Hemic and Lymphatic Diseases Commons^™

Real-World Experience Of Patients With Multiple Myeloma Receiving Ide-Cel After A Prior Bcma-Targeted Therapy, Christopher J Ferreri, Michelle A T Hildebrandt, Hamza Hashmi, Leyla O Shune, Joseph P Mcguirk, Douglas W Sborov, Charlotte B Wagner, M Hakan Kocoglu, Aaron Rapoport, Shebli Atrash, Peter M Voorhees, Jack Khouri, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, Larry D Anderson, Gary Simmons, James A Davis, Nilesh Kalariya, Lauren C Peres, Yi Lin, Murali Janakiram, Omar Nadeem, Melissa Alsina, Frederick L Locke, Surbhi Sidana, Doris K Hansen, Krina K Patel, Omar Alexis Castaneda Puglianini

Faculty, Staff and Student Publications

Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior …

Venous Thromboembolism Risk In Cancer Patients Receiving First-Line Immune Checkpoint Inhibitor Versus Chemotherapy, Ang Li, Sarah B May, Jennifer La, Kylee L Martens, Christopher I Amos, Christopher R Flowers, Nhan V Do, Mary T Brophy, Vipul Chitalia, Katya Ravid, John Michael Gaziano, Nathanael R Fillmore

Faculty, Staff and Students Publications

It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)-weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first-line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer …

Impact Of Type Of Induction Therapy On Outcomes In Older Adults With Aml After Allogeneic Stem Cell Transplantation, Nicholas J Short, Faustine Ong, Farhad Ravandi, Graciela Nogueras-Gonzalez, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Marina Konopleva, Gautam Borthakur, Betul Oran, Gheath Al-Atrash, Rohtesh Mehta, Elias J Jabbour, Musa Yilmaz, Ghayas C Issa, Abhishek Maiti, Richard E Champlin, Hagop Kantarjian, Elizabeth J Shpall, Uday Popat

Faculty, Staff and Student Publications

Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC; n = 44), lower-intensity therapy (LIT) without venetoclax (n = 29), or LIT with venetoclax (n = 54) and who underwent allogeneic HSCT in the first remission. The 2-year relapse-free survival …

A Phase 1/2 Study Of Azacitidine, Venetoclax And Pevonedistat In Newly Diagnosed Secondary Aml And In Mds Or Cmmlafter Failure Of Hypomethylating Agents, Nicholas J Short, Muharrem Muftuoglu, Faustine Ong, Lewis Nasr, Walid Macaron, Guillermo Montalban-Bravo, Yesid Alvarado, Mahesh Basyal, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Maro Ohanian, Elias Jabbour, Ghayas C Issa, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Keyur P Patel, Prithviraj Bose, Farhad Ravandi, Ricardo Delumpa, Regina Abramova, Guillermo Garcia-Manero, Michael Andreeff, Jorge Cortes, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax.

METHODS: This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m

FINDINGS: Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61-86 years), and …

Mitophagy Promotes Resistance To Bh3 Mimetics In Acute Myeloid Leukemia, Christina Glytsou, Xufeng Chen, Emmanouil Zacharioudakis, Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou, Michael Cammer, Kun Wang, Tomasz Zal, Malgorzata Anna Zal, Bing Z Carter, Jo Ishizawa, Raoul Tibes, Aristotelis Tsirigos, Michael Andreeff, Evripidis Gavathiotis, Iannis Aifantis

Faculty, Staff and Student Publications

BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 …

A Phase I Study Of Milademetan (Ds3032b) In Combination With Low Dose Cytarabine With Or Without Venetoclax In Acute Myeloid Leukemia: Clinical Safety, Efficacy, And Correlative Analysis, Jayastu Senapati, Muharrem Muftuoglu, Jo Ishizawa, Hussein A Abbas, Sanam Loghavi, Gautam Borthakur, Musa Yilmaz, Ghayas C Issa, Samuel I Dara, Mahesh Basyal, Li Li, Kiran Naqvi, Rasoul Pourebrahim, Elias J Jabbour, Steven M Kornblau, Nicholas J Short, Naveen Pemmaraju, Guillermo Garcia-Manero, Farhad Ravandi, Joseph Khoury, Naval Daver, Hagop M Kantarjian, Michael Andreeff, Courtney D Dinardo

Faculty, Staff and Student Publications

In TP53 wild-type acute myeloid leukemia (AML), inhibition of MDM2 can enhance p53 protein expression and potentiate leukemic cell apoptosis. MDM2 inhibitor (MDM2i) monotherapy in AML has shown modest responses in clinical trials but combining options of MDM2i with other potent AML-directed agents like cytarabine and venetoclax could improve its efficacy. We conducted a phase I clinical trial (NCT03634228) to study the safety and efficacy of milademetan (an MDM2i) with low-dose cytarabine (LDAC)±venetoclax in adult patients with relapsed refractory (R/R) or newly diagnosed (ND; unfit) TP53 wild-type AML and performed comprehensive CyTOF analyses to interrogate multiple signaling pathways, the p53-MDM2 …

Targeted Therapy With The Mutant Idh2 Inhibitor Enasidenib For High-Risk Idh2-Mutant Myelodysplastic Syndrome, Courtney D Dinardo, Sangeetha Venugopal, Curtis Lachowiez, Koichi Takahashi, Sanam Loghavi, Guillermo Montalban-Bravo, Xuemei Wang, Hetty Carraway, Mikkael Sekeres, Ameenah Sukkur, Danielle Hammond, Kelly Chien, Abhishek Maiti, Lucia Masarova, Koji Sasaki, Yesid Alvarado, Tapan Kadia, Nicholas J Short, Naval Daver, Gautam Borthakur, Farhad Ravandi, Hagop M Kantarjian, Bhumika Patel, Amy Dezern, Gail Roboz, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

The isocitrate dehydrogenase enzyme 2 (IDH2) gene is mutated in ∼5% of patients with myelodysplastic syndrome (MDS). Enasidenib is an oral, selective, mutant IDH2 inhibitor approved for IDH2-mutated (mIDH2) relapsed/refractory acute myeloid leukemia. We designed a 2-arm multicenter study to evaluate safety and efficacy of (A) the combination of enasidenib with azacitidine for newly diagnosed mIDH2 MDS, and (B) enasidenib monotherapy for mIDH2 MDS after prior hypomethylating agent (HMA) therapy. Fifty patients with mIDH2 MDS enrolled: 27 in arm A and 23 in arm B. Median age of patients was 73 years. The most common adverse events were neutropenia (40%), …

A Phase 2 Study Of Nivolumab Combined With Ibrutinib In Patients With Diffuse Large B-Cell Richter Transformation Of Cll, Nitin Jain, Jayastu Senapati, Beenu Thakral, Alessandra Ferrajoli, Philip Thompson, Jan Burger, Sreyashi Basu, Tapan Kadia, Naval Daver, Gautam Borthakur, Marina Konopleva, Naveen Pemmaraju, Erin Parry, Catherine J Wu, Joseph Khoury, Carlos Bueso-Ramos, Naveen Garg, Xuemei Wang, Wanda Lopez, Ana Ayala, Susan O'Brien, Hagop Kantarjian, Michael Keating, James Allison, Padmanee Sharma, William Wierda

Faculty, Staff and Student Publications

Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of …

Endovascular Vs Medical Management For Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis Of Clear And Rescue-Japan, James E Siegler, Muhammad M Qureshi, Raul G Nogueira, Kanta Tanaka, Simon Nagel, Patrik Michel, Nicholas Vigilante, Marc Ribo, Hiroshi Yamagami, Shinichi Yoshimura, Mohamad Abdalkader, Diogo C Haussen, Mahmoud H Mohammaden, Stefania Nannoni, Markus A Möhlenbruch, Hilde Henon, Sunil A Sheth, Santiago Ortega-Gutierrez, Marta Olive-Gadea, Francois Caparros, Fatih Seker, Syed Zaidi, Alicia C Castonguay, Kazutaka Uchida, Nobuyuki Sakai, Ajit S Puri, Mudassir Farooqui, Kazunori Toyoda, Sergio Salazar-Marioni, Masataka Takeuchi, Behzad Farzin, Hesham E Masoud, Anna Luisa Kuhn, Ameena Rana, Masafumi Morimoto, Masunari Shibata, Tadashi Nonaka, Piers Klein, Anvitha Sathya, Nicole L Kiley, Charlotte Cordonnier, Davide Strambo, Jelle Demeestere, Peter A Ringleb, Daniel Roy, Osama O Zaidat, Tudor G Jovin, Johannes Kaesmacher, Urs Fischer, Jean Raymond, Thanh N Nguyen

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO.

METHODS: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from …

Association Of Endovascular Thrombectomy Vs Medical Management With Functional And Safety Outcomes In Patients Treated Beyond 24 Hours Of Last Known Well, Amrou Sarraj, Timothy J Kleinig, Ameer E Hassan, Pere Cardona Portela, Santiago Ortega-Gutierrez, Michael G Abraham, Nathan W Manning, James E Siegler, Nitin Goyal, Laith Maali, Spiros Blackburn, Teddy Y Wu, Jordi Blasco, Arturu Renú, Navdeep S Sangha, Juan F Arenillas, Margy E Mccullough-Hicks, Adam Wallace, Daniel Gibson, Deep K Pujara, Faris Shaker, Mercedes De Lera Alfonso, Marta Olivé-Gadea, Mudassir Farooqui, Juan S Vivanco Suarez, Zachary Iezzi, Jane Khalife, Colleen G Lechtenberg, Syed K Qadri, Rami B Moussa, Mohammad A Abdulrazzak, Tareq S Almaghrabi, Osman Mir, James Beharry, Balaji Krishnaiah, Megan Miller, Najwa Khalil, Gagan J Sharma, Aristeidis H Katsanos, Ali Fadhil, Kelsey R Duncan, Yin Hu, Sheryl B Martin-Schild, Georgios K Tsivgoulis, Dennis Cordato, Anthony Furlan, Leonid Churilov, Peter J Mitchell, Adam S Arthur, Mark W Parsons, James C Grotta, Clark W Sitton, Marc Ribo, Gregory W Albers, Bruce C V Campbell

Faculty, Staff and Student Publications

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.

OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or …

Association Of Endovascular Thrombectomy Vs Medical Management With Functional And Safety Outcomes In Patients Treated Beyond 24 Hours Of Last Known Well, Amrou Sarraj, Timothy J Kleinig, Ameer E Hassan, Pere Cardona Portela, Santiago Ortega-Gutierrez, Michael G Abraham, Nathan W Manning, James E Siegler, Nitin Goyal, Laith Maali, Spiros Blackburn, Teddy Y Wu, Jordi Blasco, Arturu Renú, Navdeep S Sangha, Juan F Arenillas, Margy E Mccullough-Hicks, Adam Wallace, Daniel Gibson, Deep K Pujara, Faris Shaker, Mercedes De Lera Alfonso, Marta Olivé-Gadea, Mudassir Farooqui, Juan S Vivanco Suarez, Zachary Iezzi, Jane Khalife, Colleen G Lechtenberg, Syed K Qadri, Rami B Moussa, Mohammad A Abdulrazzak, Tareq S Almaghrabi, Osman Mir, James Beharry, Balaji Krishnaiah, Megan Miller, Najwa Khalil, Gagan J Sharma, Aristeidis H Katsanos, Ali Fadhil, Kelsey R Duncan, Yin Hu, Sheryl B Martin-Schild, Georgios K Tsivgoulis, Dennis Cordato, Anthony Furlan, Leonid Churilov, Peter J Mitchell, Adam S Arthur, Mark W Parsons, James C Grotta, Clark W Sitton, Marc Ribo, Gregory W Albers, Bruce C V Campbell

Faculty, Staff and Student Publications

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.

OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or …

Smart Start: Rituximab, Lenalidomide, And Ibrutinib In Patients With Newly Diagnosed Large B-Cell Lymphoma, Jason Westin, R Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Hun Ju Lee, Luis Fayad, Loretta Nastoupil, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy Mcdonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W Scott, Christopher R Flowers, Sattva Neelapu, Michael R Green

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset.

METHODS: We enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m

RESULTS: The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. …

Improved Outcomes With “7+3” Induction Chemotherapy For Acute Myeloid Leukemia Over The Past Four Decades: Analysis Of Swog Trial Data, Megan Othus, Guillermo Garcia-Manero, John E Godwin, James K Weick, Frederick R Appelbaum, Harry P Erba, Elihu H Estey

Faculty, Staff and Student Publications

We have previously shown that complete response (CR) rates and overall survival of patients with acute myeloid leukemia have improved since the 1980s. However, we have not previously evaluated how the length of first CR (CR1) has changed over this time period. To address this, we analyzed 1,247 patients aged 65 or younger randomized to "7+3" arms from five SWOG studies: S8600 (n=530), S9031 (n=98), S9333 (n=57), S0106 (n=301), and S1203 (n=261). We evaluated length of CR1 and survival after relapse from CR1 over the four decades that these studies represent. Both length of CR1 and survival after relapse from …

Phase Ii Study Of Venetoclax Added To Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine In Older Patients With Newly Diagnosed Acute Myeloid Leukemia, Tapan M Kadia, Patrick K Reville, Xuemei Wang, Caitlin R Rausch, Gautam Borthakur, Naveen Pemmaraju, Naval G Daver, Courtney D Dinardo, Koji Sasaki, Ghayas C Issa, Maro Ohanian, Guillermo Montalban-Bravo, Nicholas J Short, Nitin Jain, Alessandra Ferrajoli, Kapil N Bhalla, Elias Jabbour, Koichi Takahashi, Rashmi Malla, Kelly Quagliato, Rashmi Kanagal-Shamanna, Uday R Popat, Michael Andreeff, Guillermo Garcia-Manero, Marina Y Konopleva, Farhad Ravandi, Hagop M Kantarjian

Faculty, Staff and Student Publications

PURPOSE: The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.

METHODS: This is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with …

Targeting The Eif2ak1 Signaling Pathway Rescues Red Blood Cell Production In Sf3b1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts, Vera Adema, Feiyang Ma, Rashmi Kanagal-Shamanna, Natthakan Thongon, Guillermo Montalban-Bravo, Hui Yang, Scott A Peslak, Feng Wang, Pamela Acha, Francesc Sole, Pamela Lockyer, Margherita Cassari, Jaroslaw P Maciejewski, Valeria Visconte, Irene Gañán-Gómez, Yuanbin Song, Carlos Bueso-Ramos, Matteo Pellegrini, Tuyet M Tan, Rafael Bejar, Jennifer S Carew, Stephanie Halene, Valeria Santini, Gheath Al-Atrash, Karen Clise-Dwyer, Guillermo Garcia-Manero, Gerd A Blobel, Simona Colla

Faculty, Staff and Student Publications

SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks of a specific MDS subtype, MDS with ringed sideroblasts (MDS-RS), which is characterized by the accumulation of erythroid precursors in the bone marrow and primarily affects the elderly population. Here, using single-cell technologies and functional validation studies of primary SF3B1-mutant MDS-RS samples, we show that SF3B1 mutations lead to the activation of the EIF2AK1 pathway in response to heme deficiency and that targeting this pathway rescues aberrant erythroid differentiation and enables the red blood cell maturation of MDS-RS erythroblasts. These data support the development of …

Clonal Hematopoiesis Is Associated With Higher Risk Of Stroke, Romit Bhattacharya, Seyedeh M Zekavat, Jeffrey Haessler, Myriam Fornage, Laura Raffield, Md Mesbah Uddin, Alexander G Bick, Abhishek Niroula, Bing Yu, Christopher Gibson, Gabriel Griffin, Alanna C Morrison, Bruce M Psaty, William T Longstreth, Joshua C Bis, Stephen S Rich, Jerome I Rotter, Russell P Tracy, Adolfo Correa, Sudha Seshadri, Andrew Johnson, Jason M Collins, Kathleen M Hayden, Tracy E Madsen, Christie M Ballantyne, Siddhartha Jaiswal, Benjamin L Ebert, Charles Kooperberg, Joann E Manson, Eric A Whitsel, Nhlbi Trans-Omics For Precision Medicine Program, Pradeep Natarajan, Alexander P Reiner

Faculty, Staff and Student Publications

Background and purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke.

Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association …

Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Gavin Cull, Jan A Burger, Stephen Opat, David Gottlieb, Emma Verner, Judith Trotman, Paula Marlton, Javier Munoz, Patrick Johnston, David Simpson, Jennifer C Stern, Radha Prathikanti, Kenneth Wu, William Novotny, Jane Huang, Constantine S Tam

Faculty, Staff and Student Publications

The phase I/II AU-003 study in patients with treatment-naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow-up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response …

Randomized Phase Iii Bmt Ctn Trial Of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions In Myeloablative Hematopoietic Cell Transplantation For Hematologic Malignancies, Leo Luznik, Marcelo C Pasquini, Brent Logan, Robert J Soiffer, Juan Wu, Steven M Devine, Nancy Geller, Sergio Giralt, Helen E Heslop, Mary M Horowitz, Richard J Jones, Mark R Litzow, Adam Mendizabal, Lori Muffly, Eneida R Nemecek, Lynn O'Donnell, Richard J O'Reilly, Raquel Palencia, Johannes Schetelig, Leyla Shune, Scott R Solomon, Sumithira Vasu, Vincent T Ho, Miguel-Angel Perales

Faculty, Staff and Students Publications

PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).

METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or …

Prediction Of Early (4-Week) Mortality In Acute Myeloid Leukemia With Intensive Chemotherapy, Koji Sasaki, Tapan Kadia, Kebede Begna, Courtney D Dinardo, Gautam Borthakur, Nicholas J Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Lucia Masarova, Sherry Pierce, Marina Konopleva, Farhad Ravandi, Ayalew Tefferi, Hagop Kantarjian

Faculty, Staff and Student Publications

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was …