59 results on '"I. Vaxman"'
Search Results
2. 'Real-life' data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma—the Mayo Clinic experience
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I. Vaxman, J. Abeykoon, A. Dispenzieri, S. K. Kumar, F. Buadi, M. Q. Lacy, D. Dingli, Y. Hwa, A. Fonder, M. Hobbs, C. Reeder, T. Sher, S. Hayman, T. Kourelis, R. Warsame, E. Muchtar, N. Leung, R. Go, W. Gonsalves, M. Siddiqui, R. A. Kyle, S. V. Rajkumar, McCullough Kristen, P. Kapoor, and M. A. Gertz
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Belantamab mafodotin is a highly selective targeted therapy for multiple myeloma. It targets the B cell maturation antigen (BCMA) on plasma cells and showed promising results in several randomized clinical trials. We report the outcomes of 36 patients treated at Mayo Clinic. Our cohort received a median of eight prior lines of therapy. Six patients received belantamab in combination with other medications (pomalidomide, cyclophosphamide, thalidomide), 13 patients (36%) were 70 years or older, two patients had a creatinine of >2.5 mg/dL, and one patient was on dialysis. All three patients with renal failure received full dose belantamab. Chimeric antigen receptor (CAR-T) therapy was used prior to belantamab in seven patients and none of them responded to belantamab therapy. The overall response rate (ORR) was 33% (CR 6%, VGPR 8%, PR 19%), like the ORR reported in the DREAMM-2 trial. Keratopathy developed in 16 patients (43%), grade 1 in six patients, grade 2 in seven patients, and grade 3 in three patients. Eight percent discontinued therapy due to keratopathy. The median PFS and OS was 2 months and 6.5 months, respectively.
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- 2021
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3. P966: DARATUMUMAB, CARFILZOMIB, POMALIDOMIDE AND ELOTUZUMAB FOR THE TREATMENT OF POEMS SYNDROME- THE MAYO CLINIC EXPERIENCE
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I. Vaxman, S. Kumar, F. buadi, M. Lacy, D. Dingli, A. Fonder, M. Hobbs, S. Hayman, L. Y. hwa, T. Kouralis, R. Warsame, E. Muchtar, L. Nelson, P. Kapoor, M. Grogan, R. Go, W. Gonsalves, M. Siddiqi, K. Robert, V. Rajkumar, M. Gertz, and A. Dispenzieri
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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4. PS1399 REAL WORLD DATA ON THE EFFICACY AND SAFETY OF DARATUMUMAB FOR TREATMENT OF PATIENTS WITH RELAPSED/REFRACTORY AL AMYLOIDOSIS: A MULTI-SITE RETROSPECTIVE STUDY
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N. Lavie, S. Levi, M. Gatt, I. Avivi, I. Vaxman, T. Shragai, T. Tadmor, M. Zektser, Y.C. Cohen, and O. Rouvio
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Pediatrics ,medicine.medical_specialty ,business.industry ,Relapsed refractory ,medicine ,Multi site ,AL amyloidosis ,Daratumumab ,Retrospective cohort study ,Hematology ,business ,medicine.disease ,Real world data - Published
- 2019
5. P6160Anthracycline cardiotoxicity in patients with acute myeloid leukemia: cardiovascular risk assessment, monitoring and management
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I. Vaxman, Oren Pasvolsky, M Vaturi, Ran Kornowski, P. Raanani, Zaza Iakobishvili, O Morelli, and I. Amitai
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Oncology ,Cardiotoxicity ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,Myeloid leukemia ,In patient ,Cardiology and Cardiovascular Medicine ,business ,Risk assessment - Published
- 2017
6. Role of Autologous Transplant in Newly Diagnosed Multiple Myeloma Patients Treated with Novel Triplets: A Systematic Review and Meta-Analysis.
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Amitai I, Gurion R, Raanani P, Vaxman I, Yeshurun M, Magen H, Gafter-Gvili A, and Shargian L
- Abstract
Introduction: High-dose therapy with melphalan followed by autologous stem cell transplant at the upfront setting (upfront ASCT) has significantly improved clinical outcomes of myeloma patients and become the standard of care for the past 30 years. However, with the advent of modern induction therapy, the role of upfront ASCT approach has been called into question. Several prospective studies have examined whether continuing with triplet therapy as consolidation with optional ASCT at relapse (triplet-alone) could result in comparable outcomes., Methods: This was a systematic review and meta-analysis of randomized controlled trials comparing upfront ASCT vs. triplet-alone approach among myeloma patients treated with triplet therapy as induction. Cochrane Library, PubMed, conference proceedings and references were searched until January 2023. Primary outcome was overall survival (OS). Secondary outcomes included progression free survival (PFS), safety, and SPM. Subgroup analysis was conducted for high risk cytogenetics (defined by the presence of either 17p deletion, t(4;14) or t(14;16))., Results: Our search yielded three trials, conducted between 2010-2018, including 1,737 patients. Two trials evaluated bortezomib plus lenalidomide (VRd) induction and the third study tested carfilzomib plus lenalidomide (KRd) induction. Maintenance was given in all trials to both arms. There was no difference in OS between the arms, the pooled OS in all patients and in those with high-risk cytogenetics was HR 1.03 (95% CI, 0.85-1.26; I2 = 0%; 1,737 patients, 3 trials), and 0.85 (95% CI, 0.59-1.23; I2=0%; 222 patients, 2 trials), respectively. The pooled PFS for upfront ASCT vs. triplet-alone was significantly improved in all the patients and in the high-risk cytogenetics subgroup, HR 0.67 [95% CI 0.59-0.76; I2 = 0%; 1,737 patients, 3 trials] and HR 0.59 [95% CI 0.44-0.7; I2 = 0%; 306 patients, 3 trials], respectively. The risk of any grade 3-4 adverse events was higher in the upfront ASCT arm vs triplet-alone approach [RR=1.17 [95% CI, 1.12-1.23; 1,737 patients]. The risk of secondary malignancies was reported in all three trials and was comparable between both arms. Two trials reported on secondary myeloid neoplasms, which were significantly higher among upfront ASCT arm vs triplet-alone approach, OR 9.7 (1.8-52.25, I2=0%, 1422 patients)., Conclusion: Although upfront ASCT approach in the era of triplet therapy resulted in significantly longer PFS among all patients, this did not translate into a survival benefit, regardless of cytogenetics risk. Upfront ASCT arm was associated with an increase rate of secondary myeloid neoplasms. In the current plethora of innovative therapies, the role of upfront ASCT is debatable., (S. Karger AG, Basel.)
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- 2024
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7. Correction: Outcomes among newly diagnosed AL amyloidosis patients with a very high NT-proBNP: implications for trial design.
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Vaxman I, Kumar SK, Buadi F, Lacy MQ, Dingli D, Hwa Y, Fonder A, Hobbs M, Hayman S, Kourelis T, Warsame R, Muchtar E, Leung N, Kapoor P, Grogan M, Go R, Lin Y, Gonsalves W, Siddiqui M, Kyle RA, Rajkumar SV, Gertz MA, and Dispenzieri A
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- 2024
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8. Lymphoplasmacytic lymphoma and multiple myeloma coexisting in the same patient: a case series and literature review.
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Itchaki G, Jarhovsky O, Castillo JJ, Hassan H, Gatt ML, Leiba M, Raanani P, Gertz MA, and Vaxman I
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- Humans, Male, Aged, Middle Aged, Female, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Aged, 80 and over, Multiple Myeloma complications, Multiple Myeloma diagnosis, Multiple Myeloma therapy, Waldenstrom Macroglobulinemia complications, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia therapy
- Abstract
The simultaneous occurrence of Waldenström macroglobulinemia and multiple myeloma in the same patient has been published as case reports. Patients with Waldenström macroglobulinemia often have a small clone of plasma cells. However, the concurrent occurrence of symptomatic myeloma with lytic bone lesions is rare. The diagnosis of this 'hybrid' entity is challenging, and there are no standard therapies. We present six patients from five centers (three in Israel and two in the United States). We describe these patients' unique clinical course and treatment approaches.
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- 2024
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9. Historical Perspective of High-Dose Therapy Followed by Autologous Stem Cell Transplantation in Multiple Myeloma.
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Cohen I, Vaxman I, and Gertz MA
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Background: High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) has become part of standard of care (SOC) in newly diagnosed multiple myeloma. In this review, we provide a historical perspective on ASCT since its introduction in the 1990s., Summary: Overall survival (OS) benefit for HDT followed by ASCT was demonstrated in studies comparing HDT with ASCT to standard-dose therapy (SDT) before the era of novel agents. Conditioning is done with melphalan 200 mg/m2. Lower doses (MEL140, MEL150) for older patients with comorbidities are safe and have comparable results. The addition of busulfan to melphalan improves progression-free survival (PFS) but not OS. HDT with ASCT after induction with novel agents prolongs PFS but not OS compared to SDT alone. The benefit is more evident in patients with high-risk cytogenetics. Mobilization can be achieved with granulocyte colony-stimulating factor alone, but is improved with the addition of chemotherapy. Plerixafor reduces mobilization failure and enables sufficient stem cell collection after induction with novel agents. ASCT is safe with a low rate of mortality (1%), and selected patients can be managed as outpatients., Key Messages: HDT followed by ASCT remains part of SOC due to its PFS benefit and relatively low toxicity., (© 2024 S. Karger AG, Basel.)
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- 2024
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10. Immune Therapies in AL Amyloidosis-A Glimpse to the Future.
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Haran A, Vaxman I, Gatt ME, and Lebel E
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Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in target organs, leading to multi-organ dysfunction. Treatment approaches have historically mirrored but lagged behind those of multiple myeloma (MM). Recent advancements in MM immunotherapy are gradually being evaluated and adopted in AL amyloidosis. This review explores the current state of immunotherapeutic strategies in AL amyloidosis, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapy. We discuss the unique challenges and prospects of these therapies in AL amyloidosis, including the exposure of frail AL amyloidosis patients to immune-mediated toxicities such as cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS), as well as their efficacy in promoting rapid and deep hematologic responses. Furthermore, we highlight the need for international initiatives and compassionate programs to provide access to these promising therapies and address critical unmet needs in AL amyloidosis management. Finally, we discuss future directions, including optimizing treatment sequencing and mitigating toxicities, to improve outcomes for AL amyloidosis patients.
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- 2024
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11. Smouldering multiple myeloma: To seek or not to seek? To treat or not to treat. That is the question.
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Vaxman I and Gatt ME
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- Humans, Disease Progression, Multiple Myeloma diagnosis, Multiple Myeloma therapy, Monoclonal Gammopathy of Undetermined Significance diagnosis, Smoldering Multiple Myeloma therapy
- Abstract
In this issue, the British Society for Haematology presents guidelines for the diagnosis and management of patients with smouldering multiple myeloma (SMM). The authors provide a practical, evidence-based approach to managing these patients. Key questions remain yet unsolved. Commentary on: Hughes et al. Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024;204:1193-1206., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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12. Microvascular cardiac amyloidosis-Cardiac involvement of amyloidosis presenting as typical chest pain.
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Vaxman I, Kaufman C, Lerman A, and Gertz MA
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- Humans, Diagnosis, Differential, Chest Pain etiology, Heart, Angina Pectoris etiology, Angina Pectoris diagnosis, Amyloidosis complications, Amyloidosis diagnosis
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Coronary microvascular angina from cardiac amyloidosis., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
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- 2023
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13. Delivery of Therapeutic RNA to the Bone Marrow in Multiple Myeloma Using CD38-Targeted Lipid Nanoparticles.
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Tarab-Ravski D, Hazan-Halevy I, Goldsmith M, Stotsky-Oterin L, Breier D, Naidu GS, Aitha A, Diesendruck Y, Ng BD, Barsheshet H, Berger T, Vaxman I, Raanani P, and Peer D
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- Humans, Animals, Mice, Bone Marrow, Neoplasm Recurrence, Local, RNA, Small Interfering therapeutic use, Multiple Myeloma drug therapy
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Multiple myeloma (MM) is a cancer of differentiated plasma cells that occurs in the bone marrow (BM). Despite the recent advancements in drug development, most patients with MM eventually relapse and the disease remains incurable. RNA therapy delivered via lipid nanoparticles (LNPs) has the potential to be a promising cancer treatment, however, its clinical implementation is limited due to inefficient delivery to non-hepatic tissues. Here, targeted (t)LNPs designed for delivery of RNA payload to MM cells are presented. The tLNPs consist of a novel ionizable lipid and are coated with an anti-CD38 antibody (αCD38-tLNPs). To explore their therapeutic potential, it is demonstrated that LNPs encapsulating small interference RNA (siRNA) against cytoskeleton-associated protein 5 (CKAP5) lead to a ≈90% decrease in cell viability of MM cells in vitro. Next, a new xenograft MM mouse model is employed, which clinically resembles the human disease and demonstrates efficient homing of MM cells to the BM. Specific delivery of αCD38-tLNPs to BM-residing and disseminated MM cells and the improvement in therapeutic outcome of MM-bearing mice treated with αCD38-tLNPs-siRNA-CKAP5 are shown. These results underscore the potential of RNA therapeutics for treatment of MM and the importance of developing effective targeted delivery systems and reliable preclinical models., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
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- 2023
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14. The short and long-term characteristics and outcomes of patients with grade 1 myocardial uptake on cardiac scintigraphy.
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Itzhaki Ben Zadok O, Ruhrman-Sahar N, Mats I, Vaxman I, Shiyovich A, Aviv Y, Vaturi M, Wiessman M, Shochat T, Kandinov I, Kornowski R, and Hamdan A
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- Female, Humans, Retrospective Studies, Heart, Radionuclide Imaging, Myocardium, Amyloid Neuropathies, Familial diagnostic imaging
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Aims: This study aimed to characterize the final diagnosis and prognosis of patients with grade 1 myocardial scintigraphy uptake, which is an unequivocal result for the diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) requiring further invasive investigation with tissue biopsy., Methods and Results: We retrospectively compared the clinical and imaging parameters of patients suspected for ATTR-CA (based on clinical and echocardiographic parameters) with grade 1 vs. grades 2/3 technetium pyrophosphate uptake on cardiac scintigraphy. Prospectively, grade 1 patients underwent re-evaluation for ATTR-CA at long term. Of the 132 ATTR-CA suspected patients, 89 (67%) were diagnosed as grade 1 and 43 (33%) as grades 2/3 uptake. Grade 1 vs. grades 2/3 patients were younger and female predominant with lower biomarker levels and left ventricular mass. Based on available imaging and pathology findings, only 6 out of the 89 patients with grade 1 uptake (7%) were finally diagnosed with light-chain cardiac amyloidosis, whereas no patient was diagnosed with ATTR-CA. At 2 [interquartile range (IQR) 0.75, 3.25] years of follow-up, the survival of patients with grade 1 vs. grades 2/3 uptake was significantly better [hazard ratio 0.271 (95% confidence interval 0.130 to 0.563, P = 0.0005)]. Prospectively, 30 patients with grade 1 uptake were re-evaluated at a median follow-up of 3.2 (IQR 2.2, 3.9) years. Their New York Heart Association class, biomarker levels, and echocardiography findings remained stable. No patient (0/25) demonstrated grades 2/3 uptake at repeated long-term scintigraphy., Conclusions: Patients with suspected ATTR-CA and a grade 1 scintigraphy uptake demonstrate a stable clinical, laboratory, imaging, and scintigraphy phenotype along with a benign survival profile at long-term follow-up. Larger studies should define the optimal evaluation strategy in this population., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
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- 2023
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15. Daratumumab, carfilzomib, and pomalidomide for the treatment of POEMS syndrome: The Mayo Clinic Experience.
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Vaxman I, Kumar SK, Buadi F, Lacy MQ, Dingli D, Hayman S, Kourelis T, Warsame R, Hwa Y, Fonder A, Hobbs M, Muchtar E, Leung N, Kapoor P, Go R, Lin Y, Gonsalves W, Siddiqui M, Kyle RA, Rajkumar SV, Gertz MA, and Dispenzieri A
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- Humans, Antineoplastic Combined Chemotherapy Protocols, Thalidomide therapeutic use, Multiple Myeloma drug therapy, POEMS Syndrome
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- 2023
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16. Venetoclax in Relapse/Refractory AL Amyloidosis-A Multicenter International Retrospective Real-World Study.
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Lebel E, Kastritis E, Palladini G, Milani P, Theodorakakou F, Aumann S, Lavi N, Shargian L, Magen H, Cohen Y, Gatt ME, and Vaxman I
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Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax. The median lines of therapy prior to venetoclax was 3.5 (range 1-7), and 88% of our cohort had t (11;14). Twenty-two patients (85%) were previously treated with daratumumab. The overall hematologic response rate was 88%, 35% achieved a CR, and 35% achieved VGPR. The median event-free survival was 25 months (m) (95% CI 9.7 m-not reached), and the median overall survival was 33 m (95% CI 25.9-39.2 m). Most of the patients in this cohort are in ongoing deep responses and continuing venetoclax therapy. The treatment was relatively safe. One patient died due to infection, and there were two grade 3 infections in our cohort. Tumor lysis syndrome (TLS) was not seen in any patient. Dose reductions were frequent but did not affect the efficacy. These promising results require confirmation in a randomized controlled trial.
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- 2023
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17. Clinical features, therapy patterns, outcomes and prognostic factors of solitary plasmacytomas: a report of the Israeli Myeloma Study Group.
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Ganzel C, Trestman S, Levi S, Gatt ME, Lavi N, Vaxman I, Rouvio O, Magen H, Lebel E, Horowitz NA, Leiba M, Tadmor T, Herzog Tzarfati K, Surio C, Yeganeh S, Dally N, Avivi I, and Cohen YC
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- Humans, Prognosis, Israel, Prospective Studies, Neoplasm Recurrence, Local, Plasmacytoma therapy, Multiple Myeloma, Bone Neoplasms therapy
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Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia. In this retrospective multicenter study, 68 SP patients were included. Compared to solitary extramedullary plasmacytoma (SEP), patients with solitary bone plasmacytoma (SBP) were younger (57.3 vs. 70.9 years, p = 0.031), had larger plasmacytoma (median: 5.4 vs. 3 cm, p = 0.007) and higher median involved free light chain level (61 vs. 25.8 mg/L, p = 0.056). 92.6% of patients were treated by radiotherapy and 11.8% received systemic anti-myeloma treatment. With a median follow-up of 42 months, 45.6% of patients progressed (8.8% - recurrent SP, 36.8% - active myeloma). The median PFS was 58 months and the median OS has not been reached (10-year OS: 84.8%). Patients who received also anti-myeloma treatment had longer PFS compared to those who did not (median not reached vs. 48 months, p = 0.056). In conclusion, SBP and SEP appear to be different diseases. Radiotherapy is the cornerstone in the SP treatment. A large prospective trial is needed to evaluate the impact of adding systemic anti-myeloma treatment to local radiotherapy.
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- 2022
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18. How I approach smoldering multiple myeloma.
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Vaxman I and Gertz MA
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- Disease Progression, Humans, Risk Factors, Multiple Myeloma drug therapy, Multiple Myeloma therapy, Smoldering Multiple Myeloma diagnosis, Smoldering Multiple Myeloma therapy
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The current standard of care in smoldering multiple myeloma (SMM) is close surveillance, outside of clinical trials. Efforts are being made to understand the pathobiologic process that leads to the progression of SMM to active MM. This review provides a critical description of available data, including risk factors and risk models of progression, as well as clinical trials investigating interventions for this patient population. We describe 2 cases in which patients were seen before the concept of a myeloma-defining event was established. Today, based on the International Myeloma Working Group criteria, both patients would have been identified as experiencing myeloma-defining events, and therapy would have been initiated. These cases show that occasionally, patients can undergo observation only, even when they exceed criteria for high-risk SMM., (© 2022 by The American Society of Hematology.)
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- 2022
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19. Clinical and pathological predictors for FDG-PET/CT avidity in patients with marginal zone lymphoma-a retrospective cohort study.
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Kagan KBT, Guz D, Buchrits S, Gurion R, Vaxman I, Priss M, Groshar D, Catalano OA, Sherban A, Raanani P, Gafter-Gvili A, and Bernstine H
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- Adult, Humans, Ki-67 Antigen, Positron Emission Tomography Computed Tomography methods, Prognosis, Retrospective Studies, Fluorodeoxyglucose F18, Lymphoma, B-Cell, Marginal Zone diagnostic imaging
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Background: The clinical value of FDG-PET/CT for staging and monitoring treatment response in patients with aggressive lymphoma is well established. Conversely, its role in the assessment and management of marginal zone lymphoma (MZL) is less conclusive. We aimed to assess clinical, laboratory, and pathological predictors for FDG uptake in these patients, in an attempt to identify MZL patients whose management will benefit from this imaging modality., Methods: In this single-center, retrospective cohort study, we included all adult patients diagnosed with MZL at the Rabin Medical Center between January 2006 and December 2020 who underwent FDG-PET/CT at the time of diagnosis. Primary outcomes were FDG avidity (defined as a visual assessment of at least moderate intensity), SUVmax, and SUVliver. Variables such as advanced clinical stage, primary disease site, hemoglobin level (Hb), platelet count (Plt), serum albumin, LDH level, β-2 microglobulin, and Ki 67 index were evaluated univariate and multivariate analysis using logistic and linear regression models. Association between FDG avidity and progression-free and overall survival was evaluated using Kaplan-Meier curves and Cox regression analysis., Results: A total of 207 MZL patients were included in this study, 76 of whom (36.7%) had FDG-avid disease. Baseline patients' characteristics such as age, gender, and comorbid conditions were similar between patients with and without significant FDG uptake. In a multivariate logistic regression model, non-gastric MALT (OR 4.2, 95% CI 1.78-10), Ki 67 index ≥ 15% (OR 3.64, 95% CI 1.36-9.76), and elevated LDH level (OR 8.6, 95% CI 3.2-22.8) were all associated with positive FDG avidity. In a multivariate linear regression model, a combination of advanced clinical stage, specific disease subtypes, LDH level, and Ki 67 index predicted the value of SUVmax (P value < 0.001; adjusted R
2 = 33.8%) and SUVmax/SUVliver (P value < 0.001; adjusted R2 = 27%). Baseline FDG avidity was associated to PFS and OS only in univariate analyses., Conclusions: In this retrospective cohort study, we present prediction models for positive FDG uptake and SUVmax in MZL patients. These models aim to help clinicians choose patients suitable for incorporation of FDG-PET/CT for staging and monitoring disease and reduce the costs of redundant tests., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2022
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20. Foot drop in patients treated with bortezomib - a case series and review of the literature.
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Vaxman I, Mauerman ML, Gatt ML, Berger T, and Gertz MA
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- Bortezomib adverse effects, Humans, Quality of Life, Antineoplastic Agents adverse effects, Multiple Myeloma complications, Multiple Myeloma drug therapy, Peripheral Nervous System Diseases chemically induced, Peripheral Nervous System Diseases diagnosis, Peroneal Neuropathies chemically induced
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Bortezomib-induced peripheral neuropathy (BIPN) has a profound impact on quality of life, which is an important issue considering the growing number of survivors of multiple myeloma and amyloidosis. BIPN is typically symmetric, distal, "stocking and glove" distribution and predominantly consists of sensory rather than motor symptoms. In this case series, we report an acute neurotoxicity syndrome induced by bortezomib, which is clinically distinct from BIPN by not being peripheral and distal. We describe six patients that developed unilateral or bilateral foot drop attributed to bortezomib. With bortezomib discontinuation symptoms improved gradually over months to years.
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- 2022
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21. Prevalence and Clinical Characteristics of Paraproteinemia Associated with Chronic Myeloid Leukemia.
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Berger T, Shacham Abulafia A, Shimony S, Pasvolsky O, Vaxman I, Miron Y, Feldman S, Leader A, and Raanani P
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- Humans, Middle Aged, Prevalence, Cross-Sectional Studies, Multiple Myeloma diagnosis, Paraproteinemias complications, Paraproteinemias epidemiology, Monoclonal Gammopathy of Undetermined Significance complications, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance epidemiology, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology
- Abstract
Introduction: Data regarding the prevalence of paraproteinemia in patients with chronic myeloid leukemia (CML) are lacking., Methods: To evaluate for the prevalence of paraproteinemia, we undertook this cross-sectional study among consecutive chronic-phase CML patients. Complete blood count, chemistry, immunoglobulins, serum-free light chains, serum-protein electrophoresis and immunofixation were collected. Further analyses evaluated whether various patient-, disease-, and treatment-related variables are associated with paraproteinemia., Results: One hundred patients, median age 63.5 (IQR 48.1-72) years were recruited. Median time from CML diagnosis to enrollment was 6.3 (IQR 2.3-11.3) years. Monoclonal protein was detected in 8 patients (8%), diagnosed with smoldering multiple myeloma (SMM, n = 2) and low-risk monoclonal gammopathy of undetermined significance (MGUS, n = 6). Six patients were on tyrosine kinase inhibitor treatment, 2 were in treatment-free remission. The only covariate associated with paraproteinemia was the presence of anemia, albeit with borderline statistical significance in univariate analysis (p = 0.053) and when adjusted for age (p = 0.056)., Conclusions: In this largest study so far describing the prevalence of paraproteinemia among CML patients, we found MGUS prevalence to be higher than the 3.2% expected prevalence in the general population above 50 years and a non-negligible prevalence of SMM (2%). Screening for paraproteinemia in CML patients, especially in the presence of anemia, should be considered., (© 2022 S. Karger AG, Basel.)
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- 2022
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22. "Real-life" data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma-the Mayo Clinic experience.
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Vaxman I, Abeykoon J, Dispenzieri A, Kumar SK, Buadi F, Lacy MQ, Dingli D, Hwa Y, Fonder A, Hobbs M, Reeder C, Sher T, Hayman S, Kourelis T, Warsame R, Muchtar E, Leung N, Go R, Gonsalves W, Siddiqui M, Kyle RA, Rajkumar SV, Kristen M, Kapoor P, and Gertz MA
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Agents, Immunological adverse effects, Female, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Multiple Myeloma drug therapy, Neoplasm Recurrence, Local drug therapy
- Abstract
Belantamab mafodotin is a highly selective targeted therapy for multiple myeloma. It targets the B cell maturation antigen (BCMA) on plasma cells and showed promising results in several randomized clinical trials. We report the outcomes of 36 patients treated at Mayo Clinic. Our cohort received a median of eight prior lines of therapy. Six patients received belantamab in combination with other medications (pomalidomide, cyclophosphamide, thalidomide), 13 patients (36%) were 70 years or older, two patients had a creatinine of >2.5 mg/dL, and one patient was on dialysis. All three patients with renal failure received full dose belantamab. Chimeric antigen receptor (CAR-T) therapy was used prior to belantamab in seven patients and none of them responded to belantamab therapy. The overall response rate (ORR) was 33% (CR 6%, VGPR 8%, PR 19%), like the ORR reported in the DREAMM-2 trial. Keratopathy developed in 16 patients (43%), grade 1 in six patients, grade 2 in seven patients, and grade 3 in three patients. Eight percent discontinued therapy due to keratopathy. The median PFS and OS was 2 months and 6.5 months, respectively., (© 2021. The Author(s).)
- Published
- 2021
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23. Outcomes among newly diagnosed AL amyloidosis patients with a very high NT-proBNP: implications for trial design.
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Vaxman I, Kumar SK, Buadi F, Lacy MQ, Dingli D, Hwa Y, Fonder A, Hobbs M, Hayman S, Kourelis T, Warsame R, Muchtar E, Leung N, Kapoor P, Grogan M, Go R, Lin Y, Gonsalves W, Siddiqui M, Kyle RA, Rajkumar SV, Gertz MA, and Dispenzieri A
- Subjects
- Clinical Trials as Topic, Humans, Immunoglobulin Light-chain Amyloidosis metabolism, Immunoglobulin Light-chain Amyloidosis pathology, Prognosis, Retrospective Studies, Survival Rate, Biomarkers blood, Immunoglobulin Light-chain Amyloidosis blood, Natriuretic Peptide, Brain blood, Peptide Fragments blood, Troponin T blood
- Published
- 2021
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24. Should high risk smoldering myeloma be treated outside a clinical trial: NO.
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Gertz MA and Vaxman I
- Subjects
- Disease Progression, Humans, Risk Factors, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Smoldering Multiple Myeloma
- Published
- 2021
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25. The Efficacy and Safety of Chemotherapy-Based Stem Cell Mobilization in Multiple Myeloma Patients Who Are Poor Responders to Induction: The Mayo Clinic Experience.
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Vaxman I, Muchtar E, Jacob E, Kapoor P, Kumar S, Dispenzieri A, Buadi F, Dingli D, Gonsalves W, Kourelis T, Warsame R, Lacy M, Hogan W, and Gertz MA
- Subjects
- Hematopoietic Stem Cell Mobilization, Humans, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Heterocyclic Compounds adverse effects, Multiple Myeloma drug therapy
- Abstract
We report the outcomes of 117 patients with newly diagnosed multiple myeloma who received novel agent induction, had a poor response to induction, and were mobilized using intravenous intermediate-dose cyclophosphamide (82%) or VD-PACE (18%) plus granulocyte colony-stimulating factor (G-CSF) and on-demand plerixafor. The median progression-free survival and overall survival of the chemo-mobilized cohort were 21 months (95% confidence interval [CI], 15-71) and 58 months (95% CI, 47-80), respectively. We compared our cohort to a 117-patient cohort matched by the level of response at pretransplant evaluation. The matched patients were mobilized with G-CSF and on-demand plerixafor without chemotherapy. Patients receiving chemo-mobilization had higher stem cell yields than the growth-factor-only cohort (median, 10.7 × 10
6 cells/kg vs. 8.77 × 106 cells/kg, respectively; P < .001). The safety profile of chemo-mobilization was favorable, and there was no difference between the two groups in length of hospitalization during autologous stem cell transplantation (P = .95), days to neutrophil engraftment (P = .22), days to platelet engraftment (P = .27), or risk of bacteremia (P = .52). Twenty-nine percent of the chemo-mobilized cohort and 65% of the matched cohort required plerixafor for adequate mobilization (P < .001). Chemo-mobilization enhances stem cell collection without adversely impacting the post-transplant clinical course., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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26. The Role of Autologous Stem Cell Transplantation in Amyloidosis.
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Vaxman I and Dispenzieri A
- Subjects
- Disease-Free Survival, Hematopoietic Stem Cell Transplantation methods, Humans, Immunoglobulin Light-chain Amyloidosis mortality, Transplantation Conditioning methods, Immunoglobulin Light-chain Amyloidosis therapy, Stem Cell Transplantation methods, Transplantation, Autologous methods
- Abstract
Autologous stem cell transplantation (ASCT) has been an essential part of the treatment armamentarium in light chain (AL) amyloidosis for several decades. Patients who achieve a complete hematologic response following ASCT have a long overall survival. However, only 1 randomized controlled trial compared ASCT with the standard of care used at the time, which was melphalan and dexamethasone, and the results did not support the use of ASCT in AL amyloidosis. These results are of limited significance due to the unexpected high transplant-related mortality (TRM) (24%). TRM is a major concern in AL amyloidosis, but its incidence can be lessened by better patient selection and by patients receiving ASCT in specialized centers. ASCT in AL amyloidosis is performed only in selected patients; approximately 20% of patients with AL amyloidosis are transplant eligible up front or after bortezomib (Velcade) based conditioning. The introduction of newer agents such as bortezomib and daratumumab (Darzalex), which lead to deep responses and have good safety profiles, encourage revisiting the benefit and timing of ASCT in the modern era. This review provides a comprehensive assessment of eligibility criteria for ASCT in AL amyloidosis, conditioning dosing, efficacy in terms of hematologic and organ response, and future areas of research.
- Published
- 2021
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27. Differences in the characteristics and contemporary cardiac outcomes of patients with light-chain versus transthyretin cardiac amyloidosis.
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Itzhaki Ben Zadok O, Vaturi M, Vaxman I, Iakobishvili Z, Rhurman-Shahar N, Kornowski R, and Hamdan A
- Subjects
- Aged, Aged, 80 and over, Cardiomyopathies etiology, Cardiomyopathies pathology, Echocardiography, Female, Follow-Up Studies, Heart Failure etiology, Heart Failure pathology, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Rate, Ventricular Function, Left, Amyloid Neuropathies, Familial complications, Cardiomyopathies mortality, Heart Failure mortality, Immunoglobulin Light-chain Amyloidosis complications
- Abstract
Aims: To compare the baseline cardiovascular characteristics of immunoglobulin light-chain (AL) and amyloid transthyretin (ATTR) cardiac amyloidosis (CA) and to investigate patients' contemporary cardiac outcomes., Methods: Single-center analysis of clinical, laboratory, echocardiographic and cardiac magnetic resonance imaging (CMRi) characteristics of AL and ATTR-CA patients' cohort (years 2013-2020)., Results: Included were 67 CA patients of whom 31 (46%) had AL-CA and 36 (54%) had ATTR-CA. Patients with ATTR-CA versus AL-CA were older (80 (IQR 70, 85) years versus 65 (IQR 60, 71) years, respectively, p<0.001) with male predominance (p = 0.038). Co-morbidities in ATTR-CA patients more frequently included diabetes mellitus (19% versus 3.0%, respectively, p = 0.060) and coronary artery disease (39% versus 10%, respectively, p = 0.010). By echocardiography, patients with ATTR-CA versus AL-CA had a trend to worse left ventricular (LV) ejection function (50 (IQR 40, 55)% versus 60 (IQR 45, 60)%, respectively, p = 0.051), yet comparable LV diastolic function. By CMRi, left atrial area (31 (IQR 27, 36)cm2 vs. 27 (IQR 23, 30)cm2, respectively, p = 0.015) and LV mass index (109 (IQR 96, 130)grams/m2 vs. 82 (IQR 72, 98)grams/m2, respectively, p = 0.011) were increased in patients with ATTR-CA versus AL-CA. Nevertheless, during follow-up (median 20 (IQR 10, 38) months), patients with AL-CA were more frequently admitted with heart failure exacerbations (HR 2.87 (95% CI 1.42, 5.81), p = 0.003) and demonstrated increased mortality (HR 2.51 (95%CI 1.19, 5.28), p = 0.015)., Conclusion: Despite the various similarities of AL-CA and ATTR-CA, these diseases have distinct baseline cardiovascular profiles and different heart failure course, thus merit tailored-cardiac management., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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28. Measurable residual disease in multiple myeloma and light chain amyloidosis: more than meets the eye.
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Vaxman I and Gertz MA
- Subjects
- Humans, Neoplasm Recurrence, Local, Neoplasm, Residual, Treatment Outcome, Immunoglobulin Light-chain Amyloidosis diagnosis, Immunoglobulin Light-chain Amyloidosis therapy, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Abstract
The emergence of highly effective multiple myeloma (MM) treatments may bring cure within reach and highlights the need for highly sensitive measurable residual disease (MRD) techniques to replace conventional response assessments. MRD is being incorporated as an endpoint in an increasing number of studies and had been repeatedly shown to be both a predictive marker of response to treatment and a prognostic marker for future relapse. However, those results should be cautiously interpreted due to non-uniform reporting and the need for longer follow up to assess for sustained MRD negativity. This review aims to critically analyze the key MRD aspects including the current evidence supporting the use of MRD in clinical practice and the pitfalls of the various methods used to assess MRD. The utility of MRD for light chain (AL) amyloidosis will also be discussed.
- Published
- 2021
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29. Autologous stem cell transplantation for multiple myeloma patients aged ≥ 75 treated with novel agents.
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Vaxman I, Visram A, Kumar S, Dispenzieri A, Buadi F, Dingli D, Lacy M, Muchtar E, Kapoor P, Hogan W, Hayman S, Leung N, Gonsalves W, Kourelis T, Warsame R, Berger T, and Gertz MA
- Subjects
- Disease-Free Survival, Humans, Melphalan, Stem Cell Transplantation, Transplantation Conditioning, Transplantation, Autologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy
- Abstract
Autologous stem cell transplantation (ASCT) has been used for treating multiple myeloma (MM) for over three decades and is generally reserved for patients younger than 65. Herein we report on outcomes of outpatient ASCT in a cohort of patients with MM aged ≥75 years. Between October 2005 and August 2020, 50 patients aged ≥75 years, received an ASCT at Mayo Clinic, Rochester. Median time from diagnosis to ASCT was 6.85 months (IQR 5.2-10.52) and 50%. received reduced intensity conditioning with melphalan 140 mg/m
2 . 48% of patients completed the ASCT without requiring hospitalization and 52% (n = 26) of patients required hospitalization with a median duration of hospital admission of 9 days (IQR 5-13). Reasons for hospitalization included fever or infection (32%), cardiac arrhythmia (36%), and dehydration (32%). Overall response rate was 100% with a complete response seen in 57% of patients. Median overall survival and progression free survival for the cohort were 82 months and 33 months, respectively. One patient died within 100 days of transplant representing a 2% 100-day mortality rate. ASCT is safe and efficacious in carefully selected MM patients aged 75 or above and we believe that age should not be an exclusion factor for ASCT in MM.- Published
- 2021
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30. Disease monitoring with quantitative serum IgA levels provides a more reliable response assessment in multiple myeloma patients.
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Visram A, Vaxman I, S Al Saleh A, Parmar H, Dispenzieri A, Kapoor P, Lacy MQ, Gertz MA, Buadi FK, Hayman SR, Dingli D, Warsame R, Kourelis T, Siddiqui M, Gonsalves W, Muchtar E, Lust JA, Leung N, Kyle RA, Murray D, Rajkumar SV, and Kumar S
- Subjects
- Aged, Disease Progression, Female, Humans, Immunoglobulin A metabolism, Male, Middle Aged, Monitoring, Physiologic methods, Multiple Myeloma metabolism, Myeloma Proteins metabolism, Progression-Free Survival, Retrospective Studies, Immunoglobulin A blood, Multiple Myeloma blood
- Abstract
Unlike IgG monoclonal proteins (MCPs), IgA MCP quantification is unreliable due to beta-migration of IgA MCPs on serum protein electrophoresis (SPEP). The utility of nephelometric quantitative IgA (qIgA) to monitor IgA multiple myeloma (MM) is unclear. We retrospectively studied disease response kinetics using qIgA versus MCPs by SPEP, and developed and validated novel qIgA disease assessment criteria in 491 IgA MM patients. The SPEP MCP nadir occurred a median of 41 (IQR 0-102) days before the qIgA. The median time to achieve a partial response (PR) was shorter using standard IMWG versus qIgA response criteria (32 vs 58 days, p < 0.001). Stratification by qIgA criteria, unlike IMWG criteria, led to clear separation of the progression-free survival curves of patients achieving a PR or very good PR. There was a consistent trend toward earlier detection of disease progression using qIgA versus IMWG progression criteria. In conclusion, monitoring IgA MM using MCP-based IMWG criteria may be falsely reassuring, given that MCP levels on SPEP decrease faster than qIgA levels. The qIgA response criteria more accurately stratify patients based on the progression risk and may detect disease progression earlier, which may lead to more consistent measurement of trial endpoints and improved patient outcomes.
- Published
- 2021
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31. Depth of response prior to autologous stem cell transplantation predicts survival in light chain amyloidosis.
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Vaxman I, Sidiqi MH, Al Saleh AS, Kumar S, Muchtar E, Dispenzieri A, Buadi F, Dingli D, Lacy M, Hayman S, Leung N, Gonsalves W, Kourelis T, Warsame R, Hogan W, and Gertz M
- Subjects
- Humans, Melphalan, Retrospective Studies, Stem Cell Transplantation, Transplantation, Autologous, Treatment Outcome, Amyloidosis therapy, Hematopoietic Stem Cell Transplantation, Immunoglobulin Light-chain Amyloidosis therapy
- Abstract
The goal of therapy in AL amyloidosis is to inhibit further production of the amyloidogenic light chains, thereby allowing organ recovery and improving survival. We aimed to assess the impact of depth of hematologic response prior to ASCT on survival. We conducted a retrospective study of 128 newly diagnosed AL amyloidosis patients who received induction prior to ASCT between January 2007 and August 2017 at Mayo Clinic. The overall response rate to induction was 86% (CR 18%, VGPR 31% and PR 38%). With a median follow up of 52 months, the median PFS and OS was 48.5 months and not reached, respectively. Response depth to induction therapy was associated with improved PFS and OS. The median PFS was not reached for patients achieving ≥VGPR prior to ASCT and 34.1 months for patients achieving PR or less (P = 0.0009). The median OS was longer in patients with deeper responses (not reached for ≥VGPR vs. 128 months for PR or less (P = 0.02)). On multivariable analysis, independent predictors of OS were melphalan conditioning dose (RR = 0.42; P = 0.036) and depth of response prior to transplant (RR 0.37; P = 0.0295). Hematologic response prior to transplant predicts improved post transplant outcomes in AL amyloidosis.
- Published
- 2021
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32. Identification of resistance pathways and therapeutic targets in relapsed multiple myeloma patients through single-cell sequencing.
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Cohen YC, Zada M, Wang SY, Bornstein C, David E, Moshe A, Li B, Shlomi-Loubaton S, Gatt ME, Gur C, Lavi N, Ganzel C, Luttwak E, Chubar E, Rouvio O, Vaxman I, Pasvolsky O, Ballan M, Tadmor T, Nemets A, Jarchowcky-Dolberg O, Shvetz O, Laiba M, Shpilberg O, Dally N, Avivi I, Weiner A, and Amit I
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal administration & dosage, Case-Control Studies, Dexamethasone administration & dosage, Drug Resistance, Neoplasm, Female, Humans, Lenalidomide administration & dosage, Male, Middle Aged, Neoplasm Recurrence, Local, Oligopeptides administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy, Multiple Myeloma pathology, Single-Cell Analysis methods
- Abstract
Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR-Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors.
- Published
- 2021
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33. Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review.
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Shragai T, Gatt M, Lavie N, Vaxman I, Tadmor T, Rouvio O, Zektser M, Horowitz N, Magen H, Ballan M, Suru C, Luttwak E, Levi S, Ziv-Baran T, Avivi I, and Cohen YC
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Biomarkers, Clinical Trials as Topic, Disease Management, Female, Humans, Immunoglobulin Light-chain Amyloidosis diagnosis, Immunoglobulin Light-chain Amyloidosis etiology, Immunoglobulin Light-chain Amyloidosis mortality, Male, Middle Aged, Prognosis, Recurrence, Retrospective Studies, Sensitivity and Specificity, Severity of Illness Index, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Immunoglobulin Light-chain Amyloidosis drug therapy
- Abstract
Objectives: Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting., Methods: A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations., Results: Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was ≥ 3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04-0.81; P = .03) in a multi-variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression-free survival (PFS) was 28.4 months and median overall survival (OS) was not reached; 2-year PFS and OS were 68.6 ± 7.5% and 90.4 ± 4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n = 517) and 2 clinical trials (n = 62) meeting prespecified criteria., Conclusions: Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2021
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34. Retroperitoneal involvement with light chain amyloidosis- case series and literature review.
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Vaxman I, Visram A, Pasvolsky O, Kumar S, Dispenzieri A, Buadi F, Dingli D, Lacy M, Hayman S, Kyle R, Kapoor P, Leung N, Gonsalves W, Kourelis T, Warsame R, and Gertz M
- Subjects
- Humans, Israel, Prognosis, Amyloidosis diagnosis, Amyloidosis therapy, Immunoglobulin Light-chain Amyloidosis complications, Immunoglobulin Light-chain Amyloidosis diagnosis, Immunoglobulin Light-chain Amyloidosis therapy
- Abstract
Retroperitoneal involvement is rare in patients with light chain (AL) amyloidosis and has only been published as case reports. Only 5 cases of retroperitoneal deposition have previously been reported in the setting of systemic AL amyloidosis. Data regarding the characteristics and clinical course of these patients are scarce. Herein we report on eleven patients with systemic AL amyloidosis diagnosed with retroperitoneal deposition at all three Mayo Clinic sites and Davidoff cancer center in Israel. All patients had retroperitoneal amyloid deposition at presentation. All patients received systemic treatment. Eight patients presented with hydronephrosis and 7 had nephrostomy tubes or stents inserted. Regression of the deposition was documented in one patient and one patient was able to have his nephrostomy tube removed. The median OS from diagnosis was 150 months, suggesting that retroperitoneal deposition might confer improved prognosis compared to the general amyloid population.
- Published
- 2021
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35. Characteristics and outcome of multiple myeloma patients presenting with anaemia only: A retrospective multi-centre study.
- Author
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Shragai T, Gatt ME, Shaulov A, Katodritou E, Triantafyllou T, Lavi N, Pouli A, Sioni A, Vaxman I, Zektser M, Ganzel C, Benyamini N, Trestman S, Ziv-Baran T, Adam Y, Cohen YC, and Avivi I
- Subjects
- Adult, Aged, Aged, 80 and over, Autografts, Bortezomib adverse effects, Female, Humans, Male, Middle Aged, Retrospective Studies, Anemia mortality, Anemia therapy, Bortezomib administration & dosage, Hematopoietic Stem Cell Transplantation, Multiple Myeloma mortality, Multiple Myeloma therapy
- Abstract
Background: Multiple myeloma (MM) patients presenting with anaemia as their sole clinical manifestation are rare and not fully defined., Methods: Retrospective multi-site study comparing the characteristics and outcome of MM patients with anaemia only with matched patients, presenting with multi-organ disease., Results: Anaemia-only patients had a higher percentage of bone marrow monoclonal plasma cells group (median 60% [IQR 42-80%] vs. 37% [IQR 17-65%], respectively; p < 0.001), and a lower responsiveness to treatment (≥VGPR rates were 54% vs 74%, p = 0.049). Median survival in anaemia only patients was 65.9 ± 6.9 vs 83.4 ± 8.8 months in matched control patients (P = n.s)., Conclusions: MM patients presenting with anaemia only represents a unique, potentially less favorable population., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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36. Outcomes of multiple myeloma patients with del 17p undergoing autologous stem cell transplantation.
- Author
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Vaxman I, Visram A, Kapoor P, Kumar S, Dispenzieri A, Buadi F, Dingli D, Muchtar E, Gonsalves W, Rajkumar V, Kourelis T, Warsame R, Lacy M, and Gertz MA
- Subjects
- Adult, Aged, Autografts, Chromosomes, Human, Pair 17, Disease-Free Survival, Female, Humans, Male, Middle Aged, Survival Rate, Chromosome Deletion, Hematopoietic Stem Cell Transplantation, Multiple Myeloma genetics, Multiple Myeloma mortality, Multiple Myeloma therapy, Smith-Magenis Syndrome
- Published
- 2021
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- View/download PDF
37. Prognostic value of NT-ProBNP and troponin T in patients with light chain amyloidosis and kidney dysfunction undergoing autologous stem cell transplantation.
- Author
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Al Saleh AS, Parmar HV, Vaxman I, Visram A, Hasib Sidiqi M, Muchtar E, Buadi FK, Dispenzieri A, Warsame R, Lacy MQ, Dingli D, Gonsalves WI, Wolf RC, Kourelis TV, Hogan WJ, Hayman SR, Kapoor P, Kumar SK, and Gertz MA
- Subjects
- Biomarkers, Humans, Kidney, Natriuretic Peptide, Brain, Peptide Fragments, Prognosis, Transplantation, Autologous, Troponin T, Amyloidosis, Hematopoietic Stem Cell Transplantation
- Published
- 2021
- Full Text
- View/download PDF
38. Acute Liver Rejection in a Multiple Myeloma Patient Treated with Lenalidomide.
- Author
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Vaxman I, Eaton J, Lee HE, and Gertz MA
- Abstract
Herein we present a patient that underwent a liver transplant due to primary biliary cholangitis (PBC) and after 9 years developed multiple myeloma. Following the cessation of mycophenolate mofetil and 2 weeks after lenalidomide treatment was started, the patient experienced acute cellular rejection. The patient recovered after treatment with corticosteroids, resumption of mycophenolate mofetil, and cessation of lenalidomide. Lenalidomide-associated allograft rejection has been reported in other organs. However, this is the first case report of liver rejection induced by lenalidomide., Competing Interests: Dr. Gertz reports personal fees from Ionis/Akcea, personal fees from Alnylam, personal fees from Prothena, personal fees from Janssen, grants and personal fees from Spectrum, personal fees from Annexon, personal fees from Appellis, personal fees from Amgen, personal fees from Medscape, personal fees from Physicians Education Resource, personal fees for Data Safety Monitoring board from Abbvie and Celgene, personal fees from Research to Practice, workforce training Sanofi, speaker fees from Teva, speaker fees from Johnson and Johnson, speaker fees from Medscape, and speaker fees from DAVA oncology; Advisory Board for Pharmacyclics Advisory Board for Proclara; Development of educational materials for i3Health.Royalties from Springer Publishing, Stock Options Aurora Bio., (Copyright © 2020 Iuliana Vaxman et al.)
- Published
- 2020
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39. Correlation between urine ACR and 24-h proteinuria in a real-world cohort of systemic AL amyloidosis patients.
- Author
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Visram A, Al Saleh AS, Parmar H, McDonald JS, Lieske JC, Vaxman I, Muchtar E, Hobbs M, Fonder A, Hwa YL, Buadi FK, Dingli D, Lacy MQ, Dispenzieri A, Kapoor P, Hayman SR, Warsame R, Kourelis TV, Siddiqui M, Gonsalves WI, Lust JA, Kyle RA, Vincent Rajkumar S, Gertz MA, Kumar SK, and Leung N
- Subjects
- Aged, Albuminuria therapy, Female, Humans, Immunoglobulin Light-chain Amyloidosis therapy, Male, Middle Aged, Retrospective Studies, Albuminuria urine, Immunoglobulin Light-chain Amyloidosis urine
- Abstract
A 24-h urine protein collection (24hUP), the gold standard for measuring albuminuria in systemic AL amyloidosis, is cumbersome and inaccurate. We retrospectively reviewed 575 patients with systemic AL amyloidosis to assess the correlation between a urine albumin to creatinine ratio (uACR) and the 24hUP. The uACR correlated strongly with 24hUP at diagnosis (Pearson's r = 0.87, 95% CI 0.83-0.90) and during the disease course (Pearson's r = 0.88, 95% CI 0.86-0.90). A uACR ≥300 mg/g estimated a 24hUP ≥ 500 mg with a sensitivity of 92% and specificity of 97% (area under the receiver operating curve = 0.938, 95% CI 0.919-0.957). A uACR cutoff of 3600 mg/g best predicted a 24hUP > 5000 g (sensitivity 93%, specificity 94%), and renal stage at diagnosis was strongly concordant using either 24hUP or uACR as the proteinuria measure (k = 0.823, 95% CI 0.728-0.919). In patients with serial urine collections, a > 30% decrease in uACR predicted a > 30% decrease in 24hUP with a sensitivity of 94%. In conclusion, the uACR is a reliable and convenient method for ruling out proteinuria >500 mg per day, prognosticating renal outcomes, and assessing renal response to therapy. Further studies are needed to validate the uACR cutoffs proposed in this study.
- Published
- 2020
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40. Colon perforation in multiple myeloma patients - A complication of high-dose steroid treatment.
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Vaxman I, Al Saleh AS, Kumar S, Nitin M, Dispenzieri A, Buadi F, Dingli D, Lacy M, Muchtar E, Hobbs M, Fonder A, Hwa L, Visram A, Kapoor P, Siddiqui M, Lust J, Kyle R, Rajkumar V, Hayman S, Leung N, Gonsalves W, Kourelis T, Warsame R, and Gertz MA
- Subjects
- Adult, Aged, Aged, 80 and over, Colonic Diseases diagnostic imaging, Colonic Diseases surgery, Colostomy, Dexamethasone administration & dosage, Diverticulitis, Colonic complications, Female, Humans, Intestinal Perforation diagnostic imaging, Intestinal Perforation surgery, Male, Middle Aged, Retrospective Studies, Risk Assessment, Risk Factors, Steroids administration & dosage, Tomography, X-Ray Computed, Treatment Outcome, United States, Colonic Diseases chemically induced, Dexamethasone adverse effects, Intestinal Perforation chemically induced, Multiple Myeloma drug therapy, Steroids adverse effects
- Abstract
Gastrointestinal complications of multiple myeloma (MM) treatment are common and include nausea, constipation, and diarrhea. However, acute gastrointestinal events like perforations are rare. We aimed to describe the characteristics and outcomes of patients with MM that had colonic perforations during their treatment. This is a retrospective study that included patients from all three Mayo Clinic sites who had MM and developed a colonic perforation. All patients were diagnosed with colonic perforations based on CT scans and were surgically treated. Patients diagnosed with AL amyloidosis, a perforated colon complicating neutropenic colitis during ASCT and those with perforation due to colonic cancer were excluded. A high dose of dexamethasone was defined as ≥40 mg dexamethasone once a week. Thirty patients met inclusion criteria. All patients received steroids at doses ≥10 mg once weekly prior to the perforation, while four (11%) were on high-dose dexamethasone without chemotherapy. Fourteen patients were given high doses of dexamethasone. Twenty-five patients required ostomies with all surviving surgery. Twenty-four perforations (80%) were associated with diverticulitis. Treatment with steroids was resumed in 23 patients with no further gastrointestinal complications. The median OS was 20 months following perforation (IQR 8-59). Within the same timeframe 5854 patients were treated at Mayo Clinic for MM, making the risk of bowel perforation 0.5%. Intestinal perforations in MM are rare and, in our series, always occurred with dexamethasone ≥10 mg per week. Urgent surgery is lifesaving and resumption of anti-myeloma treatment appears to be safe., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2020
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41. Prior Carpal Tunnel Syndrome and Early Concomitant Echocardiographic Findings Among Patients With Cardiac Amyloidosis.
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Itzhaki Ben Zadok O, Abelow A, Vaxman I, Eisen A, Iakobishvili Z, Sagie A, Kornowski R, and Vaturi M
- Subjects
- Echocardiography, Humans, Prealbumin, Amyloidosis diagnosis, Amyloidosis diagnostic imaging, Carpal Tunnel Syndrome diagnostic imaging, Carpal Tunnel Syndrome epidemiology, Heart Failure
- Abstract
Background: We aimed to characterize patients with systemic amyloidosis stratified by a prior diagnosis of carpal tunnel syndrome (CTS) and to describe early echocardiographic parameters concomitant with CTS., Methods and Results: Patients with suspected amyloidosis during CTS diagnosis were excluded. Our cohort included 108 patients with systemic amyloidosis of which 36% had a prior CTS at a median of 4 years (interquartile range [IQR] 2.8-6.7 years) before disease diagnosis. Patients with prior CTS were more likely to present subsequently with cardiac amyloidosis (78% vs 53%, P = .013), yet overall survival was comparable between groups (53% vs 61%, P = .825). Prior CTS was more commonly diagnosed in subsequent patients with transthyretin (62%) than in patients with immunoglobulin light chain (24%, P < .001). Furthermore, in a subanalysis of patients subsequently diagnosed with cardiac amyloidosis, findings at CTS diagnosis (n = 17) demonstrated a mild increase in septal thickness 1.3 cm (IQR 1.2-1.5 cm), increased relative wall thickness 0.46 cm (IQR 0.45-0.58 cm), and increased left ventricular mass index 155 g/m
2 (IQR 92-177 g/m2 ) compared with age-adjusted normal range echocardiographic values. Doppler mitral flow data was supportive of left ventricular diastolic dysfunction., Conclusions: Early echocardiographic findings at CTS diagnosis, preceding the diagnosis of cardiac amyloidosis by several years, are suggestive of increased wall thickness and diastolic dysfunction., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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42. Waldenstrom's macroglobulinemia in the era of immunotherapy.
- Author
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Vaxman I and Gertz M
- Subjects
- Humans, Immunoglobulin M, Immunologic Factors, Immunotherapy, Rituximab, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia drug therapy
- Abstract
Waldenstrom macroglobulinemia (WM) is a lymphoplasmacytic lymphoma that presents with symptomatic anemia, thrombocytopenia, constitutional symptoms, extramedullary disease and rarely hyperviscosity syndrome. The presence of both IgM monoclonal protein and ≥10% monoclonal lymphoplasmacytic cells is required for the diagnosis. MyD88 is present in 67-90% of patients but is not pathognomonic for WM. Many patients who fulfill the criteria of WM are asymptomatic and do not require treatment. Recent advances in the understanding of the biology of WM have paved the way for new treatment options. The use of novel agents with or without rituximab enables the use of effective chemotherapy-free regiments upfront and in the relapsed setting. New targeted treatments such as venetoclax and CXCR4 antagonists are being investigated.
- Published
- 2020
- Full Text
- View/download PDF
43. New developments in diagnosis, risk assessment and management in systemic amyloidosis.
- Author
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Vaxman I, Dispenzieri A, Muchtar E, and Gertz M
- Subjects
- Humans, Risk Assessment, Immunoglobulin Light Chains metabolism, Immunoglobulin Light-chain Amyloidosis diagnosis, Immunoglobulin Light-chain Amyloidosis drug therapy, Immunoglobulin Light-chain Amyloidosis metabolism, Immunoglobulin Light-chain Amyloidosis pathology, Plasma Cells metabolism, Plasma Cells pathology
- Abstract
Amyloidosis is a group of disorders characterized by a misfolded protein that deposits in organs and compromise their function. Clinician should have a high index of suspicion because in most cases, the clinical picture is non-specific. Typing of amyloid is of utmost importance and should be an integral part of accurately diagnosing a patient. AL amyloidosis is the most common systemic amyloidosis in the western world in which the misfolded proteins are immunoglobulin light chains secreted by clonal plasma cells. New data about prognostication of AL amyloidosis patients are accumulating. The treatment goal is to eradicate the amyloidogenic plasma cell clone, by using high dose melphalan and/or novel agents (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies against CD38). Early diagnosis is important for effectively treating the patient as late diagnosis hampers chances for organ recovery. ATTR amyloidosis is less recognized but is increasingly seen due to better recognition and improved diagnostic tools. New data about treatment options (patisiran, inotersen and tafamidis) have recently been published and are discussed., Competing Interests: Declaration of competing interest # Dr. Gertz reports personal fees from Ionis/Akcea, personal fees from Alnylam, personal fees from Prothena, personal fees from Celgene, personal fees from Janssen, grants and personal fees from Spectrum, personal fees from Annexon, personal fees from Appellis, personal fees from Amgen, personal fees from Medscape, personal fees from Physicians Education Resource, personal fees for Data Safety Monitoring board from Abbvie, personal fees from Research to Practice, speaker fees from Teva, Speaker fees from Johnson and Johnson; Speaker fees from Medscape, Speaker fees DAVA oncology; Advisory Board for Pharmacyclics Advisory Board for Proclara outside the submitted work; Development of educational materials for i3Health. Educational Program development i3Health. Royalties from Springer Publishing. Grant Funding Amyloidosis Foundation; International Waldenstrom's Macroglobulinemia Foundation. NCI SPORE MM SPORE 5P50 CA186781-04. # Dr Angela Dispenzieri - Research dollars from Alnylam, Prothena, Celgene, Takeda, Janssen, and Pfizer. # Dr Eli Muchtar - Nothing to declare. # Dr Iuliana Vaxman - Advisory Board for Celgene; Advisory Board for Takeda; Advisory Board for Promedicao; Speaker fees from Takeda., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
44. Non-transplant eligible multiple myeloma: deciphering optimal first line regimens.
- Author
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Vaxman I and Gertz M
- Subjects
- Antineoplastic Combined Chemotherapy Protocols, Bortezomib, Humans, Melphalan, Prednisone, Hematopoietic Stem Cell Transplantation, Multiple Myeloma
- Published
- 2020
- Full Text
- View/download PDF
45. When to Suspect a Diagnosis of Amyloidosis.
- Author
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Vaxman I and Gertz M
- Subjects
- Amyloidosis etiology, Amyloidosis metabolism, Amyloidosis therapy, Animals, Diagnosis, Differential, Disease Susceptibility, Humans, Immunoglobulin Light-chain Amyloidosis diagnosis, Immunoglobulin Light-chain Amyloidosis etiology, Immunoglobulin Light-chain Amyloidosis metabolism, Immunoglobulin Light-chain Amyloidosis therapy, Male, Middle Aged, Organ Specificity, Phenotype, Amyloidosis diagnosis
- Abstract
Amyloidosis is a group of complex diseases caused by extracellular deposition of pathological insoluble fibrillary protein in organs and tissues and may result in severe organ dysfunction. Despite the etiological heterogeneity of systemic amyloidosis, the clinical manifestations of the different forms of amyloidosis largely overlap and depend upon the effected organ. The signs and symptoms that should raise suspicion for the potential diagnosis of amyloidosis are usually nonspecific; therefore, establishing the diagnosis is difficult, and early diagnosis requires clinical suspicion. Light chain (AL) amyloidosis may present with highly specific signs such as macroglossia and periorbital purpura, but these signs are insensitive. Amyloidosis is still underdiagnosed, even though treatments are now available and are effective in improving patient's survival and quality of life. Cardiac amyloidosis is the major determinant of survival, and the earlier it is detected the better the survival. All MGUS patients should be routinely screened for AL amyloidosis by a focused history and physical examination and routine assessment of urine albumin. The aim of this review is to provide clinicians with knowledge about the signs and symptoms that raise the suspicion of amyloidosis, bearing in mind the importance of early diagnosis of this disease., (© 2020 S. Karger AG, Basel.)
- Published
- 2020
- Full Text
- View/download PDF
46. Worldwide Perspectives of Amyloidosis.
- Author
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Vaxman I and Gertz MA
- Subjects
- Amyloidosis etiology, Disease Management, Humans, Treatment Outcome, Amyloidosis diagnosis, Amyloidosis therapy
- Published
- 2020
- Full Text
- View/download PDF
47. Anthracycline-Induced Cardiotoxicity in Acute Myeloid Leukemia Patients Who Undergo Allogeneic Hematopoietic Stem Cell Transplantation.
- Author
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Pasvolsky O, Morelli O, Rozovski U, Vaturi M, Wolach O, Amitai I, Vaxman I, Ratzon R, Yeshurun M, Kornowski R, Iakobishvilli Z, and Raanani P
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cardiotoxicity diagnosis, Daunorubicin administration & dosage, Echocardiography, Female, Heart Function Tests, Humans, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Transplantation, Homologous, Young Adult, Anthracyclines adverse effects, Cardiotoxicity etiology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute therapy
- Abstract
Introduction: There is paucity of data regarding the cardiotoxic effects of anthracycline treatment in the context of acute myeloid leukemia (AML) patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT). Even a transient decrease in cardiac function might affect transplantation outcome., Patients and Methods: We reviewed the clinical records and echocardiography examinations of 78 patients with AML who received induction therapy and underwent HSCT., Results: Twenty-two patients (28%) received daunorubicin at a dose of 90 mg/m
2 per day and 53 patients (68%) received 60 mg/m2 per day or an equivalent dose of idarubicin. In 14 patients (18%) the postinduction ejection fraction declined by at least 10%. This change was temporary in 6 patients and longstanding in the remainder. Patients who developed systolic dysfunction had inferior overall survival (13 months compared with 27 months; P = .013). Patients whose diastolic function deteriorated had improved survival outcome (38 months compared with 17 months; P = .048)., Conclusion: Although even transient reduction in systolic function might compromise survival outcome, diastolic dysfunction predicts improved survival in patients with AML who undergo HSCT., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
48. Hemophagocytic lymphohistiocytosis as a harbinger of aggressive lymphoma: a case series.
- Author
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Pasvolsky O, Zoref-Lorenz A, Abadi U, Geiger KR, Hayman L, Vaxman I, Raanani P, and Leader A
- Subjects
- Aged, Aged, 80 and over, Humans, Male, Middle Aged, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic pathology, Lymphohistiocytosis, Hemophagocytic therapy, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large-Cell, Anaplastic diagnosis, Lymphoma, Large-Cell, Anaplastic pathology, Lymphoma, Large-Cell, Anaplastic therapy
- Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome, which can manifest either secondary to a variety of underlying causes, or due to a primary genetic defect. Malignancy is the most common underlying disease in adults with HLH, with lymphomas being the most common malignancy. Lymphoma-associated hemophagocytic syndrome (LAHS) typically follows a rapidly progressive clinical course and is associated with poor prognosis. We herein present four patients with HLH associated with aggressive lymphoma. At initial presentation, the underlying etiology of the HLH was unclear. Two patients were eventually diagnosed with anaplastic large cell lymphoma, while the other two had diffuse large B cell lymphoma. Two of the patients experienced rapid clinical deterioration, one at diagnosis and the other at relapse, and both died prior to diagnosis of lymphoma despite HLH-directed therapy. These cases highlight the need for intensive management in adults with HLH without a clear etiology, especially in cases when lymphoma-associated HLH is suspected. We describe the current pitfalls in diagnosis and treatment of LAHS and discuss possible ways to improve patient management.
- Published
- 2019
- Full Text
- View/download PDF
49. FDG PET/CT as a diagnostic and prognostic tool for the evaluation of marginal zone lymphoma.
- Author
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Vaxman I, Bernstine H, Kleinstern G, Hendin N, Shimony S, Domachevsky L, Gurion R, Groshar D, Raanani P, and Gafter-Gvili A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Glucose-6-Phosphate administration & dosage, Humans, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Survival Rate, Glucose-6-Phosphate analogs & derivatives, Helicobacter Infections diagnostic imaging, Helicobacter Infections mortality, Helicobacter Infections therapy, Helicobacter pylori, Lymphoma, B-Cell, Marginal Zone diagnostic imaging, Lymphoma, B-Cell, Marginal Zone mortality, Lymphoma, B-Cell, Marginal Zone therapy, Positron-Emission Tomography
- Abstract
We evaluated the role of 18-fluoro-2-deoxy-d-glucose positron emission tomography (
[18F] FDG-PET) with computed tomography (CT) (PET/CT) as a diagnostic and prognostic tool in newly diagnosed marginal zone lymphoma (MZL) patients. This is a retrospective cohort study of patients with newly diagnosed MZL, treated with immunotherapy, chemotherapy regimens, surgery, or Helicobacter pylori eradication between 2008 and 2016 in a single tertiary center. Only patients who had a pretreatment PET/CT (P-PET/CT) were included. P-PET/CT, interim (I-PET/CT), and end-of-treatment PET/CT (E-PET/CT) studies were reviewed. P-PET/CT results were reported using two methods of evaluation, qualitative and semi quantitative: visual assessment (VAS) and maximal standardized uptake value (SUVmax), and I-PET and E-PET results were reported by Deauville 5-point score (DS) evaluation as well. Avidity of PET/CT was defined as abnormal uptake in any of these methods. The primary outcome was the prognostic role of P-PET/CT, I-PET/CT, and E-PET/CT on progression-free survival (PFS) and overall survival (OS). Data of 196 patients with MZL were identified, 110 of which had P-PET/CT and were included in this analysis. Median age was 67 years (range 18-93). The median follow-up period was 63 months (range 3-278). The median OS and PFS for the whole cohort were 63 (interquartile range 39-85) and 60 (interquartile range 37-76) months, respectively. The avidity of PET at baseline for the whole cohort was 70% (77/110 patients), for MALT lymphoma, 62.5% (40/64 patients), for NMZL, 76.4% (13/17 patients), and for SMZL, 82.7% (24/29 patients). When adjusted for IPI, sex, and comorbidities, positive E-PET/CT was associated with reduced PFS with a hazard ratio (HR) of 3.4 (95% CI, 1.27-9.14, P = 0.02). Positive E-PET/CT did not correlate with OS. However, there were only three events. P-PET/CT was not predictive of PFS or OS. Our study demonstrates that above 70% of MZL are FDG avid. Positive E-PET/CT is a strong prognostic factor for PFS., (© 2019 John Wiley & Sons, Ltd.)- Published
- 2019
- Full Text
- View/download PDF
50. Risk adapted post-transplant maintenance in multiple myeloma.
- Author
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Vaxman I and Gertz M
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Maintenance Chemotherapy methods, Transplantation, Autologous, Antineoplastic Agents therapeutic use, Bortezomib therapeutic use, Hematopoietic Stem Cell Transplantation methods, Lenalidomide therapeutic use, Multiple Myeloma therapy, Thalidomide therapeutic use
- Abstract
Introduction: The survival of multiple myeloma patients is increasing due to new medications, the widespread implementation of autologous stem cell transplantation and better supportive treatments. The controversy surrounding post-transplant treatment is debated due to a lack of large randomized trials comparing the different treatment modalities. The questions for each proposed treatment are whether it improves outcomes, has low cumulative toxicities and is easy to administer. Areas covered: In this review, we have summarized the current data on maintenance therapy in newly diagnosed MM patients undergoing ASCT, focusing on bortezomib, thalidomide and lenalidomide as well as newer agents Expert opinion: Maintenance treatment has been shown to deepen and prolong responses and increase PFS and OS. Lenalidomide is approved for maintenance and guidelines recommend its use post ASCT. Ixazomib has recently been reported to improve PFS.
- Published
- 2019
- Full Text
- View/download PDF
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