Efstathios Kastritis

National and Kapodistrian University of Athens | uoa · Division of Clinical Therapeutics

Background/Objectives: Survival rates for ovarian cancer remain distressingly low. Despite established prognostic factors, the need to identify modifiable parameters to influence survival outcomes is imperative. Overweight and obesity, both prevalent conditions, have been implicated in cancer development and potentially poor survival. However, conf...

The purpose of the study was to investigate the effects of exercise training on the bone marrow immune microenvironment and on minimal residual disease of multiple myeloma patients who completed first‐line induction treatment. Eight multiple myeloma patients underwent 5 months of exercise training along with standard medical treatment. Eight age‐ a...

This meta‐analysis examined the association between minimal residual disease (MRD) negativity and survival outcomes in 15 304 patients with multiple myeloma (MM) enrolled in randomized controlled trials published until June 2, 2024. Overall, there was a significant, negative and strong association between MRD negativity odds ratios and survival haz...

Waldenström macroglobulinemia is an indolent B-cell lymphoma which although remains incurable, there are a lot of treatment options. Today, Bruton tyrosine kinase inhibitors have a central role in the management of the disease either as monotherapy or combination with other regimens, due to their efficacy, ease of administration, and safety profile...

Background: Serum B‐cell maturation antigen (sBCMA) levels have emerged as a potential biomarker for disease monitoring in multiple myeloma (MM) with prognostic value. Methods: Herein, we evaluated the sBCMA levels in 166 patients with newly diagnosed MM with an Elecsys‐based sBCMA assay. Results: Increased sBCMA levels at diagnosis were correlated...

Background/Objectives: Monoclonal gammopathies, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM), are conditions marked by the overproduction of specific monoclonal proteins. Patients with these conditions are known to have a higher risk of fractures compared to the general population, yet ther...

Importance Kidney light chain (AL) amyloidosis is associated with a risk of progression to kidney replacement therapy (KRT) and death. Several studies have shown that a greater reduction in proteinuria following successful anticlonal therapy is associated with improved outcomes. Objective To validate graded kidney response criteria and their assoc...

TEMPI syndrome is a rare, acquired disorder with multisystemic manifestations. It is classified as a plasma cell disorder and is characterized by telangiectasias, erythrocytosis, monoclonal gammopathy, perinephric fluid collections and intrapulmonary shunt. Even though TEMPI’s pathophysiology remains elusive, it responds to anti-myeloma therapy ind...

Immunocompromised patients with hematologic diseases may experience life-threatening infections with rather uncommon manifestations. Laryngitis has been described as a potential infection in such vulnerable patients and may result in major complications, ranging from impending airway obstruction to total laryngeal necrosis. Immediate laryngoscopy i...

Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM). We identified 54/4352 MM patients (1.2%), who developed CNS‐MM between 2000 and 2022. A matched‐control group of MM patients without CNS‐MM was used for comparisons. Median age was 63 years. Median time to CNS‐MM was 28 months; 6/54 experienced...

There is growing interest in multiple myeloma (MM) circulating tumor cells (CTCs), but their rareness in peripheral blood (PB) and inconsistency in cutoffs question their clinical utility. Herein, we applied next‐generation flow cytometry in 550 bone marrow (BM) and matched PB samples to define an optimal CTC cutoff for both transplant‐eligible and...

Several non‐coding RNAs are known to be associated with the pathobiology and progression of multiple myeloma (MM). ciRS‐7 (also known as CDR1‐AS), a key oncogenic circular RNA (circRNA) that sponges miR‐7‐5p and other cancer‐related microRNAs, was recently found to be downregulated in malignant plasma cells resistant to immunomodulatory drugs. Cons...

7530 Background: Ocular adverse events (OAEs, best corrected visual acuity [BCVA] change from baseline and keratopathy) are common with belantamab mafodotin (belamaf; GSK2857916) and often necessitate an ophthalmic exam to guide dosing. Herein, we evaluate a novel approach for belamaf dose modifications in transplant ineligible patients (pts) with...

Immunoglobin light chain (AL) amyloidosis is a rare disease characterized by organ deposition of amyloid fibrils, most commonly in the heart and kidney. Disease heterogeneity necessitates organ-specific assessment to determine prognosis and response or progression. To facilitate development of new therapies, the Amyloidosis Forum (a public-private...

While the current approach to precursor hematologic conditions is to “watch and wait,” this may change with the development of therapies that are safe and extend survival or delay the onset of symptomatic disease. The goal of future therapies in precursor hematologic conditions is to improve survival and prevent or delay the development of symptoma...

Background/aim: The presence of a monoclonal gammopathy of undetermined significance (MGUS) even in small amounts may trigger tissue damage through immunological or other mechanisms, irrespective of the potential for malignant transformation. The aim of the study was to present a case of monoclonal gammopathy of clinical significance with ocular m...

Despite the substantial progress in multiple myeloma (MM) therapy nowadays, treatment resistance and disease relapse remain major clinical hindrances. Herein, we have investigated tRNA‐derived fragment (tRF) profiles in MM and precursor stages (smoldering MM/sMM; monoclonal gammopathy of undetermined significance/MGUS), aiming to unveil potential M...

Background There is growing interest in multiple myeloma (MM) circulating tumor cells (CTCs), but its rareness in peripheral blood (PB) and inconsistency in cutoffs question their clinical utility. Herein, we aimed at defining the optimal CTC cutoff using a highly sensitive approach. Moreover, we analyzed matched bone marrow (BM) and PB samples in...

Preclinical and clinical data demonstrate synergy between belantamab mafodotin (belamaf) and immunomodulatory drugs with limited overlapping toxicities. We investigated the safety and efficacy of belamaf with lenalidomide 25mg on days 1-21 every 28 days and dexamethasone 40mg weekly (belamaf-Rd) in transplant ineligible patients with newly diagnose...

Waldenström macroglobulinemia (WM) is characterized by the expansion of clonal lymphoplasmacytic cells; the MYD88L265P somatic mutation is found in >90% of patients, but malignant B cells may still display intra‐clonal heterogeneity. To assess clonal heterogeneity in WM, we generated and performed single‐cell RNA sequencing of CD19⁺ sorted cells fr...

Haemostatic abnormalities and deregulated coagulation are common complications in AL amyloidosis. The relevant risks of thromboembolic and haemorrhagic events have not been thoroughly evaluated. To describe clinically significant thrombotic/haemorrhagic events in 450 consecutive patients with AL amyloidosis. Venous thromboembolic events (VTEs) were...

The use of lenalidomide in frontline therapy for patients with newly diagnosed multiple myeloma (MM) has increased the number of those who become refractory to lenalidomide at second line. In this context, we assessed the efficacy of daratumumab in combination with ixazomib and dexamethasone (Dara‐Ixa‐dex) in the prospective phase 2 study DARIA. El...

Circular RNAs (circRNAs) are associated with the pathobiology of multiple myeloma (MM). Recent findings regarding circCCT3 support its involvement in the development and progression of MM, through microRNA sponging. Thus, we aimed to examine the expression of circCCT3 in smoldering and symptomatic MM and to assess its clinical importance. Three cel...

Background/Aim: Waldenström’s macroglobulinemia (WM) is a rare slow-growing B-cell lymphoma that is characterized by lymphoplasmacytic bone marrow infiltration and the production of monoclonal immunoglobulin M (IgM) paraprotein. In 5-10% of patients, WM undergoes transformation into diffuse large B-cell lymphoma (DLBCL), which is more aggressive, w...

Aims Complete hematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work, and their prognostic significance. Methods and Results S...

Teclistamab shows promising results in R/R AL amyloidosis, with VGPR or better in 88% of patients and involved FLC < 10 mg/L in 76%. We observed a 35% rate of severe infections and no cardiac or kidney related events.

Introduction Renal impairment (RI), a common complication of multiple myeloma (MM), is associated with increased risk of early death. Reversal of MM-associated RI is a key predictor of improved survival. Regimens containing bortezomib and dexamethasone are the treatment backbone for newly diagnosed (ND) patients (pts) with MM and severe RI, even th...

Introduction: Teclistamab (TEC) is a bispecific BCMA-CD3 directed T-cell antibody (BsAb), recently approved by EMA and FDA. Approval was based on the MajesTEC-1 study showing high overall response rates (≥PR in 63.0%) in heavily pretreated patients with relapsed multiple myeloma (RRMM). Few reports have described Real-World experience despite that...

Introduction: Waldenström macroglobulinemia (WM) is an IgM-secreting lymphoplasmacytic lymphoma. CXCR4 somatic mutations are common in WM and are associated with clinical resistance to Bruton's tyrosine kinase (BTK) inhibitors and other therapeutic agents. CXCR4 mutations occur nearly exclusively with MYD88 L265Pmutation, with CXCR4 S338X constitut...

Introduction Belantamab mafodotin (belamaf; GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen, has shown promising efficacy and a favorable tolerability profile in the treatment of multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with be...

Introduction Relapse in patients (pts) with multiple myeloma (MM) is a common occurrence, resulting in a continued need for novel treatment approaches. Isatuximab (Isa), a monoclonal antibody (mAb), combined with pomalidomide (Pom) and dexamethasone (Dex), is indicated for the treatment of pts with relapsed/refractory multiple myeloma who have rece...

Background: AL amyloidosis is a rare disorder in which deposition of insoluble amyloid fibrils composed of misfolded light chains in vital organs, such as the heart or kidney, leads to serious and life-threatening organ dysfunction. Cardiac involvement is the primary determinant of clinical outcomes for patients with AL amyloidosis, and survival ex...

Background: Hypercoagulability is a common blood alteration in newly diagnosed chemotherapy naïve patients with multiple myeloma. Multiple myeloma (MM) figures among malignancies that significantly increase the risk of venous thromboembolism (VTE). The rate of VTE is higher at the time of diagnosis and during the first months following initiation o...

Backround: Thromboembolism occurs in about 10% of patients with multiple myeloma (MM). The incidence of VTE is higher in newly diagnosed MM patients as compared to those with relapsed or refractory disease and it is higher during the first 3 to 6 months after the initial diagnosis and treatment initiation. Some of the treatments administered to pat...

Introduction Belantamab mafodotin (belamaf) targets B-cell maturation antigen (BCMA) expressing plasma cells (PCs) and is approved for heavily pretreated patients (pts) with relapsed/refractory (RR) multiple myeloma. Clonal PCs in light-chain (AL) amyloidosis also express BCMA; thus, belamaf could be a treatment option for RRAL amyloidosis pts. We...

Background: Liver involvement in light chain amyloidosis (AL) is seen in up to 20% of patients and is typically encountered as part of multi-organ involvement. Liver involvement is associated with a poor prognosis. The goal of this study was to assess the prognostic impact of the hepatic response criteria, which were published in 2005 and were not...

Introduction Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen-binding antibody-drug conjugate approved as a monotherapy in pretreated patients (pts) with relapsed/refractory multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belamaf an...

Novel immunotherapies in AL amyloidosis (AL) are associated with improved outcomes while the use of ASCT in selected patients can offer long term remissions. Since the plasma cell clones are usually small or modest, sustained hematologic remissions are not uncommon in AL amyloidosis; however, the “curability” of the disease remains to be demonstrat...

Introduction Patients (pts) with Mayo stage 3B light-chain (AL) amyloidosis have high risk of early death, mainly due to severe cardiac dysfunction. The ANDROMEDA study showed that pts with newly diagnosed (ND) AL amyloidosis, daratumumab (dara) combined with bortezomib-cyclophosphamide-dexamethasone (D-VCd) induced high rates of hematologic comple...

Central Nervous System Multiple Myeloma (CNS-MM) is a rare but aggressive complication of MM, and its treatment remains an unmet clinical need. Herein we present a real-world national analysis of incidence, characteristics, prognostic factors and outcome of a large cohort of patients with CNS-MM. We evaluated 53 patients with CNS-MM (M/F: 23/30; me...

Monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic (smoldering) multiple myeloma (sMM) precede symptomatic myeloma (MM) but are characterized by significant heterogeneity in terms of biological characteristics and clinical course. Currently no single molecular or clinical feature can identify patients (pts) who should be tre...

Introduction The preferred upfront treatment of transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM) consists of the combination of lenalidomide and dexamethasone (Rd) with a third antimyeloma agent of a different mechanism of action (e.g., proteasome inhibitors or anti-CD38 monoclonal antibodies). Belantamab mafod...

Introduction Circulating tumor cells (CTCs) have been proposed as a prognostic biomarker in newly-diagnosed MM (NDMM) but their low frequency questions their use in clinical practice. Lower CTC levels (cut-off <0.01-0.07%) correlate with a favorable prognostic outcomes in transplant-eligible (TE) patients (pts); however, several issues remain to be...

Introduction: Asymptomatic monoclonal gammopathies (MGUS, SMM or aWM) are common among adults >50y. Peripheral neuropathy (PN) refers to any disorder of the peripheral nervous system including mononeuropathies, and symmetrical or asymmetrical polyneuropathy. PN is also common among individuals >50y. Common risk factors include diabetes, vitamin def...

AL amyloidosis is a clonal disease, characterized by the production of light chains from a usually small or modest in size plasma or B-cell clone. Early mortality due to severe organ involvement is the most ominous complication, long term sequalae, associated with organ involvement resulting in end stage dysfunction occurs but other long-term compl...

Introduction Waldenstrom macroglobulinemia (WM) is a rare, indolent non-Hodgkin lymphoplasmacytic lymphoma of the bone marrow (BM), characterized by monoclonal IgM protein production. WM is preceded by IgM monoclonal gammopathy of undetermined significance (IgM MGUS) and smoldering WM (SWM), which are clinically detectable but asymptomatic precurso...

The therapeutic targeting of tumor cells with loss of function (LOF) for tumor suppressor genes (TSGs) is challenging across cancers, including hematologic neoplasias, because pharmacological mechanisms to restore the function(s) of such genes are not readily feasible, in contrast to e.g., inhibition of oncogenic drivers. We reasoned, however, that...

Bortezomib-based triplets have been the mainstay of primary therapy for patients with newly diagnosed symptomatic myeloma (NDMM) for more than a decade. Bortezomib with dexamethasone and cyclophosphamide (VCD or CyBorD) has been a very popular regimen with significant activity and favorable toxicity profile, especially for patients with renal dysfu...

Introduction: SystemicAL amyloidosis is a progressive and often fatal disease caused by misfolded light chains that aggregate into amyloid fibrils and deposit in vital organs, leading to organ dysfunction. Current standard of care (SoC) therapies for AL amyloidosis target the plasma cell clone to reduce or eliminate light chain production, but do n...

Despite the notable progress that has been achieved in the realm of MM treatment, the persistence of elevated relapse rates and therapy resistance remain a substantial hindrance to effective management of the patients. Therefore, the development of modern tools to ameliorate patients' prognosis and predict treatment outcome is of first clinical pri...

Background Sporadic cardiac transthyretin amyloidosis (wtATTR) is a degenerative age-related disease with dismal prognosis and continuously increasing incidence. ATTR may have adverse effects also on vascular function and accelerate vascular aging. Tafamidis, a new agent that stabilizes the TTR tetramer improves wtATTR prognosis; however, whether t...

Background Light chain amyloidosis (AL) is a plasma cell dyscrasia in which cardiac involvement determines the prognosis. Cardiotoxicity of light chains (LCs) complicates the management of heart failure in AL and has not been addressed in the clinical praxis. We have previously genetically identified and biotechnologically produced full-length LCs...