On December 7, 2024 bluebird bio, Inc. (Nasdaq: BLUE) reported updated data from patients with beta-thalassemia who require regular blood transfusions treated with betibeglogene autotemcel (beti-cel, approved commercially as ZYNTEGLO) in clinical studies (Press release, bluebird bio, DEC 7, 2024, View Source [SID1234648864]). The data was presented today at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"Updated follow-up data of up to 10 years showed that patients treated with beti-cel in clinical trials experienced durable transfusion independence and normal or near-normal hemoglobin, regardless of genotype and age, and a continued favorable safety profile", said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. "We are deeply grateful for the ongoing commitment of our investigators, patients, and study participants. Our collective efforts are not only advancing the field of gene therapy but also providing new hope and possibilities for individuals with severe genetic diseases."

"Data at ASH (Free ASH Whitepaper) demonstrate the durability of beti-cel through 10 years of long-term follow-up, giving additional confidence in that the transformational outcomes observed in parent studies are sustained over time," said Alexis Thompson, MD, MPH, Chief of the Division of Hematology at Children’s Hospital of Philadelphia, which is a Qualified Treatment Center for ZYNTEGLO. "These long-term data demonstrate beti-cel’s continued positive impact on iron management outcomes over time, which can help inform treatment decisions by clinicians who are now using this therapy in the real-world setting."

Betibeglogene Autotemcel (beti-cel) Gene Addition Therapy results in durable Hemoglobin A (HbA) Production with up to 10 Years of Follow-Up in Participants with Transfusion-Dependent β-Thalassemia (Poster #2194)

Long-term outcomes with beti-cel in adult and pediatric patients with TDT were presented in a poster session. The data focused on 63 adult and pediatric study participants who had received beti-cel in a Phase 1/2 or Phase 3 study. Two participants had 10 years of follow-up, and 51 (81.0%) participants had 5 or more years of follow-up. Additionally, iron status was assessed in study participants who achieved TI and discontinued chelation therapy. Results showed that majority of participants treated with beti-cel achieved TI. All participants achieved platelet and neutrophil engraftment. Specific findings showed:

Of 63 patients, 52 (90.2% in Phase 3 studies and 68.2% in Phase 1/2 studies) achieved TI. All except one patient maintained TI through last follow-up. The median weighted average hemoglobin during TI was 10.2 mg/dL for Phase 1/2 studies and 11.2 mg/dL for Phase 3 studies. Achievement and maintenance of TI and median weighted average hemoglobin were similar across ages and genotypes.
Study participants treated with beti-cel who achieved and maintained TI demonstrated effective restoration of iron homeostasis over time and reduced iron management burden. Among participants who achieved TI, improvements in serum ferritin and liver iron concentration were sustained through month 60. 28/37 (75.7%) study participants who achieved TI in Phase 3 studies are no longer undergoing iron chelation therapy.
Both adult and pediatric health-related quality of life scores (HRQoL) remained above the normative population mean up to 60 months. All 26 participants who achieved TI and completed a questionnaire reported an overall benefit with beti-cel.
The safety profile was consistent with known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. None of the study participants had a fatal event. No beti-cel–related serious adverse events were reported more than 2 years after infusion through last follow-up. No malignancies, insertional oncogenesis or vector-derived replication-competent lentivirus were reported in any study participants.
Beti-cel was approved by the FDA in August 2022 and is commercially available in the United States as ZYNTEGLO.

About ZYNTEGLO (betibeglogene autotemcel) or beti-cel

ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene therapy approved for the treatment of beta-thalassemia in adult and pediatric patients who require regular red blood cell transfusions. ZYNTEGLO works by adding functional copies of a modified form of the beta-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem and progenitor cells to enable the production of a modified functional adult hemoglobin (HbAT87Q). Once a patient has the βA-T87Q-globin gene, they have the potential to increase ZYNTEGLO-derived adult hemoglobin (HbAT87Q) and total hemoglobin to normal or near normal levels that can eliminate the need for regular red blood cell (RBC) transfusions.

Indication

ZYNTEGLO is indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions.

Important Safety Information

Delayed Platelet Engraftment

Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets on or after Day 100.

Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise.

Risk of Neutrophil Engraftment Failure

There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells.

Risk of Insertional Oncogenesis

There is a potential risk of LVV mediated insertional oncogenesis after treatment with ZYNTEGLO.

Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, and integration site analysis at Months 6, 12, and as warranted.

In the event that a malignancy occurs, contact bluebird bio at 1 833-999-6378 for reporting and to obtain instructions on collection of samples for testing.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis.

Anti-retroviral and Hydroxyurea Use

Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.

Interference with Serology Testing

Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV. Therefore, patients who have received ZYNTEGLO should not be screened for HIV infection using a PCR‑based assay.

Adverse Reactions

The most common non-laboratory adverse reactions (≥20%) were mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (>50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia.

Drug Interactions

Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates.

Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate.

Pregnancy/Lactation

Advise patients of the risks associated with conditioning agents, including on pregnancy and fertility. ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician.

ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician.

Females and Males of Reproductive Potential

A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration.

Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO.

Advise patients of the option to cryopreserve semen or ova before treatment if appropriate.

On December 7, 2024 Amgen (NASDAQ:AMGN) reported new data demonstrating that adding BLINCYTO (blinatumomab) to chemotherapy significantly improves disease-free survival (DFS) in newly diagnosed pediatric patients with National Cancer Institute (NCI) standard risk (SR) B-cell acute lymphoblastic leukemia (B-ALL) of average or higher risk of relapse (Press release, Amgen, DEC 7, 2024, View Source [SID1234648863]). The data are from a Phase 3 study (AALL1731) conducted by the Children’s Oncology Group. The results were simultaneously published in the New England Journal of Medicine and will be presented during the plenary session on Sunday, Dec. 8, at 2 p.m. PT at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego.

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"Over the last decade, BLINCYTO has reshaped the treatment landscape for B-ALL, offering a critical lifeline for thousands of adult and pediatric patients," said Jay Bradner, M.D., executive vice president of Research and Development and chief scientific officer at Amgen. "These powerful new data leave us little doubt about the profound impact of this medicine for a large number of children affected by this disease. We are grateful to the Children’s Oncology Group, along with the patients, families and clinical teams, for their dedication and partnership in advancing this critical study to improve the lives of children with cancer."

Based on the results of the first pre-specified interim analysis for efficacy, the study met its primary endpoint of DFS and study randomization was terminated early based on the recommendation from the data and safety monitoring committee due to the benefit observed in the BLINCYTO arm compared to the chemotherapy-only arm. Overall, the 3-year DFS was 96.0% for patients treated with chemotherapy plus BLINCYTO compared to 87.9% for those treated with only chemotherapy. The hazard ratio (HR) was 0.39 [95% confidence interval (CI) 0.24-0.64], indicating a 61% reduction in the risk of disease relapse, secondary malignant neoplasm or remission death with BLINCYTO. At 3 years, more patients remained alive and cancer free when treated with BLINCYTO plus chemotherapy compared to chemotherapy alone.

"The AALL1731 study results are truly practice-changing, further solidifying blinatumomab’s role as the standard of care for a large number of children with B-ALL," said Sumit Gupta, M.D., Ph.D., FRCPC, co-chair of the Children’s Oncology Group AALL1731 study and oncologist and clinician investigator, Division of Haematology/Oncology at The Hospital for Sick Children (SickKids) and associate professor of pediatrics at the University of Toronto. "These breakthrough data showing a significant improvement in disease-free survival are poised to bring substantial clinical value to children with newly diagnosed B-ALL."

The addition of BLINCYTO to chemotherapy in standard risk patients resulted in outcomes similar to those previously achieved in only the most favorable pediatric risk subsets. Among SR-Average patients, 3-year DFS was 97.5% for patients treated with BLINCYTO compared to 90.2% for those treated with only chemotherapy (HR 0.33, CI 0.15-0.69). For SR-High patients, 3-year DFS was 94.1% for those treated with BLINCYTO compared to 84.8% for those treated with only chemotherapy (HR 0.45, 95% CI 0.24-0.85).

"Relapsed ALL remains a major cause of pediatric cancer mortality, with nearly half of the relapses occurring in children with standard-risk B-ALL," said Rachel E. Rau, M.D., co-chair of the Children’s Oncology Group AALL1731 study, pediatric hematologist-oncologist at Seattle Children’s Hospital and associate professor of pediatrics at the University of Washington. "These findings underscore the progress made with blinatumomab in preventing relapse and support its role as a critical addition to current therapeutic strategies."

Safety results are consistent with the known safety profile of BLINCYTO. BLINCYTO has demonstrated a positive balance of benefits and risks, with only 0.3% of first courses associated with Grade 3+ cytokine release syndrome (CRS) and 0.7% with seizures. A higher risk of infections was observed in the BLINCYTO arm.

These results provide the first evidence supporting BLINCYTO for use in the consolidation phase in newly diagnosed pediatric Philadelphia chromosome-negative (Ph-) B-ALL patients. This groundbreaking first-in-class Bispecific T-cell Engager (BiTE) therapy is now backed by additional evidence reinforcing its role in redefining a standard of care for both adult and pediatric patients, starting from one month old, regardless of measurable residual disease (MRD) status. The findings further establish BLINCYTO as a versatile first-line consolidation therapy across all ages and treatment backbones.

The NCI’s Cancer Therapy Evaluation Program (CTEP), which sponsored the study will share data with the U.S. Food and Drug Administration as part of their ongoing communications relating to the trial.

On December 7, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported interim clinical data as of a July 5, 2024 data cutoff from the ongoing phase 1/2 trial of petosemtamab, a Biclonics targeting EGFR and LGR5, in previously treated (2L+) patients (pts) with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) (Press release, Merus, DEC 7, 2024, View Source [SID1234648857]). These data were presented by Christophe Le Tourneau MD, Ph.D., Institut Curie, Paris, France at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress on Saturday, Dec. 7 in Singapore.

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"Petosemtamab clinical data in r/m HNSCC continues to demonstrate potentially practice changing efficacy and safety, both as monotherapy in 2L+ and in combination with pembrolizumab in 1L PD-L1 expressing HNSCC," said Fabian Zohren, M.D., Ph.D., Chief Medical Officer of Merus. "Further, the monotherapy durability of petosemtamab thus far compares favorably to current standard of care, which we believe is another positive indicator for the likelihood of success of our phase 3 investigation of petosemtamab and pembrolizumab in 1L PD-L1 expressing HNSCC."

"Head and neck squamous cell carcinoma remains a deadly disease with limited treatment options," added Dr. Le Tourneau. "With its strong clinical outcomes across a large dataset of patients, regardless of HPV status and EGFR expression, petosemtamab has the potential to become a new standard of care for patients with recurrent/metastatic head and neck cancer."

Presentation title: Petosemtamab (MCLA-158) monotherapy in previously treated (2L+) recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 trial
Observations in the presentation include:

As of a July 5, 2024 data cutoff date, 82 pts were treated with petosemtamab 1500 mg Q2W
The efficacy population consists of 75 pts who had the opportunity for 4 or more months follow up and ≥1 post-baseline tumor assessment; or who discontinued early due to disease progression or death
Seven pts were not efficacy evaluable: 6 pts were previously described at AACR (Free AACR Whitepaper) 2023 and one additional patient withdrew due to infusion related reaction (IRRs) on Day 1
Confirmed overall response rate (ORR): 36% (90% CI: 27–46; 27/75) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment, including 4 complete responses (CRs), with one CR continuing on treatment for more than 3 years as of the data cutoff; and 13% (2/15) ORR in HPV associated cancer with another 5 patients achieving stable disease
At the time of data cutoff, 10 pts remain on treatment including 8 responders and 2 pts with stable disease
Median duration of response (DOR), progression free survival (PFS) and overall survival (OS) were 6.2, 4.9 and 11.4 months
For the most mature data set, the single arm cohort previously presented at AACR (Free AACR Whitepaper) 2023, as of a July 5, 2024 data cutoff, for all 54 patients, the median DOR, PFS and OS were 6.7, 5.1, and 12.0 months, respectively; among the 48 treatment evaluable subset, they were 6.7, 5.2, and 12.5 months, respectively
Petosemtamab 1500 mg Q2W continues to be well tolerated with a manageable safety profile with no new safety signals observed (82 pts)
Infusion related reactions (IRRs) were predominantly seen on day 1 of cycle 1; a clinically meaningful reduction in the incidence and severity of IRR was observed with an updated administration regimen
As of a July 5, 2024 data cutoff date, 28 pts were treated with petosemtamab 1100 mg Q2W
The efficacy population consists of 27 pts who had the opportunity for 4 or more months follow up and ≥1 post-baseline tumor assessment; or who discontinued early due to disease progression or death
One pt was not evaluable for efficacy due to withdrawing consent with <2 months treatment
ORR: 19% (90% CI: 8–35; 5/27), including 2 CRs, by RECIST v1.1. per investigator assessment
The full presentation is available on the Merus website.

Petosemtamab Clinical Development
r/m HNSCC: LiGeR-HN1 phase 3 trial in 1L and LiGeR-HN2 phase 3 trial in 2/3L enrolling; phase 2 trial of petosemtamab in combination with pembrolizumab in PD-L1+ 1L HNSCC ongoing with a clinical data update planned for 2025

mCRC: Phase 2 trial of petosemtamab in combination with standard chemotherapy in 2L metastatic colorectal cancer (mCRC) enrolling; phase 2 trial in 1L mCRC in combination with standard chemotherapy planned to initiate in 2025, and phase 2 trial in 3L+ monotherapy planned to initiate in 2025; mCRC initial clinical data planned for 2025

Company Conference Call and Webcast Information
Merus will hold a conference call and webcast for investors on December 7, 2024 at 9:00 a.m. ET. A replay will be available after the completion of the call in the Investors and Media section of our website for a limited time. 

Date & Time: Dec. 07, 2024 at 9:00 a.m. ET
Webcast link: Available on our website
Dial-in: Toll Free: 1 (800) 715-9871/ International: 1 (646) 307-1963
Conference ID: 1978503

About Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) describes a group of cancers that develop in the squamous cells that line the mucosal surfaces of the mouth, throat, and larynx. These cancers begin when healthy cells change and grow in an unchecked manner, ultimately forming tumors. HNSCC is generally associated with tobacco consumption, alcohol use and/or HPV infections, depending on where they develop geographically. HNSCC is the sixth most common cancer worldwide and it is estimated that there were more than 930,000 new cases and over 465,000 deaths from HNSCC globally in 2020.1 The incidence of HNSCC continues to rise and is anticipated to increase by 30% to more than 1 million new cases annually by 2030.2 HNSCC is a serious and life-threatening disease with poor prognosis despite currently available standard of care therapies.

1 Sung et al. CA Cancer J Clin, 71:209-49, 2021; 2 Johnson, D.E., Burtness, B., Leemans, C.R. et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6, 92 (2020)

About Petosemtamab
Petosemtamab, or MCLA-158, is a Biclonics low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.

On December 6, 2024 BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, reported the selection of 10 abstracts for poster presentations and two abstracts for online publication at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, which will be held December 7-10, 2024, in San Diego, California. BostonGene will exhibit in booth #1955 (Press release, BostonGene, DEC 6, 2024, View Source [SID1234648860]).

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"We are excited to present our research findings at ASH (Free ASH Whitepaper) that underscores the transformative potential of integrating molecular and immune profiling with advanced analytics. This approach is pivotal in advancing precision medicine and improving outcomes for individuals battling cancer," said Nathan Fowler, MD, Chief Medical Officer at BostonGene.

Details of the presentations are below:

Abstract: 1593
Title: Machine Learning-Based Approach to Improve Classification and Diagnostics of Peripheral T-Cell Lymphomas
Date & time: Saturday, December 7 | 5:30 PM -7:30 PM
Presenter: Anastasia Sobol, MS, BostonGene

BostonGene developed a machine learning-based classifier to aid in the diagnoses of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) cases. Using this transcriptomic classifier to examine over 400 cases, approximately 50% of PTCL-NOS cases were reclassified into specific subtypes based on the gene expression pattern of each sample. These findings may enhance the understanding of PTCL pathogenesis and lead to improved diagnostic methods.

Research conducted in collaboration with Weill Cornell Medicine

Abstract: 3610
Title: Novel Plasma Cell-Free RNA-Based Liquid Biopsy Approach for CLL
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Andrey Shubin, PhD, BostonGene

To address gaps in disease monitoring for chronic lymphocytic leukemia (CLL) patients, BostonGene developed a novel liquid biopsy approach based on plasma cell-free RNA (cfRNA) sequencing. From a simple blood draw, the cfDNA assay revealed malignant B-cell fractions, B-cell receptor repertoires and clinically significant mutations from cfRNA transcriptomes, as well as associations between treatment and immune- or tissue-specific processes. This liquid biopsy platform may support longitudinal monitoring CLL dynamics and minimal residual disease with further validation.

Research conducted in collaboration with Massachusetts General Hospital and Harvard Medical School

Abstract: 2981
Title: Gene Expression-Based Classifier Reclassifies Burkitt Lymphoma, HGBL NOS, DLBCL NOS, and Double/Triple Hit Lymphomas into Subtypes with More Uniform Mutational and Microenvironment Landscapes and Treatment Response
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Juan Pablo Alderuccio, MD, Sylvester Comprehensive Cancer Center at the University of Miami

A machine learning-driven, expression-based classifier was applied to high-grade B-cell lymphomas, identifying subgroups based on unique genomic and transcriptomic features. Validated using large datasets, this classifier could accurately and repeatedly divide aggressive lymphoma cases into diffuse large B-cell and Burkitt lymphoma-like groups based on gene expression. These findings illustrate the clinical applications of a gene expression-based classifier in identifying subsets of patients with aggressive lymphomas.

Research conducted in collaboration with the Sylvester Comprehensive Cancer Center at the University of Miami

Abstract: 3038
Title: Acalabrutinib with Rituximab is Highly Effective as a First Line Treatment for Older Patients with Mantle Cell Lymphoma
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Preetesh Jain, MD, MBBS, PhD, DM, The University of Texas MD Anderson Cancer Center

A phase II clinical trial for mantle cell lymphoma patients receiving acalabrutinib and rituximab demonstrated a 94% overall response rate, with 90% of patients achieving complete remission. Correlative analyses with next-generation sequencing and immunoprofiling techniques revealed key features of the immune system’s dynamics and adaptive response following treatment with the combination.

Research conducted in collaboration with the MD Anderson Cancer Center

Abstract: 2982
Title: Use of Molecular Immune Signatures for Frontline Treatment Selection in Patients with Advanced Stage Follicular Lymphoma
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Tony Zhuang, MD, MD Anderson Cancer Center

Transcriptomic analysis of pretreatment biopsies from advanced follicular lymphoma (FL) patients revealed that B-cell-associated gene signatures were linked with survival in FL patients receiving chemoimmunotherapy, while T-cell signatures correlated with improved outcomes in patients treated with lenalidomide and rituximab. These findings support the clinical application of transcriptomic profiling for FL patients.

Research conducted in collaboration with the MD Anderson Cancer Center

Abstract: 2958
Title: Circulating Tumor DNA Predicts Outcomes in Follicular Lymphoma: Analysis from a Prospective Study
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Rahul Lakhotia, MBBS, National Institutes of Health

An ongoing prospective clinical trial examined the utility of serial circulating tumor DNA (ctDNA) for monitoring disease progression in follicular lymphoma patients. Detectable in over 90% of patients, baseline ctDNA levels correlated with FLIPI prognostic scores, total metabolic tumor volume and spontaneous regression. Serial ctDNA analysis accurately reflected tumor dynamics, demonstrating its value as a minimally invasive tool for tracking disease progression.

Research conducted in collaboration with the National Cancer Institute, University of South Florida, National Institutes of Health, Medical College of Georgia, University of Virginia, Adaptive Biotechnologies

Abstract: 4341
Title: Comprehensive Analysis of Malignant B-Cell Receptors Provides Insights into B-Cell Lymphoma Pathogenesis
Date & time: Monday, December 9 | 6:00 PM – 8:00 PM
Presenter: Evgeniia Alekseeva, PhD, BostonGene

Aimed at characterizing B-cell receptor (BCR) repertoires, BostonGene leveraged a blood-based approach to discover biomarkers capable of distinguishing B-cell lymphoma subtypes. Several features, including BCR isotype, IGVH somatic hypermutation rate and chain structure, were associated with specific subtypes, highlighting the potential for diagnostic biomarkers within BCR repertoires.

Abstract: 4377
Title: Radiation Therapy and Monocyte Activation in Large B-cell Lymphoma Patients Treated with CAR T-Cell Therapy
Date & time: Monday, December 9 | 6:00 PM – 8:00 PM
Presenter: Penny Fang, MD Anderson Cancer Center

A study evaluating CART-treated large B-cell lymphoma (LBCL) patients revealed radiation therapy reshapes the immune landscape, particularly by increasing monocyte levels, proliferation and cytotoxicity. This shift suggested radiation therapy is a viable bridging therapy for CART LBCL patients, promoting a suppressive immunotype linked with decreased toxicity and increased treatment response.

Research conducted in collaboration with the MD Anderson Cancer Center

Abstract: 4348
Title: Genomic and Spatial Proteomic Characterization of the Microenvironment of Diffuse Large B-Cell Lymphoma in African American Patients
Date & time: Monday, December 9 | 6:00 PM – 8:00 PM
Presenter: Michelle Lee, MD, PhD, Winship Cancer Institute of Emory University

A flagship multiomics study characterizing diffuse large B-cell lymphoma (DLBCL) in African American patients revealed the prevalence of immune-inflamed microenvironments, molecular alterations and distinct spatial cellular communities. These findings suggest tumor-specific factors may drive the disparity in survival outcomes and underscore the need for larger, more diverse clinical cohorts.

Research conducted in collaboration with the Winship Cancer Institute of Emory University, MD Anderson Cancer Center and Georgia Institute of Technology

Abstract: 4364
Title: Evaluating the clinical utility of comprehensive whole exome sequencing (WES) and RNA-seq for patients with lymphoma
Date & time: Monday, December 9 | 6:00 PM – 8:00 PM
Presenter: Dai Chihara, MD, PhD, MD Anderson Cancer Center

The BostonGene Tumor PortraitTM test, featuring integrated genomic and transcriptomic profiling, was used to generate clinically relevant findings, treatment recommendations and matched clinical trials for lymphoma patients. With a median turnaround time of just 8 days, the Tumor PortraitTM test’s robust findings and rapid turnaround time demonstrated the utility of integrated whole exome and transcriptome sequencing for lymphoma patients.

Research conducted in collaboration with the MD Anderson Cancer Center

Online only
Title: Tumor Genomics and Microenvironment Characterization of Diffuse Large B-Cell Lymphoma in Asian and Pacific Islander Patients

Integrated whole exome and transcriptome sequencing was performed on diffuse large B-cell lymphoma (DLBCL) tumors from the Hawaii Surveillance, Epidemiology, and End Results residual tissue repository, constituting an initial characterization of the DLBCL microenvironment in Asian and Pacific Islander patients, an under-represented population in prior studies. The findings suggest existing classification systems may not represent DLBCL heterogeneity in non-European populations, illustrating the need for studies with more diverse patient populations to reveal how ancestry, socioeconomic elements and environmental factors contribute to DLBCL pathobiology and outcomes.

Research conducted in collaboration with the Winship Cancer Institute of Emory University and MD Anderson Cancer Center

Title: Comprehensive Molecular Characterization of Monomorphic Post-Transplant Lymphoproliferative Disorder (PTLD)

Comparative analysis of Epstein-Barr virus (EBV)-positive and -negative post-transplant lymphoproliferative disorder (PTLD) patients with diffuse large B-cell lymphoma (DLBCL) uncovered distinct immune signatures and a higher prevalence of protumor elements among EBV-positive PTLD patients. When compared with immunocompetent-DLBCL, PTLD samples contained a higher fraction of plasma B-cells. While EBV-negative PTLDs largely resembled de novo DLBCLs, EBV-positive PTLDs were enriched with unique molecular features. These findings emphasize the role of EBV status in PTLD biology and associated clinical outcomes.

Research conducted in collaboration with the MD Anderson Cancer Center

In addition to the poster presentations, the abstracts have been published online in the November supplemental issue of "Blood."

On December 6, 2024 Indapta Therapeutics, Inc., a privately held clinical stage biotechnology company developing next-generation differentiated cell therapies for the treatment of cancer and autoimmune diseases, reported a collaboration with Sanofi to explore the combination of its allogeneic g-NK cell therapy, IDP-023, with Sanofi’s CD38-targeting monoclonal antibody, Sarclisa (isatuximab) (Press release, Indapta Therapeutics, DEC 6, 2024, View Source [SID1234648859]).

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Indapta has amended its ongoing phase 1 study of IDP-023, to add a cohort of IDP-023 in combination with Sarclisa for patients with relapsed/refractory multiple myeloma. Up to three dose levels of IDP-023 will be explored in the combination.

Under the agreement, Indapta will sponsor the clinical trial, Sanofi will supply Sarclisa, and the Parties will co-fund the trial. As presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Meeting, IDP-023 administered with or without interleukin-2 achieved a mean maximum reduction in serum M-protein or light chain of 73% in eight relapsed/refractory myeloma patients. This appears to be superior to prior trials of natural killer cells in myeloma.

"With its deep experience in multiple myeloma and pipeline of products in hematologic malignancies and immunologic disorders, Sanofi is an excellent partner to help Indapta develop our differentiated natural killer cell product," said Robert Sikorski, Indapta’s Chief Medical Officer. "We look forward to a close collaborative relationship and leveraging Sanofi’s expertise in the design of potential subsequent studies."

Indapta’s Proprietary g-NK Cell Therapy

Indapta’s universal, allogeneic NK cell therapy platform consists of a potent subset of naturally occurring NK cells, known as "g minus" NK cells, or "g-NK" cells. g-NK cells arise from epigenetic changes resulting from exposure to cytomegalovirus (CMV). To generate IDP-023, Indapta preferentially expands g-NK cells from healthy donors, with low donor to donor variability. IDP-023 has several differentiated mechanisms of killing target cells without the need for genetic engineering, including highly robust antibody-dependent cell mediated cytotoxicity (ADCC), the targeting of HLA-E expressing cells via the NKG2C receptor, and the inherent anti-viral activity of g-NK cells.

Indapta’s g-NK can release dramatically more immune activating cytokines and cell-killing compounds than conventional NK cells. In preclinical studies, IDP-023 has demonstrated more potent and durable antitumor activity when combined with cancer targeting monoclonal antibodies as compared to conventional NK cells. (Bigley et al., Blood Advances 2021, View Source). g-NK cells in combination with a B cell targeting antibody can also deplete normal B cells from healthy donors or patients with autoimmune disease.