EMBARGOED
Newswise — Many physician-scientists and other researchers from Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine will be making oral or poster presentations or participating in panel discussions at the American Society of Hematology’s 2023 annual meeting in San Diego, Dec. 9-12.
Below is an EMBARGOED summary highlighting several presentations involving Sylvester physicians and other staff members.
Please note that all information is strictly embargoed until the date and time of each presentation.
Lymphomas
EMBARGOED UNTIL Monday, December 11, 2023: 5:45 PM, Grand Hall C
Presenting Author: Juan Pablo Alderuccio, MD, Sylvester Comprehensive Cancer Center
Intro: No standard-of-care exists for treatment of relapsed/refractory follicular lymphoma (FL) with worse prognosis in those demonstrating progression of disease within 24 months from frontline immunochemotherapy. Loncastuximab tesirine (loncastuximab) is an antibody-drug conjugate comprising a monoclonal antibody. The authors report results of a single-institution, investigator-initiated study evaluating this combination for the first time to treat FL. Conclusion: A limited duration program combining loncastuximab with rituximab in patients with FL is well tolerated and highly effective for high-risk patients or those with high disease burden.
EMBARGOED UNTIL Sunday, December 10, 2023: 5:00 PM
Presenting Author: Trent Wang, DO, MPH, Sylvester Comprehensive Cancer Center
Intro: There are limited reported outcomes of patients with large B-cell lymphoma (LBCL) who are infused with CD19 CAR-T cells while being in radiographic or metabolic complete remission (CR). The authors hypothesize that these patients in complete remission before CAR-T infusion may have favorable progression-free survival with lower toxicity.
Conclusion: CAR-T cell in LBCL patients who are CR after receiving two or more lines of prior therapy is a reasonable consolidation option, with a subset of patients remaining progression-free at two years. Their 9% rate of non-relapse mortality highlights the importance of continued follow-up.
EMBARGOED UNTIL Monday, December 11, 2023: 5:45 PM
Presenting Author: Jay Y. Spiegel, MD, FRCPC, Sylvester Comprehensive Cancer Center
Intro: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 CAR T-cell therapy that induces durable responses in patients with relapsed or refractory large B-cell lymphoma. The authors previously reported outcomes for axi-cell patients treated with standard-of-care therapy, including 42% who were ineligible for the ZUMA-1 trial. Now, they update outcomes for this cohort at 58 months.
Conclusion: This multicenter, retrospective study showed similar five-year results to the ZUMA-1 trial, despite including patients ineligible for that trial due to comorbidities. It supports the curative potential of axi-cel therapy but highlights the risk for non-relapse mortality in this group.
EMBARGOED UNTIL Saturday, December 9, 2023: 5 PM
Presenting Author: Jorge A. Florindez, MD, University of North Carolina School of Medicine
Sylvester Authors: Izidore S. Lossos, MD, and Juan Pablo Alderuccio, MD
Intro: Some patients with follicular or marginal zone lymphoma experience high-grade transformation (HGT) into diffuse large B-cell lymphoma. This study used population-based data to assess incidence and risk factors for HGT, post-HGT overall survival and lymphoma-specific survival across subtypes with treatment or surveillance as initial strategies.
Conclusion: Frontline treatment was associated with lower risk for HGT in follicular lymphoma, with advanced stage and female gender identified as risk factors. For other lymphomas, initial treatment neither diminished HGT risk nor improved survival afterward.
Myelodysplastic Syndromes/Neoplasms
EMBARGOED UNTIL Monday, December 11, 2023: 4:45 PM
Presenting Author: Luca Lanino, MD, Humanitas Clinical and Research Center, Milano, Italy
Sylvester Authors: Mikkael A. Sekeres, MD, Justin Taylor, MD and Stephen D. Nimer, MD
Intro: Significant discrepancies still exist between WHO and ICC classifications of myelodysplastic syndromes/neoplasms, despite their recent inclusion of gene mutations and chromosomal abnormalities to enhance diagnosis and clinical decision-making. These differences potentially cause inconsistent practices within the clinical setting. This study for the International Consortium for MDS adopted a data-driven model to develop a harmonization road map for these classifications.
Conclusion: The study demonstrated the value of this approach based on advanced statistical methods to generate harmonized MDS classifications.
EMBARGOED UNTIL Monday, December 11, 2023: 11:45 AM
Presenting Author: Justin Watts, MD, Sylvester Comprehensive Cancer Center
Intro: Bromodomain and extra-terminal (BET) proteins regulate expression of critical oncoproteins associated with myelofibrosis (MF) and other blood-cancer malignancies, including B-lymphoma-2. This ongoing Phase 1, dose-escalation study is evaluating the safety and tolerability of a BET inhibitor as monotherapy and in combination with ruxolitinib.
Conclusion: Monotherapy and combination therapy with ruxolitinib were generally well-tolerated, except for the largest monotherapy amount that caused two dose-limiting toxicities. Dose-finding for both therapies is ongoing to determine the recommended expansion dose.
EMBARGOED UNTIL Saturday, December 9, 2023: 5:30-7:30 PM, Halls G-H (San Diego Convention Center)
Senior Author: Justin M. Watts, MD, Sylvester Comprehensive Cancer Center (Presenting author is Jorge Cortes, MD, Georgia Cancer Center, Augusta)
Intro: Olutasidenib, a small molecule drug that targets a mutation involved in certain cancers and is approved for relapsed and refractory acute myeloid leukemia (AML), was studied in 22 patients with a specific type of myelodysplastic syndromes/neoplasms (MDS).
Conclusion: In this subgroup of patients in a Phase 1/2 study, the drug – used both alone and in combination with another drug – induced durable remissions in patients with intermediate-, high-, or very high-risk MDS, and the treatment had a tolerable and manageable safety profile.
EMBARGOED UNTIL Saturday, December 9, 2023: 5:30-7:30 PM, Halls G-H (San Diego Convention Center)
Senior Author: Mikkael A. Sekeres, MD, Sylvester Comprehensive Cancer Center (Presenter: Amy E. DeZern, MD, Johns Hopkins University)
Intro: Myelodysplastic syndromes (MDS) – disorders of blood cells in the bone marrow – may result from mutations in stem cells responsible for blood cell creation. Screening and monitoring of some diseases can be accomplished by assessing mutations in peripheral blood, from a basic blood draw, but because the ability to detect and monitor mutations involved with MDS and related conditions is less certain, guidelines often require invasive bone marrow evaluations instead.
Conclusion: This study, which included 36 patients, compared results from peripheral blood and bone marrow studies and found that peripheral blood can be used to reliably identify somatic (non-hereditary) mutations in patients with suspected or established MDS and related conditions.
EMBARGOED UNTIL Monday, December 11, 2023: 6-8 PM, Halls G-H (San Diego Convention Center)
Sylvester Co-Authors: Mikkael A. Sekeres, MD, and Namrata Sonia Chandhok, MD, Sylvester Comprehensive Cancer Center (Presenting Author: Jan Philipp Bewersdorf, MD, Memorial Sloan Kettering Cancer Center)
Intro: This multicenter analysis aimed to provide a better understanding of treatment options for patients with cancers of blood cells in the bone marrow – higher-risk myelodysplastic syndromes/neoplasms (HR-MDS). Two drugs, azacitidine and decitabine, both hypomethylating agents, or HMA, provide the foundation of mainstay, frontline treatments for HR-MDS, but they have not been compared directly in randomized trials.
Conclusion: This study, involving 1,223 patients, with 919 patients included in the survival analysis, found no significant difference in overall survival or overall responses between the two groups of patients treated with the drugs.
44 Altered RNA Export in SF3B1 Mutants Increases Sensitivity to Nuclear Export Inhibition
EMBARGOED UNTIL Saturday, December 9, 2023: 9:45 AM
First Presenter: Sana Chaudhry, Sylvester Comprehensive Cancer Center
Senior Author: Justin Taylor, MD, Sylvester Comprehensive Cancer Center
Intro: About half of MDS patients carry genetic alterations, known as somatic mutations, in spliceosome genes, with SF3B1 being the most commonly mutated one. However, no successful therapy exists to target this pathway. The authors hypothesized that XPO1 inhibition may preferentially affect these mutant cells via splicing, and that high-risk MDS patients with this mutation would have a better response to rational drug combinations with next-generation XPO1 inhibitors.
Conclusion: The study provides insight on the mechanisms behind the increased effectiveness of XPO1 inhibition in SF3B1-mutant MDS and leukemia patients. These findings also may contribute to development of potentially beneficial drug combinations.
Leukemias
EMBARGOED UNTIL Sunday, December 10, 2023: 4:30-5:45 PM, Room 6CF (San Diego Convention Center
Presenting Author: Justin M. Watts, MD, Sylvester Comprehensive Cancer Center
Description: This Education Session will review the transformation in AML therapy from traditional 7+3 for fit patients and hypomethylating agents for unfit patients to new standards of care and ongoing questions in the field. We will discuss the data regarding the development of hypomethylating agents plus venetoclax as the new standard of care for older patients and those not eligible for induction chemotherapy. There is growing interest in the use of HMA/Ven combinations for younger and fit patients and in specific subsets of AML; limited data in these patient populations and ongoing clinical trials will be reviewed. Resistance to HMA/Ven therapy remains a significant concern, and recent data regarding mechanisms of resistance and potential strategies to overcome ven resistance will be addressed. Given the FDA approval of several targeted agents in AML since 2017, there is a need to understand and optimize the use of these medications in combinations with traditional AML therapy. Questions regarding combinations, sequencing and management of toxicities will be discussed. Optimization of 7+3 chemotherapy in specific subsets of AML will be reviewed, including 7+3 based combinations with FLT3 inhibitors or gemtuzumab, as well as the use of CPX-351 in older patients with secondary AML and recent data in other AML patient populations.
EMBARGOED UNTIL Sunday, December 10, 2023: 6-8 PM, Halls G-H (San Diego Convention Center)
Senior Author: Justin M. Watts, MD, Sylvester Comprehensive Cancer Center (Presenter: Jorge Cortes, MD, Georgia Cancer Center, Augusta)
Intro: Olutasidenib, a small molecule drug approved for treatment of relapsed and refractory acute myeloid leukemia, targets a specific mutation that exists in these cancers. It is being studied in subsets of patients whose disease returned after treatment with stem cell transplant or the drugs ivosidenib (IVO) or venetoclax (VEN). The research team is conducting post-study analyses to better understand the response to olutasidenib in these poor-prognosis subgroups.
Conclusion: Olutasidenib alone or in combination with a drug called azacitidine may induce complete remissions in patients with this type of AMD or myelodysplastic syndromes/neoplasms (MDS) that was relapsing or refractory to VEN, IVO or even hematopoietic stem cell transplant. This supports further study in larger groups of difficult-to-treat patients.
EMBARGOED UNTIL Monday, December 11, 2023: 4 PM
Presenting Author: Esther Natalie Oliva, MD, U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
Senior Author: Mikkael A. Sekeres, MD, Sylvester Comprehensive Cancer Center
Intro: QuANTUM-First, a global, Phase 3 clinical trial evaluated the safety and effectiveness of the novel oral inhibitor quizartinib in combination with standard first-line and consolidation chemotherapy, and as a maintenance monotherapy for adults with acute myeloid leukemia (AML). While quizartinib showed clinically meaningful improvements in overall survival, an exploratory endpoint assessed its impact on patient-reported outcomes. The authors report the first longitudinal results of these outcomes.
Conclusion: Quizartinib showed improvement in overall survival without any detrimental impact on quality of life and symptoms when added to standard chemotherapy, followed by maintenance monotherapy in newly diagnosed AML patients.
Lung Cancer
2649 Predictors and Timing of Venous Thromboembolism in Lung Cancer
EMBARGOED UNTIL Sunday, December 10, 2023: 6-8 PM, Halls G-H (San Diego Convention Center)
Presenter: Thomas Plate IV, MD, Sylvester Comprehensive Cancer Center (all authors affiliated with Sylvester and/or University of Miami)
Intro: Venous thromboembolism (VTE), the blockage of a blood vessel by a clot, is a common complication in lung cancer, and physicians often prescribe blood thinners for prevention, but there’s uncertainty about true incidence, risk factors and effects of treatments with various subtypes of lung cancer. Sylvester researchers analyzed data from their tumor registry to identify patients diagnosed with lung cancer between 2018 and 2022 and assess venous thromboembolism events and related factors.
Conclusion: The retrospective study found an increased risk of VTE among patients treated for lung cancer and determined that the development of thrombosis was associated with a significantly decreased overall survival. Every subgroup of patients was at high risk of developing VTE. Statistical analyses showed that VTE and other factors including age, gender, cancer stage, and blood counts were significant predictors of death.
Myeloid Malignancies
EMBARGOED UNTIL Saturday, December 9, 2023: 5:30-7:30 PM, Halls G-H (San Diego Convention Center)
Senior Author: Justin Taylor, MD, Sylvester Comprehensive Cancer Center (Additional Sylvester co-authors: Namrata Sonia Chandhok, MD, [co-first author] and Justin M. Watts, MD) (Presenting author: Jan Philipp Bewersdorf, MD, Memorial Sloan Kettering Cancer Center)
Intro: Researchers at Sylvester and Memorial Sloan Kettering have studied the effects of an experimental drug, E7820, in patients with relapsing or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) that result from mutations in certain genes. Preclinical data from their work shows a synergy between E7820 and a drug called venetoclax.
Conclusion: Based on preclinical data, the researchers plan to amend their current Phase 2 study to include a separate arm of E7820 in combination with venetoclax – a combination that has never been studied in human AML and MDS patients.
Multiple Myeloma
210 Efficacy and Safety of Daratumumab (DARA) Monotherapy in Patients with Intermediate-Risk or High-Risk Smoldering Multiple Myeloma (SMM): Final Analysis of the Phase 2 Centaurus Study EMBARGOED UNTIL Saturday, December 9, 2023: 3:15 PM, Harbor Ballroom (Manchester Grand Hyatt San Diego) Presenting Author: Ola Landgren, MD, Sylvester Comprehensive Cancer Center Intro: Smoldering multiple myeloma (SMM) is a precursor disorder to multiple myeloma (MM). Current guidelines recommend only active monitoring for SMM, with treatment beginning only when it progresses to MM, but therapeutic intervention at the earlier stage may help delay progression to MM. Investigators in this multicenter collaboration hypothesized that daratumumab (DARA), a monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, could delay progression of SMM to MM. Preliminary results of the Phase 2 CENTAURUS study were previously reported. Here, the researchers present the final analysis. Conclusion: Findings from the final analysis continue to demonstrate the clinical activity of DARA monotherapy in patients with intermediate- or high-risk SMM after a median follow-up of approximately seven years. No new safety concerns were observed.
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