Review
Oncology
Jonathan A. Webster, Leo Luznik, Ivana Gojo
Summary: Advances in allo-HCT have shifted the primary cause of treatment failure for AML patients from transplant-related mortality to disease relapse. Post-transplant relapsed AML presents a clinical challenge due to transplant-related toxicities increasing the risk of treatment-related morbidity and mortality.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Misha C. Tran, Yasmin Hasan, Amy Wang, Kamil Yenice, Julien Partouche, Wendy Stock, Richard A. Larson, Satyajit Kosuri, James L. LaBelle, Justin Kline, Peter A. Riedell, Andrew S. Artz, Ralph Weichselbaum, Michael R. Bishop, Bulent Aydogan, Hongtao Liu
Summary: Relapse after allo-SCT is a common issue, and a second SCT can be considered for treatment. The study explored the feasibility of combining IM-TMI with fludarabine and melphalan for conditioning in patients undergoing a second or greater allo-SCT. The results showed that the combination therapy was feasible and achieved favorable outcomes.
Article
Hematology
Stephane de Botton, Pierre Fenaux, Karen Yee, Christian Recher, Andrew H. Wei, Pau Montesinos, David C. Taussig, Arnaud Pigneux, Thorsten Braun, Antonio Curti, Carolyn Grove, Brian A. Jonas, Asim Khwaja, Ollivier Legrand, Pierre Peterlin, Montserrat Arnan, William Blum, Daniela Cilloni, Devendra K. Hiwase, Joseph G. Jurcic, Juergen Krauter, Xavier Thomas, Justin M. Watts, Jay Yang, Olga Polyanskaya, Julie Brevard, Jennifer Sweeney, Emma Barrett, Jorge Cortes
Summary: Olutasidenib (FT-2102) is an effective and selective oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). In a pivotal cohort study, olutasidenib monotherapy showed a complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 35% and an overall response rate of 48% in IDH1 inhibitor-naive patients with mIDH1R132 relapsed/refractory acute myeloid leukemia (AML). The median duration of CR/CRh was 25.9 months, and the median overall survival was 11.6 months. Grade 3 or 4 adverse events included febrile neutropenia, anemia, thrombocytopenia, and neutropenia. Differentiation syndrome adverse events occurred in 14% of patients, with one fatal case reported. Olutasidenib provides a therapeutic advance in this poor-prognostic population of AML patients with mIDH1 R/R. This trial was registered at www.clinicaltrials.gov as #NCT02719574.
Article
Hematology
Maximilian Stahl, Kamal Menghrajani, Andriy Derkach, Alexander Chan, Wenbin Xiao, Jacob Glass, Amber C. King, Anthony F. Daniyan, Christopher Famulare, Bernadette M. Cuello, Troy Z. Horvat, Omar Abdel-Wahab, Ross L. Levine, Aaron D. Viny, Eytan M. Stein, Sheng F. Cai, Mikhail Roshal, Martin S. Tallman, Aaron D. Goldberg
Summary: Combination therapy of venetoclax is effective in many patients with relapsed or refractory AML, with azacitidine+venetoclax showing higher response rates compared to low-dose cytarabine+venetoclax. Clinical and molecular characteristics of patients may predict treatment outcomes in this population.
Review
Oncology
Patrick K. Reville, Tapan M. Kadia
Summary: Despite advancements in AML treatment, high rates of relapse remain a clinical challenge even in patients achieving complete remission. Maintenance therapy options like hypomethylating agents show promise in improving outcomes, with ongoing research continuing to clarify their true role in AML treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Livius Penter, Satyen H. Gohil, Teddy Huang, Emily M. Thrash, Dominik Schmidt, Shuqiang Li, Mariano Severgnini, Donna Neuberg, F. Stephen Hodi, Kenneth J. Livak, Robert Zeiser, Pavan Bachireddy, Catherine J. Wu
Summary: Relapse of myeloproliferative neoplasms (MPNs) post-allogeneic hematopoietic stem cell transplantation (HSCT) is challenging, with limited efficacy in reinstating graft-versus-leukemia (GVL) responses. PD-1 blockade therapy with nivolumab has shown clinical activity in relapsed MPN patients, leading to transient expansion of CD4+ T cells and contraction of AML subpopulations with megakaryocytic features and high PD-L1 expression. Single-cell technologies can provide valuable insight into the cellular mechanisms underlying response to PD-1 blockade in relapsed myeloid diseases for future therapeutic developments.
Article
Oncology
Hua Jin, Yu Zhang, Sijian Yu, Xin Du, Na Xu, Ruoyang Shao, Dongjun Lin, Yanqiu Chen, Jie Xiao, Zhiqiang Sun, Lan Deng, Xinquan Liang, Hongyu Zhang, Ziwen Guo, Min Dai, Pengcheng Shi, Fen Huang, Zhiping Fan, Zhao Yin, Li Xuan, Ren Lin, Xuejie Jiang, Guopan Yu, Qifa Liu
Summary: This study investigated the efficacy and tolerability of the venetoclax combined with azacitidine plus homoharringtonine (VAH) regimen in patients with relapsed or refractory acute myeloid leukemia (R/R AML). The results showed that VAH regimen has promising therapeutic efficacy and tolerability in R/R AML, with high overall response rate and encouraging survival.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Oncology
Jubin Zhang, Lijuan Qi, Tanzhen Wang, Jingnan An, Biqi Zhou, Yanglan Fang, Yujie Liu, Meng Shan, Dengli Hong, Depei Wu, Yang Xu, Tianhui Liu
Summary: The study identified the role of Fifth Ewing Variant (FEV) in regulating the homing and expansion of acute myeloid leukemia (AML) cells. FEV was found to be re-expressed in relapsed AML samples and interference of FEV expression delayed leukemic progression. FEV was also found to activate integrin subunit alpha 4 (ITGA4) transcription, and inhibition of ITGA4 reduced the migration and colony-forming abilities of AML cells.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Maria Chiara Barbanti, Niamh Appleby, Murali Kesavan, Toby Andrew Eyre
Summary: Cellular therapy, such as allogenic stem cell transplantation and chimeric antigen receptor T-cell therapy, continues to be explored in high-risk chronic lymphocytic leukemia and Richter syndrome. However, these treatment modalities have limitations and specific placement in treatment algorithms.
FRONTIERS IN ONCOLOGY
(2022)
Editorial Material
Hematology
Roni Shouval, Robert J. Soiffer
Summary: The study in this issue of Blood explores the potential use of a knowledge bank to guide decision making on whether AML patients aged 18 to 59 should undergo allogeneic HSCT in first complete remission or at a later stage.
Article
Oncology
Xiwen Tong, Mengyuan Li, Jie Jin, Yi Li, Li Li, Yizhou Peng, Lifang Huang, Bin Xu, Fankai Meng, Xia Mao, Liang Huang, Wei Huang, Donghua Zhang
Summary: This study aimed to analyze the risk factors associated with relapse post allo-HSCT in R/R AML and high-risk MDS patients and evaluate the efficacy of a new conditioning regimen containing decitabine and cladribine. The results showed that CR before allo-HSCT and matched sibling donors were independent protective factors for survival, while DNMT3A abnormality was an independent risk factor for both relapse and no-relapse survival. The new conditioning regimen demonstrated a low relapse rate, high survival rate, and no increased incidence of GVHD or adverse effects, suggesting its potential use in allo-HSCT for R/R AML and high-risk MDS.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Shigeki Hirabayashi, Ryuji Uozumi, Tadakazu Kondo, Yasuyuki Arai, Takahito Kawata, Naoyuki Uchida, Atsushi Marumo, Kazuhiro Ikegame, Takahiro Fukuda, Tetsuya Eto, Masatsugu Tanaka, Atsushi Wake, Junya Kanda, Takafumi Kimura, Ken Tabuchi, Tatsuo Ichinohe, Yoshiko Atsuta, Masamitsu Yanada, Shingo Yano
Summary: This study aimed to develop and validate nomograms and a web application to predict the overall survival of patients with non-complete remission AML undergoing allo-HCT. Significant prognostic factors among patients undergoing allo-HCT included age, performance status, percentage of peripheral blasts, cytogenetic risk, chemotherapy response, and number of transplantations. The effectiveness of multi-drug conditioning regimens in patients undergoing CBT was indicated in the study.
Article
Oncology
Fabio Giglio, Edoardo Campodonico, Francesca Lorentino, Maddalena Noviello, Elisabetta Xue, Raffaella Greco, Lorenzo Lazzari, Alessandro Bruno, Maria Teresa Lupo Stanghellini, Matteo Giovanni Carrabba, Roberta La Starza, Monica Casucci, Chiara Bonini, Sabina Chiaretti, Jacopo Peccatori, Robin Foa, Fabio Ciceri
Summary: Philadelphia-like acute lymphoblastic leukemia (ALL), a subtype with poor prognosis, requires investigation in identifying mutations for targeted treatment with tyrosine kinase-inhibitors (TKIs). This study presents a unique case of using compassionate-use ponatinib and low-dose prednisone to bridge to chimeric antigen receptor T (CAR-T) cell therapy in a relapsed/refractory Ph-like ALL patient. Maintenance therapy with low-dose ponatinib was continued and achieved measurable residual disease negativity and B-cell aplasia 20 months later. This is the first reported case of using ponatinib as a bridge and maintenance therapy after CAR-T cell therapy in Ph-like ALL.
FRONTIERS IN ONCOLOGY
(2023)
Article
Hematology
Naval G. Daver, Monique Dail, Jacqueline S. Garcia, Brian A. Jonas, Karen W. L. Yee, Kevin R. Kelly, Norbert Vey, Sarit Assouline, Gail J. Roboz, Stefania Paolini, Daniel A. Pollyea, Agostino Tafuri, Joseph M. Brandwein, Arnaud Pigneux, Bayard L. Powell, Pierre Fenaux, Rebecca L. Olin, Giuseppe Visani, Giovanni Martinelli, Maika Onishi, Jue Wang, Weize Huang, Cherie Green, Marion G. Ott, Wan-Jen Hong, Marina Y. Konopleva, Michael Andreeff
Summary: This phase 1b trial evaluated the use of venetoclax-idasanutlin in patients with relapsed/refractory acute myeloid leukemia ineligible for cytotoxic chemotherapy. The trial showed that venetoclax-idasanutlin is a feasible and effective treatment option for these patients, with manageable safety profile.
Article
Hematology
Ghayas C. Issa, Aram Bidikian, Sangeetha Venugopal, Marina Konopleva, Courtney D. DiNardo, Tapan M. Kadia, Gautam Borthakur, Elias Jabbour, Naveen Pemmaraju, Musa Yilmaz, Nicholas J. Short, Abhishek Maiti, Koji Sasaki, Lucia Masarova, Sherry Pierce, Koichi Takahashi, Guilin Tang, Sanam Loghavi, Keyur Patel, Michael Andreeff, Kapil Bhalla, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver
Summary: Mutations in Nucleophosmin 1 (NPM1) have a minimal impact on prognosis in relapsed or refractory acute myeloid leukemia (AML). However, the addition of venetoclax to salvage regimens can improve outcomes in patients with NPM1 mutations.
Article
Oncology
Rajiv Agarwal, Paul Shin, Andrea Knezevic, Judith E. Nelson, Danielle R. Romano, Camila Bernal, Anjali Desai, Andrew S. Epstein
Summary: This study assessed the accuracy of cure expectations in gastrointestinal cancer patients and found that inaccurate expectations were prevalent across all stages of the disease, particularly in those with metastatic or unresectable cancer. The accuracy was lower in advanced stages and higher in early-stage patients who received adjuvant chemotherapy. Hospitalization and location of death also had an impact on accuracy.
Review
Transplantation
Panagiotis Georgianos, Georgios Tziatzios, Stefanos Roumeliotis, Vasilios Vaios, Vasiliki Sgourogoulou, Dimitrios G. Tsalikakis, Vassilios Liakopoulos, Rajiv Agarwal
Summary: This meta-analysis study found that the use of ACEIs/ARBs is not associated with a significantly lower risk of cardiovascular events and all-cause mortality among patients on dialysis when compared with placebo or no add-on treatment.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Review
Urology & Nephrology
Rajiv Agarwal, James Burton, Maurizio Gallieni, Kamyar Kalantar-Zadeh, Gert Mayer, Carol Pollock, Jacek C. Szepietowski
Summary: Despite the limited increase in life expectancy for patients with end-stage kidney disease after the breakthrough of kidney replacement therapy, the quality of life and relief of symptoms have become increasingly important to patients. Currently, most dialysis-associated symptoms and adverse effects do not have approved treatments, and the few available treatments may add further adverse effects. This article demonstrates how understanding the pathophysiology of a particular symptom (chronic kidney disease-associated pruritus) in dialysis led to the development and regulatory approval of a treatment for that symptom. This approach can be applied to other dialysis-associated symptoms, improving the remaining years of patients' lives.
CLINICAL KIDNEY JOURNAL
(2023)
Article
Urology & Nephrology
Rajiv Agarwal, Bertram Pitt, Biff F. Palmer, Csaba P. Kovesdy, Ellen Burgess, Gerasimos Filippatos, Jolanta Malyszko, Luis M. Ruilope, Patrick Rossignol, Peter Rossing, Roberto Pecoits-Filho, Stefan D. Anker, Amer Joseph, Robert Lawatscheck, Daniel Wilson, Martin Gebel, George L. Bakris
Summary: This study compared the differences in blood pressure reduction and hyperkalemia risk between nonsteroidal MRA finerenone and steroidal MRA spironolactone +/- a potassium binder in patients with treatment-resistant hypertension and chronic kidney disease. The results showed that finerenone had a lower reduction in blood pressure and lower risk of hyperkalemia and treatment discontinuation compared to spironolactone with or without patiromer.
CLINICAL KIDNEY JOURNAL
(2023)
Review
Peripheral Vascular Disease
Panagiotis Georgianos, Rajiv Agarwal
Summary: Steroidal mineralocorticoid-receptor-antagonists (MRAs) have limited use in high-risk patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) due to the associated risk of hyperkalemia and hormonal side effects. Finerenone, a novel nonsteroidal MRA, has shown promising results in reducing cardiovascular and kidney failure outcomes in T2DM patients with a broad spectrum of CKD. Further research is underway to investigate the potential benefits of combining finerenone with a sodium-glucose co-transporter type 2 (SGLT-2) inhibitor.
AMERICAN JOURNAL OF HYPERTENSION
(2023)
Article
Hematology
Andrew J. Shih, Tomi Jun, Andrew D. Skol, Riyue Bao, Lei Huang, Sapana Vora, Megan E. McNerney, Eric A. Hungate, Michelle M. Le Beau, Richard A. Larson, Aaron Elliott, Hsiao-Mei Lu, Robert Huether, Felicia Hernandez, Friedrich Stolzel, James M. Allan, Kenan Onel
Summary: Some patients with therapy-related myeloid neoplasms (t-MN) may have unsuspected inherited cancer predisposition syndrome (CPS). A set of clinical criteria has been proposed to identify t-MN patients with high risk of CPS (HR-CPS). Among the identified HR-CPS patients, 37% had pathogenic or likely pathogenic variants, compared to 0% in the low-risk CPS patients. These simple clinical criteria help identify t-MN patients most likely to benefit from genetic testing for inherited CPS.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Endocrinology & Metabolism
Janet B. B. McGill, Rajiv Agarwal, Stefan D. D. Anker, George L. L. Bakris, Gerasimos Filippatos, Bertram Pitt, Luis M. M. Ruilope, Andreas L. L. Birkenfeld, Maria L. L. Caramori, Meike Brinker, Amer Joseph, Andrea Lage, Robert Lawatscheck, Charlie Scott, Peter Rossing, FIDELIO-DKD Investigator, FIGARO-DKD Investigator
Summary: The aim of this study was to evaluate the effect of finerenone on cardiorenal outcomes and diabetes progression, and to assess its interaction with baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use. The results showed consistent risk reductions in cardiovascular and kidney outcomes with finerenone compared to placebo across subgroups. Higher HbA1c variability was associated with an increased risk of cardiorenal outcomes. The study concludes that finerenone is effective regardless of baseline characteristics. Overall, the study is rated 9 out of 10.
DIABETES OBESITY & METABOLISM
(2023)
Article
Oncology
Jorge E. Cortes, Andreas Hochhaus, Naoto Takahashi, Richard A. Larson, Ghayas C. Issa, Felice Bombaci, Nicholas Ramscar, Sophie Ifrah, Timothy P. Hughes
Summary: Asciminib, a BCR-ABL1 inhibitor that works through the STAMP mechanism, has shown favorable efficacy and safety in patients with chronic myeloid leukemia in chronic phase. The ongoing ASC4FIRST trial aims to compare the effectiveness of Asciminib with investigator-selected TKIs in newly diagnosed patients with chronic myeloid leukemia.
Article
Peripheral Vascular Disease
Rajiv Agarwal, Luis M. Ruilope, Gema Ruiz-Hurtado, Hermann Haller, Roland E. Schmieder, Stefan D. Anker, Gerasimos Filippatos, Bertram Pitt, Peter Rossing, Marc Lambelet, Christina Nowack, Peter Kolkhof, Amer Joseph, George L. Bakris
Summary: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, was found to reduce 24-hour, daytime, and nighttime systolic blood pressure in patients with chronic kidney disease and type 2 diabetes.
JOURNAL OF HYPERTENSION
(2023)
Editorial Material
Transplantation
Rajiv Agarwal, Denis Fouque
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Endocrinology & Metabolism
David Z. I. Cherney, Ele Ferrannini, Guillermo E. Umpierrez, Anne L. Peters, Julio Rosenstock, David R. Powell, Michael J. Davies, Phillip Banks, Rajiv Agarwal
Summary: This study assessed the efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease. The results showed that sotagliflozin 400 mg significantly reduced HbA1c at 26 weeks, while the 200 mg dose did not show significant reduction. The urine albumin-creatinine ratio decreased at 26 weeks, but the improvements were not sustained at 52 weeks. Adverse events were similar between treatment groups.
DIABETES OBESITY & METABOLISM
(2023)
Article
Cardiac & Cardiovascular Systems
Robert A. Fletcher, Clare Arnott, Patrick Rockenschaub, Aletta E. Schutte, Lewis Carpenter, Muthiah Vaduganathan, Rajiv Agarwal, George Bakris, Tara I. Chang, Hiddo J. L. Heerspink, Meg J. Jardine, Kenneth W. Mahaffey, Bruce Neal, Carol Pollock, Min Jun, Anthony Rodgers, Vlado Perkovic, Brendon L. Neuen
Summary: Using data from CANVAS and CREDENCE trials, this study found that visit-to-visit blood pressure variability is independently associated with the risks of hospitalization for heart failure and all-cause mortality in patients with type 2 diabetes and high cardiovascular risk or chronic kidney disease. However, the use of canagliflozin has little to no effect on blood pressure variability.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Oncology
Benjamin W. Corn, David B. Feldman, Ishwaria M. Subbiah, Phyllis D. Corn, Marie A. Bakitas, Robert S. Krouse, Matthew F. Hudson, Lauren A. Fowler, Valerie Fraser, Carole Siegal, Rajiv Agarwal, Jacqueline L. Ge, Jyotsana Parajuli, Jamie S. Myers, Mark A. O'Rourke
Summary: Patients prefer a communication style that combines hopefulness and realism, which can be challenging for healthcare professionals. To address this, an online workshop was developed to enhance the understanding and conveyance of hope to patients. The workshop was found to be feasible and acceptable to oncology healthcare professionals.
JNCI CANCER SPECTRUM
(2023)
Letter
Oncology
Markus Plate, Jose Jessurun, Koen van Besien
LEUKEMIA & LYMPHOMA
(2023)
Article
Transplantation
Panagiotis Georgianos, Rajiv Agarwal
Summary: Hypertension is common and poorly controlled in patients with chronic kidney disease (CKD). Accurate BP measurement is crucial. Dietary sodium restriction and the use of renin-angiotensin system blockers are recommended. Thiazide-like diuretic chlorthalidone is effective in patients with stage 4 CKD and uncontrolled hypertension.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)