Hematology Commons^™

Persistence Of Pet Scan Positivity After Chemoimmunotherapy For Dlbcl, James O. Armitage, Matthew A. Lunning, Julie M. Vose, Dan L. Longo

Journal Articles: Oncology and Hematology

Approximately 80% of patients with diffuse large B-cell lymphoma achieve a complete response after chemoimmunotherapy as defined by positron emission tomography (PET) scan. However, not all patients who fail to achieve a metabolic complete response are destined to relapse. In a number of these patients, the PET scan is falsely positive (ie, 20%-40% in several large series), particularly when the PET scan has a Deauville score of 4. Reflexively intervening with salvage systemic therapy or radiotherapy in these patients is potentially harmful. It seems that very sensitive measurements of circulating tumor DNA might be able to differentiate between patients who …

Isatuximab Plus Bortezomib, Lenalidomide, And Dexamethasone For Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: A Frailty Subgroup Analysis Of The Imroz Trial, Salomon Manier, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Philippe Moreau, Michele Cavo, Hartmut Goldschmidt, Robert Z Orlowski, Muriel Tron, Christina Tekle, Marie-France Brégeault, Andrea T Shafer, Meral Beksac, Thierry Facon

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg …

Phase 2 Trial Of Ibrutinib And Nivolumab In Patients With Relapsed Cns Lymphomas, Dai Chihara, Raphael E Steiner, Ranjit Nair, Lei Feng, Sairah Ahmed, Paolo Strati, Luis Malpica, Donna P Griffith, Shivon A Mathew, Wirt Montinez, Gita Masand, Felipe Samaniego, Maria A Rodriguez, Fredrick B Hagemeister, Luis E Fayad, Swaminathan P Iyer, Loretta J Nastoupil, Sattva S Neelapu, Christopher R Flowers, Jason R Westin

Faculty, Staff and Student Publications

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Previous studies have shown the activity of Bruton tyrosine kinase inhibitors and programmed death-1-targeted therapies in CNS lymphoma, and studies suggested potential synergy. Therefore, we conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received 560 mg oral ibrutinib daily with 240 mg IV nivolumab every 14 days (28 days per cycle). Patients who had partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years …

Long Term Results Of Venetoclax Combined With Flag-Ida Induction And Consolidation For Newly Diagnosed And Relapsed Or Refractory Acute Myeloid Leukemia, Courtney D Dinardo, Wei-Ying Jen, Koichi Takahashi, Tapan M Kadia, Sanam Loghavi, Naval G Daver, Lianchun Xiao, Patrick K Reville, Ghayas C Issa, Nicholas J Short, Koji Sasaki, Sa A Wang, Jillian K Mullin, Sherry Pierce, Corey Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Alessandra Ferrajoli, Mahesh Swaminathan, Maro Ohanian, Hussein A Abbas, Danielle Hammond, Jan Burger, Fadi Haddad, Guillermo Montalban-Bravo, Kelly Chien, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Intensive chemotherapy remains the standard for newly diagnosed (ND) acute myeloid leukemia (AML); however, relapse risk remains high. Additionally, most patients with relapsed/refractory (RR) AML have poor outcomes. We report the long-term experience of 138 patients, 77 ND and 61 RR, treated with FLAG-IDA in combination with venetoclax. In the ND cohort, the overall response rate (ORR) was 97%, with a composite complete remission (CRc) rate of 95% and undetectable measurable residual disease (MRD) status by flow cytometry in 90%. The 3-year OS and EFS rates were 66 and 64%, respectively. Outcomes were similar across European LeukemiaNet (ELN) 2022 risk …

Oral Decitabine Cedazuridine With And Without Venetoclax In Higher-Risk Myelodysplastic Syndromes Or Chronic Myelomonocytic Leukemia: A Propensity Score-Matched Study, Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James Mccloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched …

Oral Decitabine Cedazuridine With And Without Venetoclax In Higher-Risk Myelodysplastic Syndromes Or Chronic Myelomonocytic Leukemia: A Propensity Score-Matched Study, Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James Mccloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched …

Superior Preclinical Efficacy Of Co-Treatment With Brg1/Brm And Flt3 Inhibitor Against Aml Cells With Flt3 Mutations, Warren Fiskus, Christopher P Mill, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Patrick K Reville, Lauren B Flores, Sanam Loghavi, Xiaoping Su, Courtney D Dinardo, Kapil N Bhalla

Faculty, Staff and Student Publications

Although treatment with standard frontline therapies, including a FLT3 inhibitor (FLT3i) reduces AML burden and achieves clinical remissions, most patients with AML with FLT3 mutation relapse due to therapy-resistant stem/progenitor cells. The core ATPases, BRG1 (SMARCA4) and BRM (SMARCA2) of the canonical (c) BAF (BRG1/BRM-associated factor) complex is a dependency in AML cells, including those harboring FLT3 mutations. We have previously reported that treatment with FHD-286, a BRG1/BRM ATPases inhibitor, induces differentiation and loss of viability of AML stem/progenitor cells. Findings of present studies demonstrate that treatment with FHD-286 induces lethality in AML cells, regardless of sensitivity or resistance to …

Efficacy And Safety Of Venetoclax Plus Azacitidine For Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes, Jacqueline S Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). …

A Phase 1 Study Of Durvalumab As Monotherapy Or Combined With Tremelimumab With Or Without Azacitidine In Patients With Myelodysplastic Syndrome, Guillermo Garcia-Manero, Manila Gaddh, Uwe Platzbecker, R Coleman Lindsley, Sarah M Larson, Timothy Chevassut, Pierre Fenaux, Rami Komrokji, Roger Lyons, Aref Al-Kali, Yu Jiang, John Bothos, Danielle M Townsley, Amer M Zeidan

Faculty, Staff and Student Publications

Upregulation of programmed death ligand-1 (PD-L1) has been observed in patients with MDS, and its expression on myeloblasts is associated with progression to AML. This open-label, phase 1 study evaluated the safety and tolerability of the PD-L1 antibody durvalumab as monotherapy (part 1) and in combination with tremelimumab, with or without azacitidine (part 2), in patients with MDS who progressed following hypomethylating agent treatment. Sixty-seven adults with MDS were enrolled (part 1, 40 with low/intermediate-1 or intermediate-2/high IPSS risk status; part 2, 27 with intermediate-2/high IPSS risk status). Primary safety endpoints included dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). …

Impact Of Measurable Residual Disease Clearance Kinetics In Patients With Aml Undergoing Intensive Chemotherapy, Wei-Ying Jen, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Sa A Wang, Wei Wang, Sanam Loghavi, Naval G Daver, Courtney D Dinardo, Ghayas C Issa, Hussein A Abbas, Cedric Nasnas, Alex Bataller, Samuel Urrutia, Omer S Karrar, Sherry Pierce, Hagop M Kantarjian, Nicholas J Short

Faculty, Staff and Student Publications

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) …

Mayo Genetic Risk Models For Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent, Naseema Gangat, Azeem Elbeih, Nour Ghosoun, Kristen Mccullough, Fnu Aperna, Isla M Johnson, Maymona Abdelmagid, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Michelle Elliott, Abhishek Mangaonkar, Aasiya Matin, Antoine N Saliba, Mehrdad Hefazi Torghabeh, Mark R Litzow, William Hogan, Mithun Shah, Mrinal M Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Samuel Yates, Abigail Sneider, Emily Dworkin, Anand A Patel, Alexandre Bazinet, Jayastu Senapati, Alex Bataller, Courtney Dinardo, Tapan Kadia, Ayalew Tefferi

Faculty, Staff and Student Publications

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis-derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar, 1.7 for TP53

Mutation- And Mrd-Informed Treatments For Transplant-Ineligible Patients, Curtis A Lachowiez, Courtney D Dinardo

Faculty, Staff and Student Publications

The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups. Furthermore, the simultaneous discovery of resistance mechanisms to targeted therapies and AZA-VEN has enabled the identification of patient subgroups with inferior outcomes, …

Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine, Hartmut Döhner, Keith W Pratz, Courtney D Dinardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most …

Alliance A061202: Ixazomib, Pomalidomide, And Dexamethasone For Patients With Lenalidomide-Refractory Mm In First Relapse., Peter Voorhees, Vera Suman, Yvonne Efebera, Noopur Raje, Sascha Tuchman, Cesar Rodriguez, Jacob Laubach, Misty Bova-Solem, Destin Carlisle, Saad Usmani, Philip Mccarthy, Paul G Richardson

Oncology Articles

Optimal therapy for the growing number of patients with lenalidomide (LEN)-refractory multiple myeloma in their first relapse remains poorly defined. We therefore undertook a randomized phase 2 study to evaluate the efficacy and safety of combining the oral proteasome inhibitor ixazomib (IXA) with pomalidomide (POM) and dexamethasone (DEX) in this patient population. The overall response rate (ORR) for POM-DEX was 43.6%, and for IXA-POM-DEX, it was 63.2%. The depth of response, measured by the attainment of at least a very good partial response, favored triplet therapy over doublet therapy (28.9% vs 5.1%; P = .0063). A preplanned interim analysis after …

Daratumumab In Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma: Final Analysis Of Clinically Relevant Subgroups In Griffin, Ajai Chari, Jonathan L Kaufman, Jacob Laubach, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Rebecca Silbermann, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a …

Polatuzumab Vedotin, Venetoclax, And An Anti-Cd20 Monoclonal Antibody In Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, Sam Yuen, Tycel J Phillips, Rajat Bannerji, Paula Marlton, Giuseppe Gritti, John F Seymour, Anna Johnston, Christopher Arthur, Anna Dodero, Sunil Sharma, Jamie Hirata, Lisa Musick, Christopher R Flowers

Faculty, Staff and Student Publications

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed-dose obinutuzumab 1000 mg or rituximab 375 mg/m2 in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), respectively. Patients with complete response (CR) or partial response (PR)/stable disease (FL) or CR/PR (DLBCL) at end of induction (EOI; six 21-day cycles) received post-induction therapy with venetoclax and obinutuzumab or rituximab, respectively. Primary endpoint was CR rate at EOI. Safety-evaluable populations included 74 patients (FL cohort; median age 64 years; progression of disease within 24 months …

A Multicenter Study Of Venetoclax-Based Treatment For Patients With Richter Transformation Of Chronic Lymphocytic Leukemia, Paul J Hampel, Mahesh Swaminathan, Kerry A Rogers, Erin M Parry, Jan A Burger, Matthew S Davids, Wei Ding, Alessandra Ferrajoli, Jonathan M Hyak, Nitin Jain, Saad S Kenderian, Yucai Wang, William G Wierda, Jennifer A Woyach, Sameer A Parikh, Philip A Thompson

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and …

Proteomics For Optimizing Therapy In Acute Myeloid Leukemia: Venetoclax Plus Hypomethylating Agents Versus Conventional Chemotherapy, Eduardo Sabino De Camargo Magalhães, Stefan Edward Hubner, Brandon Douglas Brown, Yihua Qiu, Steven Mitchell Kornblau

Faculty, Staff and Student Publications

The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, …

Reduced Dose Azacitidine Plus Venetoclax As Maintenance Therapy In Acute Myeloid Leukaemia Following Intensive Or Low-Intensity Induction: A Single-Centre, Single-Arm, Phase 2 Trial, Alexandre Bazinet, Hagop Kantarjian, Alex Bataller, Naveen Pemmaraju, Gautam Borthakur, Kelly Chien, Yesid Alvarado, Prithviraj Bose, Elias Jabbour, Musa Yilmaz, Courtney Dinardo, Ghayas Issa, Guillermo Montalban-Bravo, Nicholas Short, Koji Sasaki, Debra Bull-Linderman, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Background: Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia.

Methods: We performed a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center in the USA. Eligible …

Safety And Efficacy Of A New High-Dose Regimen Of Panobinostat, Gemcitabine, Busulfan, And Melphalan For 1st Or 2nd Salvage Asct For Refractory/Relapsed Or High-Risk Myeloma: Matched-Pair Comparisons With Concurrent Control Cohorts, Yago Nieto, Zixi Yang, Benigno C Valdez, Suprateek Kundu, Qaiser Bashir, Jeremy Ramdial, Samer Srour, Muzaffar Qazilbash

Faculty, Staff and Student Publications

Improvement of autologous stem-cell transplantation (ASCT) for myeloma is needed. Building on our prior work, we prospectively evaluated panobinostat and gemcitabine/busulfan/melphalan (GemBuMel) with ASCT in this population. Patients aged 18-65 years with relapsed/refractory or high-risk myeloma and adequate end-organ function were eligible. Treatment included panobinostat (20 mg/day, days -9 to -2) and GemBuMel (days -8 to -2). Patients were enrolled in 1st (ASCT-1) or 2nd ASCT (ASCT-2) cohorts. We compared their outcomes with all our other concurrent ASCT patients who met eligibility criteria but received melphalan or BuMel off study, matched for age, prior therapy lines, high-risk cytogenetics, and response …

Impact Of Cumulative Dose Of Brentuximab Vedotin On Outcomes Of Frontline Therapy For Advanced-Stage Hodgkin Lymphoma, Raphael E Steiner, Steven R Hwang, Arushi Khurana, Thomas M Habermann, Narendranath Epperla, Kaitlin Annunzio, Pamela Blair Allen, Katelin Baird, Darina Paulino, Juan Pablo Alderuccio, Izidore S Lossos, Kevin David, Andrew M Evens, Karan Pandya, Steven M Bair, Manali Kamdar, Sheeba Ba Aqeel, Pallawi Torka, Ryan Lynch, Stephen Smith, Lei Feng, Mansoor Noorani, Sairah Ahmed, Ranjit Nair, Francisco Vega, Susan Wu, Penny Fang, Chelsea C Pinnix, Jillian R Gunther, Bouthaina S Dabaja, Hun J Lee

Faculty, Staff and Student Publications

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and …

Integrative Analysis Of Clinicopathological Features Defines Novel Prognostic Models For Mantle Cell Lymphoma In The Immunochemotherapy Era: A Report From The North American Mantle Cell Lymphoma Consortium, Julie M Vose, Kai Fu, Lu Wang, Adnan Mansoor, Douglas Stewart, Hongxia Cheng, Lynette Smith, Ji Yuan, Hina Naushad Qureishi, Brian K Link, Melissa H Cessna, Paul M Barr, Brad S Kahl, Matthew S Mckinney, Nadia Khan, Ranjana H Advani, Peter Martin, Andre H Goy, Tycel J Phillips, Amitkumar Mehta, Manali Kamdar, Michael Crump, Barbara Pro, Christopher R Flowers, Caron A Jacobson, Sonali M Smith, Deborah M Stephens, Veronika Bachanova, Zhaohui Jin, Shishou Wu, Francisco Hernandez-Ilizaliturri, Pallawi Torka, Andrea Anampa-Guzmán, Farshid Kashef, Xing Li, Sunandini Sharma, Timothy C Greiner, James O Armitage, Matthew Lunning, Dennis D Weisenburger, Robert G Bociek, Javeed Iqbal, Guohua Yu, Chengfeng Bi, North American Mantle Cell Lymphoma Consortium

Faculty, Staff and Student Publications

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.

METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed …

Influence Of Treatment Intensity And Medical Comorbidities In Older Adults With Peripheral T Cell Lymphoma, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Samuel Ng, Alexey V Danilov, Swaminathan Iyer, Sharon H Giordano

Faculty, Staff and Student Publications

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71-83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N …

Sustained Remissions In Cll After Frontline Fcr Treatment With Very-Long-Term Follow-Up, Philip A Thompson, Alexandre Bazinet, William G Wierda, Constantine S Tam, Susan M O'Brien, Satabdi Saha, Christine B Peterson, William Plunkett, Michael J Keating

Faculty, Staff and Student Publications

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) achieves durable remissions, with flattening of the progression-free survival (PFS) curve in patients with mutated immunoglobulin heavy chain variable gene (IGHV-M). We updated long-term follow-up results from the original 300-patient FCR study initiated at MD Anderson in 1999. The current median follow-up is 19.0 years. With this extended follow-up, the median PFS for patients with IGHV-M was 14.6 years vs 4.2 years for patients with unmutated IGHV (IGHV-UM). Disease progression beyond 10 years was uncommon. In total, 16 of 94 (17%) patients in remission at 10 years subsequently progressed with the additional follow-up …

A Randomized Phase Iii Study Of Standard Versus High-Dose Cytarabine With Or Without Vorinostat For Aml, Guillermo Garcia-Manero, Nikolai A Podoltsev, Megan Othus, John M Pagel, Jerald P Radich, Min Fang, David A Rizzieri, Guido Marcucci, Stephen A Strickland, Mark R Litzow, M Lynn Savoie, Bruno C Medeiros, Mikkael A Sekeres, Tara L Lin, Geoffrey L Uy, Bayard L Powell, Jonathan E Kolitz, Richard A Larson, Richard M Stone, David Claxton, James Essell, Selina M Luger, Sanjay R Mohan, Anna Moseley, Frederick R Appelbaum, Harry P Erba

Faculty, Staff and Student Publications

Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 …

Evolving Trends And Outcomes In Older Patients With Acute Myeloid Leukemia Including Allogeneic Stem Cell Transplantation, Alexandre Bazinet, Hagop Kantarjian, Naszrin Arani, Uday Popat, Alex Bataller, Koji Sasaki, Courtney D Dinardo, Naval Daver, Musa Yilmaz, Hussein A Abbas, Nicholas J Short, Ghayas Issa, Elias Jabbour, Sherry A Pierce, Julianne Chen, Ricky Garcia, Marina Konopleva, Guillermo Garcia-Manero, Amin Alousi, Elizabeth J Shpall, Richard E Champlin, Gautam Borthakur, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Outcomes in older patients with acute myeloid leukemia (AML) have historically been poor. Given advances in low-intensity therapy (LIT) and stem cell transplantation (SCT), we performed a retrospective single-center study to evaluate the contemporary outcomes of this population. We reviewed all patients ≥60 years with newly diagnosed AML between 2012 and 2021 and analyzed treatment and SCT-related trends and outcomes. We identified 1073 patients with a median age of 71 years. Adverse clinical and cytomolecular findings were frequent within this cohort. In total, 16% of patients were treated with intensive chemotherapy, 51% with LIT alone, and 32% with LIT plus …

Impact Of Detectable Monoclonal Protein At Diagnosis On Outcomes In Marginal Zone Lymphoma: A Multicenter Cohort Study, Narendranath Epperla, Qiuhong Zhao, Reem Karmali, Pallawi Torka, Lauren Shea, Timothy S. Oh, Andrea Anampa-Guzmán, Heather Reves, Montreh Tavakkoli, Irl Brian Greenwell, Emily Hansinger, Elvira Umyarova, Kaitlin Annunzio, Yazeed Sawalha, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Natalie S. Grover, Adam J Olszewski

Department of Medicine Faculty Papers

Given the paucity of data surrounding the prognostic relevance of monoclonal paraprotein (M-protein) in marginal zone lymphoma (MZL), we sought to evaluate the impact of detecting M-protein at diagnosis on outcomes in patients with MZL in a large retrospective cohort. The study included 547 patients receiving first-line therapy for MZL. M-protein was detectable at diagnosis in 173 (32%) patients. There was no significant difference in the time from diagnosis to initiation of any therapy (systemic and local) between the M-protein and no M-protein groups. Patients with M-protein at diagnosis had significantly inferior progression-free survival (PFS) compared with those without M-protein …

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 …

A Phase 1/2 Study Of Azacitidine, Venetoclax And Pevonedistat In Newly Diagnosed Secondary Aml And In Mds Or Cmml After 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 …

Mini-Hyper-Cvd Plus Inotuzumab Ozogamicin, With Or Without Blinatumomab, In The Subgroup Of Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphocytic Leukaemia: Long-Term Results Of An Open-Label Phase 2 Trial, Elias Jabbour, Nicholas J Short, Jayastu Senapati, Nitin Jain, Xuelin Huang, Naval Daver, Courtney D Dinardo, Naveen Pemmaraju, William Wierda, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Koji Sasaki, Tapan M Kadia, Joseph Khoury, Sa A Wang, Fadi G Haddad, Jovitta Jacob, Rebecca Garris, Farhad Ravandi, Hagop M Kantarjian

Faculty, Staff and Student Publications

Background: The outcome of older patients with B-cell acute lymphocytic leukaemia is inferior to that in younger patients due to the adverse disease biology and their inability to tolerate intensive therapy. We aimed to study the long-term outcomes of inotuzumab ozogamicin with or without blinatumomab in combination with low-intensity chemotherapy in these patients.

Methods: For this open-label phase 2 trial, patients aged 60 years or older with newly diagnosed, Philadelphia-chromosome negative, B-cell acute lymphocytic leukaemia, and an ECOG performance status of 3 or lower were eligible. This study was conducted at the University of Texas MD Anderson Cancer Center. The …