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Autologous stem cell transplantation for multiple myeloma patients whose myeloma-defining event was SLiM.

In 2014, the International Myeloma Working Group (IMWG) updated the criteria for diagnosing myeloma and added three additional criteria to the traditional Calcium elevation, Renal impairment, Anemia, Bone disease (CRAB) criteria, called the Sixty % marrow plama cells, Light chain ratio >60, Mri demonstates lytic lesions (SLiM) criteria (clonal bone marrow plasma cells ≥60%, involved to uninvolved free light chain ratio (FLCr) ≥100 and >1 focal lesion on magnetic resonance imaging (MRI)). We report on the outcomes of 30 patients who underwent autologous stem cell transplantation (ASCT) where th

How I treat elderly patients with plasma cell dyscrasias.

Plasma cell dyscrasias are a rare heterogeneous group of hematological disorders which are more prevalent in the older part of the population. The introduction of novel agents, improved understanding of disease biology and better supportive management have improved outcomes considerably and in the era of the aging population the question of how to best manage older patients with plasma cell dyscrasias has never been more relevant. Data on how to treat these patients comes mostly from subgroup analysis as they are underrepresented in clinical trials. This review will cover issues, available evi

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… In intermediate-fitness patients one should aim to achieve a balance between safety and efficacy by using doublets and or even low dose triplets. … Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. …

Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy.

Upfront high-dose therapy with melphalan (HDM) followed by autologous stem cell transplantation (ASCT) has established itself as a core treatment for newly diagnosed multiple myeloma (NDMM) patients in the past 30 years. Induction therapy, HDM-ASCT, and subsequent consolidation and maintenance therapy comprise the current fundamental framework for MM treatment. The introduction of anti-CD38 monoclonal antibodies such as daratumumab and isatuximab has changed the treatment paradigm for transplant-eligible NDMM patients in that quadruplets have become the new standard induction therapy. The trea

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… Until a few years ago, regimens for induction therapy commonly included a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and dexamethasone (a three-drug therapy—triplet). … More recently, the introduction of anti-CD38 monoclonal antibodies, daratumumab and isatuximab, has changed the treatment paradigm for transplant-eligible NDMM patients in that quadruplets have supplanted triplets [ 14 , 15 ]. 2.1. …

Novel Short PEG Chain-Substituted Porphyrins: Synthesis, Photochemistry, and In Vitro Photodynamic Activity against Cancer Cells.

This work presents the synthesis and characterization of metal-free, zinc (II), and cobalt (II) porphyrins substituted with short PEG chains. The synthesized compounds were characterized by UV-Vis, 1H and 13C NMR spectroscopy, and MALDI-TOF mass spectrometry. The origin of the absorption bands for tested compounds in the UV-Vis range was determined using a computational model based on the electron density functional theory (DFT) and its time-dependent variant (TD-DFT). The photosensitizing activity was evaluated by measuring the ability to generate singlet oxygen (ΦΔ), which reached values up

Review of patient-reported outcomes in multiple myeloma registrational trials: highlighting areas for improvement.

Over the past 13 years, there have been advances in characterizing the patient experience in oncology trials, primarily using patient-reported outcomes (PROs). This review aims to provide details on the PRO measures and analyses used in multiple myeloma (MM) registrational trials. We identified registrational trials supporting MM indications from 2007 to 2020 from FDA databases. Trial protocols, statistical analysis plans, and clinical study reports were reviewed for PRO measures used, collection methods, statistical analyses, baseline and instrument completion definitions, and thresholds for

Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up.

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… Based on the above data, VRd is likely to offer the best risk-benefit profile to date among triplet combinations (II, B). … Regarding induction therapy pre-ASCT, VRd is likely to offer the best risk-benefit profile to date among triplets based on bortezomib (II, B); however, VRd lacks direct comparisons with VTD or DaraVTD and is not licensed by the EMA. …

Evolving Paradigms in the Management of Multiple Myeloma: Novel Agents and Targeted Therapies.

Multiple myeloma (MM) is a clonal plasma cell disorder defined by bone marrow infiltration and osteolytic bone lesions and is the second most common hematologic malignancy after non-Hodgkin lymphoma. The landscape of MM treatment was transformed at the dawn of the twenty-first century by the introduction of novel agents including proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide), which have prolonged the survival of MM patients. The recently revised International Myeloma Working Group diagnostic criteria for MM added validated biomarkers (clonal bone mar

Уникальные диагностические и терапевтические функции порфиринов и фтальокянинов в области фотодинамической терапии, визуализации и термостимы.

Порфиринические молекулы играют уникальную тераностическую роль в лечении болезней; они используются для отображения, обнаружения и лечения различных форм заболевших тканей, в том числе в связи с возрастной маркулярной дегенерацией и рядом различных видов рака. В настоящее время основное внимание уделяется клинической съемке опухолей; целенаправленной доставке фотосенитеров и потенциалу фотоэнцедентов в мультимодальных биомедицинских наноплатформах. В настоящем Обзоре подчеркиваются роли порфириновых молекул в области съемки и пдта, а также исследования по совершенствованию их селективного пог

Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial.

CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65-79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) nega

Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase 2 trial.

Multiple myeloma (MM) patients typically receive several lines of combination therapy and first-line treatment commonly includes lenalidomide. As patients age, they become less tolerant to treatment, requiring convenient/tolerable/lenalidomide-free options. Carfilzomib and/or bortezomib-exposed/intolerant, lenalidomide-refractory MM patients with ≥2 prior lines of therapy were randomized 3:2 to ixazomib-dexamethasone (ixa-dex) (n = 73) or pomalidomide-dexamethasone (pom-dex) (n = 49) until progression/toxicity. Median progression-free survival (mPFS) was 7.1 vs 4.8 months with ixa-dex vs pom-d

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… In addition, for a patient population previously exposed to pom-dex-based triplets or those who have become refractory to pomalidomide, alternative and effective all-oral doublet options may be required. … Ixa-dex is an appropriate option for patients who cannot tolerate triplet combinations, or who are not able or prefer not to receive parenteral treatment administration, or who require a non-immunomodulatory drug-based treatment approach. …

Bone-modifying therapy in multiple myeloma: a comprehensive review.

Multiple myeloma (MM) is a clonal hematologic malignancy characterized by plasma cell proliferation in the bone marrow. One of the most common clinical presentations is skeletal-related events (SREs), characterized by osteolysis of the bone, leading to a significant morbidity and mortality. The main aim of this review article is to provide an overview of the pathogenesis and evidence-based, guideline-recommended treatment of SREs. MM bone homeostasis is altered by numerous pathways and cytokines, leading to the pathogenesis of bone and osteolytic lesions. Historically, bisphosphonates were the

Множественная миелома в реальной жизни: клиническая и прогнозирующая инфекция - опыт одного центра.

Второй пересмотр Международной системы уплотнения (R2-ISS) представляет собой прогнозную модель, разработанную у недавно диагностированных пациентов с несколькими миэлома (НДММ) в качестве показателя биологического риска, связанного с заболеваниями. Тем не менее на ход болезни также влияют факторы, связанные с пациентами. Слабая оценка Международной рабочей группы по миеломе (МРГМ) обеспечивает стандартную оценку пригодности пациентов и может дополнять стратификацию биологических рисков. Цель исследования состояла в том, чтобы проанализировать прогнозируемое значение системы баллов R2-ISS и сл

Steps towards a Multiple Myeloma Cure?

Multiple myeloma survival has increased in last 20 years because of new treatments, better clinical management due to novel diagnostic tools such as imaging, and better understanding of the disease, biologically and genetically. Novel drugs have been introduced that act with different therapeutic mechanisms, but so have novel therapeutic strategies such as consolidation and maintenance after autologous stem cell transplant. Imaging (such as PET-CT and MRI) has been applied at diagnosis and after therapy for minimal residual disease monitoring. Multiparametric flow and molecular NGS may detect,

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… Triplet and quadruplet combinations have demonstrated significative benefits when used in HR patients in many clinical trials [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. … Novel triplets and quadruplets are being tested, as is the monoclonal anti-CD38 antibody associated with bortezomib lenalidomide (Dara-VRD, GRIFFIN study, with 51% MRD negativity reported) [ 60 ]. …

Treatment-free interval as an additional measure of efficacy in a large UK dataset of transplant ineligible myeloma patients.

Treatment of transplant-ineligible (TNE) newly diagnosed multiple myeloma (NDMM) requires a balance between disease control and maintaining quality of life (QoL). Patients value treatment-free remission periods in this incurable condition, as they are associated with better QoL. We set out to study clinical outcomes of consecutive TNE NDMM patients in routine care treated in Thames Valley Cancer Network between 2009 and 2017. The primary outcome was the evaluation of the treatment-free interval (TFI) after 1st and subsequent lines of therapy in the total cohort and in individual subgroups, acc

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… ) | 16 (11%) | 4 (3%) | 9 (22%) | 3 (3%) | 0 (0%) Alkylator-based | 30 (10%) | 4 (3%) | 26 (18%) | 27 (66%) | 8 (9%) | 8 (9%) Combination regimen b | | ( n = 292) | ( n = 144) | ( n = 148) | ( n = 41) | ( n = 92) | ( n = 52) Doublet | 88 (30%) | 45 (31%) | 43 (29%) | 13 (32%) | 18 (20%) | 21 (40%) Triplet … Physicians’ choice of triplet over doublet regimen was comparable between age groups (≤75: 69%, >75years: 71%). The use of triplets over doublets was also evident in the different co-morbidity subgroups (CCI 0–2: 68% vs. CCI 3–4: 80% vs. CCI ≥5: 60%). …

The choice of regimens based on bortezomib for patients with newly diagnosed multiple myeloma.

IntroductionBortezomib has significantly improved multiple myeloma (MM) response rates, but strategies for choosing bortezomib-based regimens for initial MM therapy are not standardized. Here, we describe four bortezomib-based therapies in Chinese MM patients to determine the optimal chemotherapeutic approach.MethodsNewly diagnosed symptomatic MM patients at three hematological centers between February 1, 2006 and May 31, 2013 were treated with therapies including bortezomib plus dexamethasone (PD) or combinations of PD with either adriamycin (PAD), cyclophosphamide (PCD) or thalidomide (PTD)

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… At this time, regimens in China are mainly bortezomib-based therapies, including doublet regimens (PD), and triplet regimes such as PCD, PAD and PTD. Bortezomib, as a component of these protocols is given 1.3 mg/m 2 twice a week, or 1.5 mg/m 2 once a week. … Rajkumar SV. (2012) Doublets, triplets, or quadruplets of novel agents in newly diagnosed myeloma? Hematology Am Soc Hematol Educ Program. 354–361. 15. …

An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma.

Proteasome inhibition represents one of the more important therapeutic targets in the treatment of multiple myeloma (MM), since by suppressing nuclear factor-κB activity, which promotes myelomagenesis, it makes plasma cells susceptible to proapoptotic signals. Bortezomib, the first proteasome inhibitor approved for MM therapy, has been shown to increase response rate and improve outcome in patients with relapsed/refractory disease and in the frontline setting, particularly when combined with immunomodulatory drugs and alkylating agents. Among second-generation proteasome inhibitors, ixazomib (

Infection-related morbidity in a large study of transplant non-eligible newly diagnosed myeloma patients treated with UK standard of care.

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IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma.

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study.

Economic Evaluation of Adding Daratumumab to Carfilzomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma.

ObjectiveTo assess the cost-effectiveness of adding daratumumab to carfilzomib and dexamethasone (KdD) in patients with relapsed or refractory multiple myeloma (RRMM).Materials and methodsA Markov model was established to estimate health and economic outcomes of carfilzomib and dexamethasone (Kd) with or without daratumumab for RRMM patients over a lifetime horizon. The patients and intervention of the two arms were modeled according to the CANDOR trial. Costs were collected from the Chinese health system perspective. One-way sensitivity analysis and probabilistic sensitivity analysis were per

Natural History and Prognostic Factors at First Relapse in Multiple Myeloma.

The prognosis of multiple myeloma has considerably improved due to the introduction of novel agents in the upfront setting. However, the great majority of patients ultimately relapse, and choosing a salvage treatment at first relapse remains challenging. The natural history of first relapsed disease in the current era is also not well described. We retrospectively studied 300 patients with first relapsed myeloma seen between 2004 and 2019 from two institutes in Singapore. The median duration from diagnosis to first relapse was 22.7 months (1.1-97.0 months). Most patients received novel agent-b