Elrexfio (elranatamab-bcmm) / Pfizer - LARVOL DELTA

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

Elranatamab in Patients with Daratumumab Relapsed and/or Refractory Light Chain Amyloidosis (ASH 2024) - "B-cell maturation antigen (BCMA)-targeting bispecific T-cell engagers (BiTEs), Teclistimab and Elranatamab have shown rapid and durable responses in RRMM with a lower incidence and severity of cytokine release syndrome (CRS) compared to chimeric antigen receptor T-cell therapies...CRS occurred within 24 hours of the first priming dose, lasted two days, and resolved with IV fluids, tocilizumab, and dexamethasone without recurrence...Elranatamab was well-tolerated with no added toxicity and acceptable safety profile. These data support Elranatamab's use in relapsed/refractory AL amyloidosis and prospective studies using BCMA-targeting BiTEs in this high-risk, high-need population."

Clinical • Amyloidosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Reducing Time Toxicity for Anti-B-Cell Maturation Antigen (BCMA) Bispecific Treatment: Evidence from Pivotal Single-Arm Trial Data on Teclistamab, Elranatamab, and Linvoseltamab for Triple-Class Exposed (TCE) Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2024) - "Conclusions : Extended dosing intervals with BCMA bsAbs can substantially reduce time toxicity for patients with RRMM. Linvoseltamab had the lowest number of TRC days among BCMA bsAbs."

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

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

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

Reducing Infection Risks of Anti-BCMA Bispecific Antibodies in Multiple Myeloma: In-Hospital Vs. Hospital-at-Home Treatment (ASH 2024) - "Materials and Methods : This study included all triple-class and penta-refractory MM patients treated with teclistamab or elranatamab at ten Greater Paris University Hospitals (AP-HP) from July 2022 to January 2024...Amoxicillin prophylaxis was more common in the HaH cohort than in the inpatient cohort (58% vs. 28%; p<0.05). TMP-SMX and antiviral prophylaxis rates were similar between cohorts (p=not significant [NS])...The HaH cohort had higher complete response rates (56% vs. 31.2%) and very good partial response rates (28% vs. 11.4%) compared to inpatients, with similar partial response rates (16% vs. 16.5%). Conclusion : This study demonstrates that BsAb treatment in HaH is a safe and effective alternative for MM patients, associated with a lower risk of grade ≥ 3 infections."

Clinical • IO biomarker • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Neutropenia • Oncology • Renal Disease

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

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

Infection Risk and Efficacy of Anti-BCMA Bispecific Antibodies in Multiple Myeloma: A Real-World Propensity Score-Matched Study (ASH 2024) - "Adverse Events : Cytokine release syndrome occurred in 50.2% of BsAb patients (2% grade ≥ 3); 38.6% required tocilizumab. However, appropriate prevention, including immunoglobulin therapy, can reduce this risk and improve patients' survival. Teclistamab and elranatamab showed similar toxicity profiles."

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

Real-World Utilization of Bispecific Antibodies for Treatment of Relapsed/Refractory Multiple Myeloma in the US Community Oncology Setting (ASH 2024) - "The most commonly observed BsAb was teclistamab (received by 183 patients, 91% of the BsAb population), followed by talquetamab (n=28, 14%) and elranatamab (n=6, 3%). Characteristics of patients receiving BsAbs were generally in line with broader rrMM population statistics. As the first analysis of the real-world uptake of BsABs in a national network of community practices, findings from this study set the stage for a more in-depth analysis of characteristics of patients receiving these treatments compared to those who do not, as well as longer-term outcome analysis when sufficient follow-up is available."

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

Clearance of Circulating Multiple Myeloma Cells to Assess Early Response to Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma (ASH 2024) - "Currently, two BCMA-targeting BsAbs (teclistamab and elranatamab) and one GPRC5D-targeting BsAb (talquetamab) have regulatory approval for the treatment of patients (pts) with RRMM. Conclusions : CMMC counts through serial peripheral blood sampling can be used to assess disease burden and early kinetics of response to BsAb therapy. Further follow-up and additional cohorts are planned to confirm performance of this assay as a biomarker in predicting response and long-term outcomes in patients receiving BsAb and other therapies, as well as interrogating mechanisms of resistance through targeted sequencing and analysis of tumor-associated antigens of enumerated cells."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • PTPRC • SDC1

Tumor Intrinsic and Antigen-Independent Resistance Mechanisms to Bispecific T Cell Engagers in Multiple Myeloma (ASH 2024) - "Cytotoxicity evaluation of anti-BCMA (teclistamab, elranatamab) or anti-GPRC5D (talquetamab) TCEs at E : T ratio of 1 : 1 against TRAF3ko MM cells (chronically exposed to PBMC only) versus the TRAF3ko-R cells demonstrated a ≥10 fold increase in the IC50 in TRAF3ko-R cells. Importantly we identified novel tumor intrinsic and antigen independent mediators of resistance to TCEs. These studies revealed a surprising multimodal dynamic tumoral adaptation primarily driven by an attenuation of UPR signaling and ensuing downregulation of multiple intrinsic and extrinsic apoptotic pathways as well as mediators of non-apoptotic immunogenic cell death."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • ATF3 • ATF4 • BBC3 • CEBPB • CHAC1 • ERN1 • MAP3K14 • PMAIP1 • TNFRSF10B • TNFRSF17 • TRIB3

Updated Results of a Matching-Adjusted Indirect Comparison of Elranatamab Versus Teclistamab in Patients with Triple-Class Exposed/Refractory Multiple Myeloma (ASH 2024) - P2 | "Among patients who achieved ≥CR, ELRA showed significantly longer OS, PFS, and DoR. These results suggest that ELRA continues to be an effective option for treating patients with TCE MM."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Prophylaxis and Vaccinations for Infections with BCMA and GPRC5D T-Cell Engagers in Multiple Myeloma: Usmirc Practice Patterns (ASH 2024) - "All centers offered both teclistamab and talquetamab, and 7 also used elranatamab...Other vaccines were used less frequently : Prevnar 20 (33%), Pentavalent (DPT, Hep B, H.influenzae) (27%), Hep B virus (27%), RZV (27%), MCV4 (20%), Pneumovax 23 (20%), HPV (20%), MMR live (20%) and VZV live (6%)...While there are limitations in the generalizability of these practices, these findings demonstrate several areas with varying clinical practices across USMIRC centers. Further studies are needed to correlate these practices with infection rates and to allow development of consensus guidelines for both academic and community centers."

Cytomegalovirus Infection • Hematological Disorders • Hematological Malignancies • Hepatitis B • Infectious Disease • Influenza • Multiple Myeloma • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections • CD4

Steric Hindrance By APRIL in Binding of BCMA-Directed Bispecific Antibodies: A Novel Refractory Mechanism of BCMA-Directed Immunotherapies in Multiple Myeloma (ASH 2024) - "mBCMA is shed off as soluble BCMA (sBCMA) by γ-secretase; treatment with the γ-secretase inhibitor RO4929097 substantially increased mBCMA levels on MM cells while reducing sBCMA...We further investigated the effects of APRIL on binding of the anti-BCMA/anti-CD3 bispecific Abs, teclistamab and elranatamab to BCMA in MM cells...Therefore, APRIL derived from OCs might cause steric hindrance of BCMA from anti-BCMA Ab binding and alleviate the efficacy of immunotherapies targeting BCMA. Further study is warranted to overcome the resistant mechanisms for BCMA-directed immunotherapies."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CXCL12 • CXCR4 • SDC1 • TNFRSF17

Predictive Markers for Outcomes after Disease Progression Post BCMA-Directed CAR T-Cell Therapy in Patients with Relapsed or Refractory Multiple Myeloma (ASH 2024) - "BACKGROUND Idecabtagene vicleucel (I) and Ciltacabtagene autoleucel (C) are two commercially available BCMA-directed CAR-T cell products initially FDA approved after > 4 lines of therapy in patients with triple class exposed relapsed or refractory multiple myeloma patients (RRMM)...Treatment at progression was categorized as follows : combination therapy (CT including alkylating agents, proteasome inhibitors, immunomodulatory agents, BCL2 inhibitors, XPO1 inhibitors, monoclonal antibodies), BCMA bispecific antibody (teclistamab, elranatamab), GPRC5D bispecific antibody (talquetamab), BCMA antibody-drug conjugate (ADC) (belantamab) and clinical trial...High-risk cytogenetics and high tumor burden at the time of progression are associated with worse outcomes in these patients. The post progression use of either BCMA or GPRC5D bispecific antibody is associated with improved outcomes as compared to combination chemotherapy"

Biomarker • CAR T-Cell Therapy • Clinical • IO biomarker • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology

BCMA Extracellular Domain Functional Hotspots and Resistance to Variable Anti-BCMA T Cell Engagers in Multiple Myeloma (ASH 2024) - "K562 cells stably transduced to express wild type (wt) or mutant BCMA (50 clones) were screened for surface BCMA expression by flow cytometry, as well as teclistamab, elranatamab, and alnuctamab binding and cytotoxicity in cocultures with peripheral blood mononuclear cells. In summary, we herein established a dictionary of BCMA functional hotspots and characterized their differential impact on anti-BCMA TCE binding and cytotoxicity. These results will not only support the rational design of future anti-BCMA agents but also guide the clinical sequencing of anti-BCMA therapies."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • TNFRSF17

Tocilizumab Prophylaxis for Patients with Relapsed or Refractory Multiple Myeloma Treated with Teclistamab, Elranatamab or Talquetamab (ASH 2024) - "J Clin Oncol 2023) and the investigational bispecific antibody cevostamab (Trudel et al...A single repeat dose of tocilizumab was given for ICANS and additional dexamethasone was given to 3 patients for ICANS...Conclusions : Our findings build on previous evidence that tocilizumab may be effective as a preventative, rather than reactive, measure for patients treated with a bispecific antibody for RRMM. Larger randomized studies are needed to confirm and expand on our results."

Clinical • Cerebral Hemorrhage • CNS Disorders • Epilepsy • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases

Prescriber Preference in Treatment of Relapsed or Refractory Multiple Myeloma (MM) and Diffuse Large B-Cell Lymphoma (DLBCL) (ASH 2024) - "CAR-T was given by 73% MM providers & 66% DLBCL (92% used Cilta-cel, 96% used Ide-cel; 100% used Axi-cel, 90% used Liso-cel & 73% Tisa-cel)...Academic providers preferred Teclistamab (89% vs 50%), & nonacademic providers preferred Talquetamab (38% vs 4%) and Elranatamab (13% vs 8%).In DLBCL after 2+ LOT, 69% favored Axi-cel due to prior experience, RR, center choice, & logistical issues with other products...Epcoritamab was preferred by 56% (subcutaneous injection, more experience & center choice) & Glofitamab by 42% (shorter treatment duration, easy administration, more experience, & center choice)...Efforts to streamline referral pathways, logistics, & expanding availability are crucial to improve outcomes. Understanding these preferences & barriers can guide future management strategies."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Real-World Experience of Infections with T-Cell Engagers in Multiple Myeloma and Non-Hodgkin's Lymphoma (ASH 2024) - "TCEs included in the analysis include : teclistamab, elranatamab, talquetamab, mosunetuzumab, epcoritamab, and glofitamab. Interestingly, treatment delays did not seem to affect response rates. Given the high incidence of infections, it is essential to explore additional strategies to reduce infection rates."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cytomegalovirus Infection • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Herpes Simplex • Infectious Disease • Lymphoma • Multiple Myeloma • Nephrology • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases

Multiple Myeloma Persister Cells Surviving Bispecific Antibodies and CAR-T Cells Exhibit New CD45+ Expression (ASH 2024) - "Myeloma Drug Sensitivity Testing (My-DST) was performed as previously described using 1nM anti-BCMA bsAbs elranatamab and teclistamab, anti-GPRC5D talquetamab, and anti-CD38 SAR442257 (Walker et al, Blood Adv. Conclusion : These data support that (1) CD45 expression increases at the RNA and protein level on MM persisting after TCRT, (2) this is caused by a soluble factor secreted by stimulated T cells, and (3) LAG-3 may be a potential target for post-TCRT MM. The CD45+LAG-3+ phenotype aligns with previous reports of an immunosuppressive response cancer cells may use to provide protection from T cell attack."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CTCs • IL6 • LAG3 • PTPRC • SDC1

Comprehensive Review of Bispecific Antibody Constructs In Multiple Myeloma: Affinities, Dosing Strategies and Future Perspectives. (PubMed, Clin Lymphoma Myeloma Leuk) - "Teclistamab, elranatamab (both BCMA × CD3), and talquetamab (GPRC5D × CD3) are approved for treating MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody...As linvoseltamab, alnuctamab, and ABBV-383 (all BCMA × CD3), as well as forimtamig (GPRC5D × CD3) and cevostamab (FcRH5 × CD3) progress through late-stage clinical development, emerging trispecific antibodies are now available that target either 2 different MM-associated antigens or provide additional co-stimulatory signals to prevent T-cell exhaustion. Despite this plethora of therapeutic options, resistance to bsAbs is an inevitability, and the optimal positioning of these drugs within the current MM treatment landscape remains to be determined. In this review, we examine the available data on all clinically accessible bsAbs, evaluating their potential, current limitations, and..."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Depletion of Mature B Cells and of Normal Plasma Cells (PC) behind the Higher Incidence of Infections after Anti-BCMA VS Anti-GPRC5D Bispecific Antibodies (bsAb) in Relapsed Refractory Multiple Myeloma (RRMM) (ASH 2024) - "Background : BsAbs have become a standard part of therapy in RRMM with three approved agents targeting BCMA (teclistamab, elranatamab) and GPRC5D (talquetamab). These immune dynamics may explain the higher incidence of infections with anti-BCMA bsAb. These data, which can be collected simultaneously to MRD assessment, may potentially help in treatment individualization of RRMM patients to reduce the risk of severe infections."

IO biomarker • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • GPRC5D