be the most important parameter PFS depends on. Conclusion. A negative MRI after auto-HSCT is a favourable prognostic factor determining a long-lasting (> 2 years) MM free period, despite the lack of maintenance therapy

Bone marrow MRI after autologous transplantation and the effect of residual tumor on progression-free survival of multiple myeloma patients

Background . The study of influence of residual tumor mass, determined by magnetic resonance imaging (MRI), on the progression-free survival (PFS) remains an actual problem. Since the visual assessment of tumor bone marrow lesion can be one of the criteria for the subsequent personalized treatment choice in multiple myeloma patients.The objective of study was to determine the effect of bone marrow lesions detected by MRI after autologous hematopoietic stem cells transplantation (auto-HSCT) on PFS in multiple myeloma patients.Materials and methods . The prospective study included 60 patients who underwent spine and pelvic bones MRI on the 100 th day after autoHSCT.Results . Focal bone marrow changes were found in 47 of them – from 1 to 56 lesions (mean 6 ± 9). Significant (p = 0.01) differences of PFS in multiple myeloma patients depending on the presence or absence of tumor mass on 100 th day after auto-HSCT were revealed: with MRI negative status, 2-year PFS was 89 % versus 50 % in a group of patients with residual tumor mass.Conclusion . MRI-negative status after auto-HSCT is a favorable prognostic factor contributing to prolonged disease-free survival

Current Multiple Myeloma Treatment Strategies with Novel Agents: A European Perspective

This review presents an overview of the most recent data using the novel agents thalidomide, bortezomib, and lenalidomide in the treatment of multiple myeloma and summarizes European treatment practices incorporating these novel agents

STUDY OF MINIMAL RESIDUAL DISEASE BY MULTICOLOR FLOW CYTOMETRY IN MULTIPLE MYELOMA AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

The frequency of achieving complete remission, as well as overall and disease-free survival, in multiple myeloma (MM) had increased due to introduction in MM treatment regimens of high-dose chemotherapy with following autologous hematopoietic stem cell transplantation (ASCT). However the number of relapses remains high, caused by persistence of residual tumor cells, i.e., the presence of minimal residual disease (MRD). One of the methods for MRD study is multicolor flow cytometry (MFC) where abnormal expression of surface antigens on myeloma plasma cells (PC) is determined. The aim of our study was to investigate the MRD by MFC before and after ASCT, the frequency of MRD-negative status achievement in complete remission (CR) patients at +100 days after ASCT and the frequency of abnormal expressed antigens on myeloma plasma cells. The study included40 MMpatients in CR at +100 days after ASCT and showed that the most common aberrations of PC were: abnormal absence of CD19 and/or CD27, decreased expression of CD38 and abnormal presence of CD56. The proportion of myeloma PCs from all bone marrow cells decreased significantly after ASCT: 20 % of patients acquired MRD-negative status, 10 % had a decrease in the number of abnormal PCs by one fold. Analysis of probability of immunochemical relapse showed that the worst prognosis was in patients with MRD-positive status before and after ASCT. During the MRD monitoring within 3-18 months, MRD-relapses were detected with the subsequent development of immunochemical relapse. The detection MRD in the dynamics is more informative than the study at only one step of therapy. It may help to select more adequate treatment for patient with multiple myeloma in each specific case

Daratumumab Monotherapy for Relapsed or Refractory Multiple Myeloma: Results of an Early Access Treatment Protocol in Europe and Russia

Introduction Daratumumab is a human IgGκ monoclonal antibody targeting CD38. Despite the demonstrated benefit of daratumumab in multiple myeloma, not all patients have access to commercially available daratumumab. Here we report a pooled analysis of patients from the UK, Spain, Italy, and Russia enrolled in an open-label, early access treatment protocol (EAP) that provided daratumumab (16 mg/kg) monotherapy to patients with heavily pre-treated relapsed or refractory multiple myeloma (RRMM). Methods Intravenous daratumumab 16 mg/kg was administered to patients who had received ≥ 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and an IMiD. Safety and patient-reported outcomes data were collected. Results A total of 293 patients received  ≥ 1 dose of daratumumab. The median duration of daratumumab exposure was 4.2 (range 0.03–24.1) months, with a median number of 13 (range 1–37) infusions. The overall response rate was 33.1%, and the median progression-free survival was 4.63 months. Grade 3/4 treatment-emergent adverse events occurred in 60.1% of patients, of which the most common were thrombocytopenia (18.8%), anemia (11.9%), and neutropenia (11.6%). The most common serious adverse events were pneumonia (4.4%) and pyrexia (4.1%). Infusion-related reactions occurred in 45.1% of patients. The median change from baseline in all domains of patient-reported outcome instruments (European Quality of Life Five Dimensions Questionnaire [EQ-5D–5L], European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ-C30], and EORTC Multiple Myeloma Module [QLQ-MY20]) was generally 0 or close to 0. Conclusion These EAP results are consistent with those from previous trials of daratumumab monotherapy and confirm its safety in patients from Europe and Russia with heavily pre-treated RRMM. Trial Registration ClinicalTrials.gov identifier, NCT02477891

Insights on multiple myeloma treatment strategies

The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future

Health-related quality-of-life results from the phase 3 OPTIMISMM study: pomalidomide, bortezomib, and low-dose dexamethasone versus bortezomib and low-dose dexamethasone in relapsed or refractory multiple myeloma

This is an accepted manuscript of an article published by Taylor & Francis in Leukemia & Lymphoma on 09/04/2020, available online: https://www.tandfonline.com/doi/full/10.1080/10428194.2020.1747066 The accepted version of the publication may differ from the final published version.In the randomized phase-3 OPTIMISMM study, the addition of pomalidomide to bortezomib and low-dose dexamethasone (PVd) resulted in significant improvement in progression-free survival (PFS) in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM), including lenalidomide refractory patients. Here, we report health-related quality of life (HRQoL) results from this trial. Patients received PVd or Vd in 21-day cycles until disease progression or discontinuation. HRQoL was assessed using the EORTC QLQ-C30, QLQ-MY20, and EQ-5D-3L instruments on day 1 of each treatment cycle. Mean score changes for global QoL, physical functioning, fatigue, side effects of treatment domains, and EQ-5D-3L index were generally stable over time across treatment arms. The proportion of patients who experienced clinically meaningful worsening in global QoL and other domains of interest was similar. These HRQoL results with PVd along with previously demonstrated improvement in PFS vs Vd continue to support its use in patients with RRMM.This work was supported by Celgene Corporation.Published versio