Talvey (talquetamab-tgvs) / J&J - LARVOL DELTA

Practical insights into bispecific antibody therapy in multiple myeloma. (PubMed, Expert Rev Anticancer Ther) - "The rise of recent novel therapies teclistamab, elranatamab, and talquetamab for the treatment of relapsed/refractory multiple myeloma (RRMM) is a rapidly evolving area with significant clinical implications that require exploration and evaluation. Practical considerations for bispecific administration such as hospitalization requirements, monitoring of adverse events, and medication considerations are emphasized. Future directions and clinical implications regarding the pivotal role of these agents will be discussed."

Journal • Review • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

REALiTEC: A Study of Clinical Outcomes in Patients With Relapsed/Refractory Multiple Myeloma (RRMM) Treated With T-cell Redirectors Outside of Clinical Trials (clinicaltrials.gov) - P=N/A | N=600 | Recruiting | Sponsor: Janssen-Cilag Ltd. | N=280 ➔ 600

Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology

Optec: A Phase 2 Study to Evaluate Outpatient Step-up Administration of Teclistamab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results (ASH 2024) - P1, P2 | "Cytokine release syndrome (CRS) occurred in 72% of pts and 33% of pts had > 1 CRS event (grade [gr] 3, 0.6%); CRS recurrence was reduced when tocilizumab (Toci) was administered for the first CRS event compared with when it was not (20% vs 62%, respectively). Additional data and follow-up in more pts, including PK data in the first 10 pts in addition to updated infection, IVIG use, and response data will be presented at ASH. The protocol is being amended to add a cohort of Talquetamab to determine if proToci can reduce CRS and facilitate OP SUDs across bispecific antibodies."

Clinical • P2 data • Fatigue • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypotension • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Pain

Single Center Real World Experience of Talquetamab in Patients with Relapsed and Refractory Multiple Myeloma (ASH 2024) - "CRS occurred in 59.3% (n=32) of pts, (16 pts with grade 1, 15 pts with grade 2, and only 1 pt with grade 4), with 35.2% (n=19) requiring Tocilizumab. Longer follow up, larger numbers, and further biological characterization are needed to properly understand the role of Talq as bridging therapy for CART. *AFG, AG, DKH are co-first authors"

Clinical • IO biomarker • Real-world • Real-world evidence • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Oncology • Renal Disease

Generation of FcRH5xCD28 Bispecific Antibodies Synergizing with T-Cell Engagers for Enhanced Multiple Myeloma Treatment (ASH 2024) - "FcRH5xCD28 κλ bodies strongly synergized with TCEs such as Teclistamab (BCMAxCD3 bsAb) and Talquetamab (GPRC5DxCD3 bsAb) resulting in enhanced killing of MM cell lines in in vitro T-cell dependent cellular cytotoxicity assays. Importantly, significant activity is retained in the presence of soluble FcRH5 in vitro. Therefore, FcRH5xCD28 bispecific antibodies have the potential to expand the number of patients who benefit from TCE-based therapies, possibly leading to deeper and more durable responses."

Hematological Malignancies • Multiple Myeloma • Oncology

Risk Analysis of Cytokine Release Syndrome, Immune Effector Cell- Associated Neurotoxicity Syndrome, and Immune Effector Cell- Associated Hemophagocytic Lymphohistiocytosis-like Syndrome in BiTE Therapy Vs CAR-T Therapy Using Real World Data (ASH 2024) - "This study analyzed five BiTE therapies (epcoritamab, glofitamab, mosunetuzumab, teclistamab, and talquetamab) documented in the FAERS database from 2019 to February 2024. Healthcare facilities should ensure adequate resources and staff training for managing adverse events, especially when administering higher-risk therapies, leading to safer, and effective BiTE therapies. Additional analysis regarding IEC-HS will be provided at the annual meeting."

Clinical • Cytokine release syndrome • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Inflammation • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases

Frailty-Based Outcomes with Bispecific Antibodies in Older Patients with Multiple Myeloma (ASH 2024) - "The products used were teclistamab (N=43), talquetamab (N=2), and investigational agents (N=54); 67% were ≥70 and 29% were ≥75 years; 39% were female, 95% were non-Hispanic White and 4% were Black/African American. Conclusion : Frailty, defined using the simplified frailty index, was not significantly associated with inferior efficacy or increased toxicity with BsAb therapy among older patients with MM. Poor performance status predicted inferior PFS and OS, while age and comorbidity scores did not."

Clinical • Bone Marrow Transplantation • Geriatric Disorders • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Estimation of Eligibility and Response to Bispecific Antibody Therapy in US Patients with Lymphoma and Multiple Myeloma (ASH 2024) - "Excluding blinatumomab, all have gained accelerated approval through phase II trials to treat relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL); primarily diffuse large B-cell lymphoma (DLBCL and follicular lymphoma (FL), and R/R multiple myeloma (MM)...The calculated number of people eligible was multiplied by the overall response rate (ORR) reported in the trial that led to the bsAb approval for each year a therapy had an approval, using the highest calculated response, to estimate the population who would potentially benefit of these therapies.ResultsSix bsAbs were approved in the US since 2022 to treat NLH and MM : epcoritamab and glofitamab in 2023 to treat R/R DLBCL and other mature B-cell neoplasms, mosunetuzumab in 2022 and epcoritamab in 2024 to treat R/R grade 1-3A FL, and for MM, teclistamab in 2022, and elranatamab and talquetamab in 2023...Based on best available response rates from registration trials, we estimated that 9.6% and 10.5% newly diagnosed NHL..."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Efficacy of Anti-BCMA CAR-T Cell Therapies in Multiple Myeloma Patients with Prior Exposure to Bispecific Antibodies- Results from a Retrospective Multi-Center Registry Analysis (ASH 2024) - "Background Over the past years, idecabtagen-vicleucel (ide-cel) and ciltacabtagen-autoleucel (cilta-cel) have emerged as first-in-class anti-BCMA CAR-T cell therapies with unprecedented efficacy in heavily pretreated relapsed/ refractory multiple myeloma (RRMM). At the same time, our results endorse the notion that bsAb treatment should be avoided prior to T-cell apheresis. In addition, bridging should rather rely on talquetamab than teclistamab to avoid target antigen loss and ensure optimal CAR-T efficacy."

CAR T-Cell Therapy • Retrospective data • Hematological Malignancies • Multiple Myeloma • Oncology • TNFRSF17

GPRC5D Status Impacts CD38 Expression in Multiple Myeloma (ASH 2024) - "While G protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a promising antigen for TCE, newly acquired GPRC5D alterations have been reported to convey resistance to the anti-GPRC5D-CD3 TCE talquetamab...To understand the functional impact of CD38 reduction in GPRC5D models, cells were treated with the CD38 targeting immunotherapeutic agents daratumumab (Dara) and isatuximab (Isa)...Summary : This study suggests that GPRC5D alterations are associated with downregulation of CD38 at post transcriptomic level. Co-localization and clonal competition experiments are ongoing along with clinical analysis of anti-GPRC5D treated patients."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CD38 • GPRC5D • SDC1 • SLAMF7

Pharmacodynamic Signatures and Correlatives of Response in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Talquetamab or Teclistamab Plus Daratumumab and Pomalidomide (ASH 2024) - P1 | "Conclusions : Tal-DP exhibits a deep, long-term impact on efficacy through complementary mechanisms of action and may be especially beneficial in pts with prior BsAb exposure, who typically have unfavorable BL immune profiles. Ongoing analyses of tec-DP from MajesTEC-2 (NCT04722146) will be presented."

Clinical • IO biomarker • PK/PD data • Hematological Malignancies • Multiple Myeloma • Oncology • CD8 • HAVCR2 • LAG3 • PD-1

Minimal Residual Disease Measured after Treatment with Bispecifics in Relapsed Multiple Myeloma: Experience from an Academic Medical Center (ASH 2024) - "Median number of prior lines was 4 (range 1-13), 19.4% had received CAR-T previously, and 12.9% had been previously exposed to another TCE.Twenty-three pts (74.2%) were enrolled in clinical trials (7 with teclistamab, Tec, 6 with talquetamab, Tal, and 10 with investigational agents). Twelve of these pts received TCE in combination with daratumumab and/or pomalidomide...MRD- seems to translate into long PFS, regardless of HR disease. Prospective studies on fixed duration treatment with TCE based on baseline risk and treatment response are needed."

IO biomarker • Minimal residual disease • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) for Chimeric Antigen Receptor T-Cell Therapy (CAR-T) and T-Cell Engager Antibody (TCE) in Myeloma and Lymphoma (ASH 2024) - "The database was accessed on 3/1/2024 to examine the adverse effects of CAR-T using the keywords "Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome" : idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel), axicabtagene ciloleucel (axi-cel), brexucabtagene autoleucel (brexu-cel), tisagenlecleucel (tisa-cel) and lisocabtagene maraleucel (liso-cel) and TCE (teclistamab, elranatamab, talquetamab, mosunetuzumab, glofitamab, and epcoritamab) since their FDA approval in the US and non-US populations using the R software. No IEC-HS was observed with talquetamab, glofitamab, and elranatamab. However, these therapies were recently approved and not yet widely available, and longer follow-ups will be needed."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases

Combined PD-1 and Tim-3 Blockade Improves the in Vitro Anti-Myeloma Activity of T Cells of Patients on Talquetamab (ASH 2024) - P1, P2 | "We further established an in vitro assay to measure the cytotoxic capability of patient T cells obtained from different time points against the GPRC5D-expressing MM1S cell line in the presence of Tal with and without nivolumab and sabatolimab, targeting PD-1 and Tim-3, respectively. Presence of CD8+ Tem cells at baseline resulted in longer PFS, whereas more CD8+ TEMRA cells predicted shorter PFS. While our in vitro model has limitations, it shows that targeting the checkpoint markers PD-1 and Tim-3 may improve potency of BiAbs."

IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • CD8 • GPRC5D • HAVCR2 • PD-1 • SDC1

MBS314, a G Protein-Coupled Receptor Family C Group 5 Member D (GPRC5D) x B-Cell Maturation Antigen (BCMA) x CD3 Trispecific Antibody, in Relapsed and/or Refractory Multiple Myeloma (RRMM): Preliminary Results from a Phase Ⅰ, First-in-Human, Open-Label, Dose Escalation Study (ASH 2024) - P1/2 | "Background : T-cell-engaging (TCE) therapeutical antibodies, such as Teclistamab and Talquetamab have shown promising efficacy in RRMM...All four patients (100.0%) experienced grade (G) 1 cytokine release syndrome (CRS) that was cured without treatment with tocilizumab, and no G2 or higher occurred...The two pts in the 1st and 2nd dose levels achieved stable disease and partial response, respectively. Conclusion : This study demonstrated that in pts with heavily pretreated RRMM, MBS314 showed favorable safety and remarkable antitumor activity in the preliminary data, even at low doses."

Clinical • IO biomarker • P1 data • Trispecific • Cardiovascular • Hematological Malignancies • Hypertension • Multiple Myeloma • Oncology • GPRC5D

Real-World Talquetamab Utilization Patterns and Dose Schedules in the United States: An Analysis Using Claims Data (ASH 2024) - "Overall, 44.7% were naïve to prior T-cell redirection therapies, and prior exposure to commercial BCMA-targeted therapy was reported in 84 (59.6%) patients : 7.8% of patients received ciltacabtagene autoleucel, 17.7% idecabtagene vicleucel, 35.5% teclistamab (Tec), 2.1% elranatamab, and 14.2% belantamab mafodotin. Q2W was the most common dosing schedule, and some patients de-escalated to less frequent dosing. Further real-world research into Tal clinical outcomes is ongoing to provide insights into long-term use practices for this novel treatment option."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Prophylactic Dexamethasone and Remote Monitoring for Patients with Relapsed Refractory Multiple Myeloma (RRMM) Receiving Bispecific Antibodies (BsAb): Experience at a Single Institution (ASH 2024) - "Four patients developed grade 2 CRS requiring admission, of which 3 were administered a single dose of Tocilizumab...The incidence of CRS was highest following earlier SUDs; only 1 patient developed CRS after SUD #3 and SUD#4 for Teclistamab and Talquetamab, respectively...A remote monitoring program can be safely implemented in a selected population of RRMM patients with few admissions for CRS. Prophylactic dexamethasone may mitigate the risk of high-grade CRS though precautions may need to be taken in patients with certain comorbidities."

Clinical • Cardiovascular • CNS Disorders • Diabetes • Hematological Malignancies • Hypertension • Insomnia • Multiple Myeloma • Oncology • Sleep Disorder

Prognostic Factors for Survival in Multiple Myeloma Patients That Receive Bispecific Antibodies: Does Relative Dose Intensity Matters? (ASH 2024) - "Elranatamab was received by 42.5%, followed by Teclistamab (40%) and Talquetamab (17.5%). This is translated in improved PFS in this cohort. Impact of RDI on outcomes can help guide treatment length in immunotherapy."

Biomarker • Clinical • Hematological Disorders • Hematological Malignancies • Hepatology • Liver Failure • Multiple Myeloma • Neutropenia • Oncology • Renal Disease

Talquetamab in B Cell Maturation Antigen (BCMA) Exposed Relapsed-Refractory Multiple Myeloma Patients (ASH 2024) - "Our data shows that talquetamab conferred high responses in patients previously treated with BDT. However, in this cohort of pts, the immediate prior use of BDT, particularly within 6 months of talquetamab was associated with inferior outcomes."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Oncology • Thrombocytopenia • Xerostomia

Evaluating the Kinetics of Absolute Lymphocyte Counts Following Bispecific T-Cell Engager Therapy to Predict Clinical Outcomes in Relapsed/Refractory Multiple Myeloma (ASH 2024) - "Response rates were similar between anti-BCMA and non-BCMA agents, with CR/VGPR rates of 72% for elranatamab, 41% for teclistamab, and 56% for talquetamab. A delayed time to maximum deltaALC (d1-22) was a protective factor for PFS, suggesting its potential as a predictive marker for treatment outcomes. The immunobiologic mechansisms underlying this protective delayed lymphocyte expansion remain to be elucidated and further research is required to optimize the use of ALC kinetics in guiding clinical decisions in px receiving BiTEs."

Clinical • Clinical data • IO biomarker • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Prevalent Treatment Patterns of Teclistamab and Talquetamab for Multiple Myeloma (MM): Experience from 609 Patients (ASH 2024) - "However, with increasing duration of therapy, alternative dosing patterns such as Q2W, Q4W, and >Q4W schedules were observed in patients treated with teclistamab. Talquetamab was predominantly administered at a Q2W dosing schedule, albeit the shorter follow-up period."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Frailty and Outcomes after Bispecific T-Cell Engager Therapy for Patients with Relapsed/Refractory Multiple Myeloma (ASH 2024) - "Methods : Analysis included patients with RRMM who had received teclistamab, talquetamab, and/or elranatamab between December 2017 and March 2024. When compared to the non-frail group, frail patients had similar efficacy outcomes. This study highlights the tolerable safety and reasonable efficacy of BsAb for frail MM patients in a real-world practice, highlighting that frailty should not be a barrier towards the use of BsAb in this patient population."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Multiple Myeloma • Nephrology • Oncology • Renal Disease

Unmet Needs in Multiple Myeloma and Potential Solutions: A Systemic Literature Review (ASH 2024) - "Other unmet needs reported were patient and family experience/supportive care (11%), pathophysiology (4%), diagnosis/response assessment (4%), toxicity management/prevention (3%) and poor prognosis (4%).Unmet needs that were reported starting from 2010 [and their proposed solutions] include treatment of high-risk cytogenetic features (4%) [elotuzumab/isatuximab/melflufen/selinexor/anti-BCMA conjugates], treatment of plasma cell leukemia/extramedullary disease (3%) [utilizing MM drugs (daratumumab/boretezemib/melfufen/frontline ASCT etc.)], prevention/management of toxicities (mucositis, neuropathy, nephropathy and GVHD) (1%) [CR4056/amifostine/cannabidiol], treatment/prevention of thromboembolism (1%) [risk assessment model for thromboembolism/studies on anticoagulation], treatment of frail/elderly (1%) [SEA BCMA/melflufen], immune response in MM (<1%) [immunological studies], and measures to assess response to treatment (<1%) [heavy light chain ratio/DW..."

Review • Cardiovascular • Geriatric Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mucositis • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Orthopedics • Pain • Renal Disease • Respiratory Diseases

Real World Evidence of Outcomes of Patients Treated with Talquetamab in a Heavily Pretreated Population with Multiple Myeloma with High Exposure to Prior BCMA Therapies- a Report from the IMWG Consortium (ASH 2024) - "The safety profile - CRS, ICANS, skin and oral toxicities was similar to the MonumenTAL study, CMV reactivation was higher and this may be related to treatment with prior immunotherapies and should be monitored in the future. This report shows that Talq has a similar safety and efficacy profile in the real world when sequenced after prior BCMA therapies."

Clinical • HEOR • Real-world • Real-world evidence • Dental Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Pruritus • Stomatitis • Xerostomia

Late Polyclonal P-BCMA-101 CAR-T Cell Re-Expansion and Rapid Complete Response in a Patient with Relapsed Multiple Myeloma Treated with One Cycle of Talquetamab, More Than 3 Years after CAR-T Infusion (ASH 2024) - "Here, we report a case of a 57-year-old female with RRMM who initially received P-BCMA-101, a TSCM rich autologous CAR-T manufactured using the piggyBac DNA delivery system, on 8/24/20 in combination with Rituximab (375 mg/m2 on days -12, -5 and then every 8 weeks for 10 cycles) and LD (cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day on days -5, -4 and -3)...She was treated with Daratumumab, Pomalidomide and dexamethasone for ~7 months with stable disease and then Selinexor and dexamethasone for 2 months which was poorly tolerated...This is the first such report of a transposon manufactured TSCM rich CAR-T showing late and dramatic re-expansion following exposure to a TCE. This case also demonstrates that T-cell proliferations following CAR-T therapy may not always be malignant and thorough molecular analysis beyond what is the clinical standard is necessary to rule out benign processes."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • T Cell Non-Hodgkin Lymphoma • B3GAT1 • CD2 • CD4 • CD5 • CD7 • CD8 • MME • NCAM1