cevostamab (RG6160) / Roche - LARVOL DELTA

Subcutaneous cevostamab demonstrates manageable safety and clinically meaningful activity in Relapsed/Refractory multiple myeloma (RRMM): First results from the Phase Ib CAMMA 3 study (ASH 2025) - "CRS primarily occurred in C1 and was mostly low Gr (Gr 1: 34.5%; Gr 2: 32.8%; Gr 3: 1.7%).Patients with CRS were frequently managed with tocilizumab (50.0%), steroids (67.5%), or both agents(32.5%); all events resolved. SC cevostamab monotherapy induces deep and durable responses and has manageablesafety in patients with late-line RRMM, many of whom had received prior BCMA-targeted therapies.Efficacy and safety (including CRS) appear generally comparable with that observed with IV cevostamabmonotherapy in patients with late-line RRMM, with the exception of the occurrence of low Gr ISRs."

Clinical • IO biomarker • P1 data • CNS Disorders • Dermatology • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Pruritus • Thrombocytopenia

Phase 2 study of cevostamab consolidation following BCMA CAR T cell therapy: preliminary safety, efficacy, and correlative data from the "STEM" (Sequential T Cell-Engagement for Myeloma) trial (ASH 2025) - P2 | "Median number of prior lines was 4 (2-10), with 74% triple-class refractory, 11% prior BCMA therapy, and 11% prior talquetamab. Twenty-five (93%) received cilta-cel and 2 (7%) ide-cel... To date, cevostamab consolidation starting 10-12 weeks post-CAR T cell infusion at 3.6mgsingle step-up and 132mg q3wk target dose appears feasible and well-tolerated in heavily-pretreatedRRMM, with low rates of non-hematologic G3/4 TEAE's, including infections. Preliminary efficacy appearspromising, with over 90% showing sustained MRD-negative CR at 1 year. Analyses and follow-up areongoing."

CAR T-Cell Therapy • Clinical • IO biomarker • P2 data • Ataxia • Autoimmune Hepatitis • Cough • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Musculoskeletal Pain • Neutropenia • Respiratory Diseases • Thrombocytopenia

Tumor intrinsic mechanisms leading to cevostamab resistance in multiple myeloma (ASH 2025) - "Allpatients had previously been treated with both immunomodulatory drugs (IMiDs) and proteasomeinhibitors (PI) and eight patients had received daratumumab prior to cevostamab, which was, on average,the 6th line of treatment (mean treatment duration 220±273 days). Due to thelimited sample size, these findings require validation in larger cohorts. Nonetheless, our findings begin toelucidate tumor intrinsic mechanisms associated with cevostamab resistance."

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

Tumor clearance, T-cell fitness, and minimal residual disease (MRD) outcomes in patients with relapsed/refractory multiple myeloma (RRMM) treated with cevostamab plus pomalidomide and dexamethasone: Biomarker analyses from CAMMA 1 Arm B (ASH 2025) - P1 | "Combination treatment is also associated with deep and durable declines insBCMA levels and high rates of CR+MRD-negativity. Updated biomarker data will be presented, includingbaseline immune fitness and correlation with MRD negativity."

Biomarker • Clinical • IO biomarker • Minimal residual disease • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • CD8

Cevostamab Consolidation After BCMA CAR T-Cell Therapy for Patients With R/R Multiple Myeloma: "STEM" Trial (HMPL Global) - "Getting to the efficacy data, 63% of patients were already incomplete response when they entered the trial post-CAR, that number went up to over 80% after 8 cycles. In the patients who are evaluable at the one year mark, so far, it's over 93% of patients in complete response. The 1 year MRD-negative CR rate is 93%."

P2 data • Multiple Myeloma

Endless possibilities and how to exploit them? What is the optimal treatment sequence? (PubMed, Hematology Am Soc Hematol Educ Program) - "For transplant-eligible, transplant-deferred, and fit transplant-ineligible patients who are younger than 80 years old, we use anti-CD38 mAb-, lenalidomide-, and bortezomib/carfilzomib-based quadruplets as an induction regimen. For early relapse (1-3 prior lines), chimeric antigen receptor T-cell therapies targeting B-cell maturation antigen (BCMA) have demonstrated superiority over standard regimens, with ciltacabtagene autoleucel (cilta-cel) being the most efficacious product currently, albeit with some unique toxicities such as parkinsomism...In late relapse (≥4 prior lines), bispecific antibodies (BsAbs) targeting BCMA (teclistamab, elranatamab, and linvoseltamab) and GPRC5D (talquetamab) have demonstrated impressive single-agent activity with distinct toxicity profiles...For patients with BCMA- and GPRC5D-refractory disease, FcRH5-targeting BsAb (cevostamab), BCL2 inhibitors for t(11;14)-positive disease, and novel trispecific antibodies (BCMAXCD38; BCMAXGPRC5D)..."

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

Initial results from the phase 1b CAMMA 3 study (EUDRACT: 2021-002307-36) shared during the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition showed that subcutaneous (SC) cevostamab achieved clinically meaningful activity in patients with relapsed/refractory multiple myeloma (Cancer Network) - "Of 52 efficacy-evaluable patients, the overall response rate (ORR) was 38.8% (95% CI, 24.1%–53.4%) across all tested dose levels. Further, the agent demonstrated a stringent complete response (sCR) in 14.3% of patients, complete response (CR) in 6.1%, very good partial response (VGPR) in 10.2%, and partial response in 8.2%. The median duration of response (DOR) was 12.3 months (95% CI, 8.3–not estimable). Notably, responses were particularly pronounced among those patients who were B-cell maturation antigen (BCMA) therapy-naive, achieving an ORR of 52.0% (95% CI, 30.4%–73.6%) vs 25.0% (95% CI, 5.6%–44.4%) among those who were BCMA-exposed (n = 26, each group)."

P1 data • Multiple Myeloma

Evaluation of Immune Reconstitution in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Cevostamab in Phase I Study GO39775 (ASH 2023) - P1 | "At data cut-off (March 1, 2023), a total of 310 patients were enrolled in GO39775. 76 patients met the inclusion criteria and were eligible for analysis. Median age was 65 years (range: 43–82), with a median of 6 previous lines of therapy (range: 2–12)."

Clinical • P1 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Tocilizumab Prophylaxis for Patients Treated with Teclistamab: A Single-Center Experience (ASH 2023) - "Emerging data from 28 RRMM patients treated with the bispecific antibody cevostamab (targeting FcRH5 and CD3) indicate that use of prophylactic tocilizumab, an anti-IL6 monoclonal antibody, can reduce the risk of developing CRS significantly, without impacting its anti-myeloma activity (Trudel et al. Our findings suggest that tocilizumab may be effective as a preventative, rather than reactive, measure for patients treated with teclistamab. Larger studies are needed to confirm and expand on our results."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma

High Dimensional Profiling of Patient-Derived Multiple Myeloma Bone Marrow Specimens Treated with an FcRH5-Targeted Bispecific Ex Vivo (ASH 2023) - P, P1 | "Background: Cevostamab is an FcRH5 (Fc receptor-homolog 5) targeted T cell-dependent bispecific (TDB) currently being evaluated in the clinic, with promising activity and favorable safety profile as a monotherapy in patients (pts) with heavily pre-treated Relapsed/Refractory multiple myeloma (MM) (NCT03275103, Trudel et al... We first examined the T cell compartment by scRNA-seq profiling. Upon FcRH5 TDB treatment, clustering analysis suggested that CD4 and CD8 T cells undergo extensive transcriptional changes compared to control TDB (Fig 1A). A TNF and LTA-expressing CD4 memory cluster was enriched upon treatment in both SoRs and Rs, but to a greater extent in Rs."

IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • CCND2 • CD38 • CD44 • CD8 • CXCL9 • HLA-E • IFNG • SDC1 • SOCS1 • SRGN • TNFSF10

Pooled Analysis on Bispecific Antibody-Related Toxicities in Multiple Myeloma (ASH 2023) - "BsAb included in our study were the following: Teclistamab, Elranatamab, REGN-5458, AMG420, AMG701, CC-93269, TNB-383B, Linvoseltamab, Talquetamab, and Cevostamab. The use of BsAbs in MM has demonstrated remarkable efficacy; however, these have been linked to a unique adverse event profile. Our results showed that non-BCMA bsAb were associated less hematotoxicity (combined grade 3-4 events and hypogammaglobulinemia), whereas BCMA bsAb were associated with less CRS rates. This is important information for treatment selection and mitigation strategy development aiming to optimize patient outcomes."

Retrospective data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

MODULE 4: Bispecific Antibodies in the Treatment of MM (ASH 2023) - "Supported by AbbVie Inc, GSK, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Karyopharm Therapeutics, Legend Biotech, Regeneron Pharmaceuticals Inc, and Sanofi. Similarities and differences in the cellular targets and mechanisms of action among bispecific antibodies for MM Antitumor activity observed with teclistamab in the Phase I/II MajesTEC-1 study leading to its recent FDA approval for R/R MM; optimal incorporation into the treatment paradigm Rate, depth and duration of response observed with elranatamab in the pivotal Phase II MagnetisMM-3 trial for patients with R/R MM; FDA approval and current clinical role Key findings with other promising anti-BCMA bispecific antibody constructions, such as alnuctamab, linvoseltamab and ABBV-383, for heavily pretreated MM Available efficacy and safety findings with non-BCMA-targeted bispecific antibodies for MM, such as talquetamab, cevostamab and RG6234; FDA approval of talquetamab for patients with R/R MM..."

Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mantle Cell Lymphoma • Oncology

Epigenetic Silencing of Immunotherapy Targets in Multiple Myeloma (DGHO 2025) - "Known genetic drivers: structural variants (SVs), deletions, single-nucleotide variants (SNVs) in target genes, only account for a minority of resistant cases, suggesting alternative mechanisms e.g. epigenetic ones.We performed long-read Nanopore sequencing on sequential bone marrow samples from patients who relapsed to anti-BCMA (CAR T, elranatamab, belantamab) and anti-FCRL5 therapies (cevostamab). Our findings advocate for the clinical integration of methylation profiling as a predictive and monitoring tool to anticipate resistance. The observations of an "epigenetic resistance memory" argues in favour of a broader, underappreciated role in multidrug resistance."

IO biomarker • Hematological Malignancies • Multiple Myeloma • CRBN • DNMT1 • DNMT3A • DNMT3B

MODULE 4: Bispecific Antibodies for the Treatment of MM (ASH 2024) - "This program is supported by educational grants from GSK, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC and Karyopharm Therapeutics.Available efficacy and safety findings leading to the FDA approvals of the BCMA-directed bispecific antibodies teclistamab and elranatamab for R/R MM; optimal incorporation into management algorithms Efficacy and safety documented with investigational anti-BCMA bispecific antibodies for pretreated MM, such as linvoseltamab and alnuctamab Available efficacy and safety findings with non-BCMA-targeted bispecific antibodies for MM, such as talquetamab and cevostamab Recent FDA approval and optimal incorporation of talquetamab into disease management Spectrum, incidence and severity of CRS and other toxicities with various BCMA- and non-BCMA-directed bispecific antibodies; optimal mitigation and management strategies Rationale for and early-phase data with bispecific antibodies in combination with other systemic therapies,..."

Hematological Malignancies • Multiple Myeloma • Oncology

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 • Plasma Cell Leukemia • Pneumonia • Respiratory Diseases

Epigenetic Modifications As a Mechanism of Resistance to BCMA-Directed Immunotherapies in Multiple Myeloma: Insights from Multi-Omic Profiling (ASH 2024) - "It benefits haplotype phasing, resolving complex repetitive regions and large complex SVs.MethodsWe analyzed pre- and post-treatment samples and PBMCs from three RRMM patients resistant to different BCMA-directed therapies (BCMA CART, elranatamab, and belantamab mafodotin)...In patient one, BCMA methylation increased by 53%, rising from 36% in the pre-CART to 89% in the post-CART sample (and 89% as well at a later relapse post-cevostamab)...The efficacy of demethylating agents to overcome drug resistance needs further investigation. Methylation marks can trace a cancer cell´s memory, reflecting its development and treatment history."

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

A Phase 2, Single-Arm, Non-Inferiority Study of Limited-Duration Teclistamab for Relapsed and Refractory Multiple Myeloma (LimiTec) (ASH 2023) - "Sustained off-drug responses have been observed in patients who discontinued teclistamab for reasons other than progression and have also been reported with cevostamab, an anti-FcRH5xCD3 bispecific antibody under investigation as a limited-duration regimen (17 cycles) in MM (Lesokhin et al, ASH 2022). This single-arm, phase 2 study is exploring whether limited-duration teclistamab is non-inferior to continuously administered therapy in patients who have received 6 to 9 months of teclistamab and have achieved at least a very good partial response. Accrual started in July 2023."

Head-to-Head • IO biomarker • P2 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Sequential T-Cell Engagement for Myeloma ("STEM") Trial: A Phase 2 Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy (ASH 2023) - P2 | "Background and significance: The BCMA-targeted CAR T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are currently approved for relapsed/refractory multiple myeloma (RRMM) patients with ≥4 prior lines of therapy, including an IMID, proteasome inhibitor, and CD38 antibody. This phase 2 study is exploring the efficacy, safety, and feasibility of cevostamab consolidation following BCMA-directed CAR T cell therapy for RRMM, with the goal of sequential T cell engagement against 2 different antigens to eliminate residual disease. Accrual started in July 2023."

CAR T-Cell Therapy • IO biomarker • P2 data • CNS Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Oncology • Parkinson's Disease • Rare Diseases

Integrative Analysis of the Tumor and Microenvironment to Model the Molecular Heterogeneity Underlying the Response to Cevostamab in Relapsed/Refractory Multiple Myeloma (ASH 2023) - P1 | "Patients who had less than 25% missingness in any data layer were selected from the single-step (3.6/90–252mg dose levels [n=49] and 3.6/90mg tocilizumab premedication group [n=14; Trudel et al. Our novel, unbiased, machine learning, integrative clustering approach not only revealed unique molecular subtypes that illustrate the heterogeneity of patients with RRMM, but also identified immunological features associated with potentially reduced response to cevostamab therapy, which could provide direction for future research."

Heterogeneity • Hematological Malignancies • Multiple Myeloma • Oncology

Quantitative Pharmacology for Dose and Regimen Determination of Cevostamab Monotherapy in Relapsed/Refractory Multiple Myeloma (ASH 2024) - P1 | "A comprehensive in silico evaluation based on QSP simulations indicated that the 0.3/1.2/3.6mg triple-step priming regimen prior to the target dose falls within the region of lowest post-dose peak IL-6 concentrations suggesting lowered CRS risk for cevostamab. The clinical data, along with the E-R and PopPK-TGI analyses, demonstrate that increasing cevostamab exposure is associated with higher response rates (overall response rate and VGPR+ rate), with the attainment of plateau at the 160mg Q3W dose, implying diminishing gains at doses beyond 160mg Q3W.Conclusions : The model-guided clinical dose escalation/expansion data together with the quantitative pharmacology strategies and insights support that the 0.3/1.2/3.6mg triple-step priming regimen and the Q3W 160mg target dose provides a favorable benefit-risk for the R/R MM population."

Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology • IL6

Novel PD-L1 Blocking Peptide with Mitochondrial Targeting Sequence: A Strategy to Counteract Resistance in T-Cell Immunotherapy for Myeloma (ASH 2024) - "We hypothesize that combining PP-k with T-cell-engagers will significantly enhance MM cell killing and overcome resistance.Objectives : We evaluated PP-k alone and together with teclistamab (approved BCMAxCD3 antibody) and cevostamab (FcRH5xCD3 antibody) in preclinical models of myeloma, including in vitro assays and an organ culture model where myeloma cells colonize the bone microenvironment. In the immune-suppressive tumor : bone co-cultures, PP-k significantly enhances T-cell activation when combined with bispecific antibodies. Ongoing studies with patient-derived cells and immunocompetent mouse models are investigating PP-k's efficacy, mechanism of action, and potential for future clinical trials."

Hematological Malignancies • Multiple Myeloma • Oncology • CALR • CD8 • GZMB • IL2RA

A Multi-Institution Phase 2, Single-Arm, Non-Inferiority Study of Limited-Duration Teclistamab for Relapsed and Refractory Multiple Myeloma (LimiTec) (ASH 2024) - P2 | "Sustained off-drug responses have been observed in patients who discontinued teclistamab for reasons other than progression and have also been reported with cevostamab, an anti-FcRH5xCD3 bispecific antibody under investigation as a limited-duration regimen (17 cycles) in MM (Lesokhin et al, ASH 2022). Conclusions : This multi-institution, single-arm, phase 2 study is exploring whether limited-duration teclistamab is non-inferior to continuously administered therapy in patients who have received 6 to 9 months of teclistamab and have achieved at least a very good partial response. Accrual started in July 2023 and is ongoing."

Clinical • Head-to-Head • IO biomarker • P2 data • Hematological Malignancies • Infectious Disease • Leukemia • Multiple Myeloma • Oncology

Biomarker Correlates and Clinical Activity of Cevostamab in Patients (pts) with Triple-Class Refractory Multiple Myeloma (MM) Who Have Received ≥1 Prior B-Cell Maturation Antigen (BCMA)-Targeted Bispecific Antibody (BsAb): Results from the Phase I/II CAMMA 2 Study (ASH 2024) - P1/2 | "Clinical responses were less frequent in the prior BsAb group than in the prior ADC and CAR-T groups, which could be explained by the higher number of prior lines of therapy and T-cell exhaustion due to multiple prior exposures to BsAbs. Notably, the high frequency of CD8+ T-cell subsets expressing inhibitory immune checkpoints in the prior BsAb group suggests a level of T-cell dysfunction that could prevent effective T-cell activation."

Biomarker • Clinical • IO biomarker • P1/2 data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • CD8 • IFNG • IL6 • PD-1 • TIGIT

Remote Patient Monitoring for Early Detection of Cytokine Release Syndrome in Myeloma Patients: A Comparative Study between Standard Care and Remote Monitoring (ASH 2024) - "Material and Methods : This monocentric academic study included patients with RRMM treated with a bsAb (teclistamab, talquetamab, cevostamab). These findings offer opportunities for safe and controlled RPM use in an outpatient setting after bsAb administration. In addition, our observations endorse further investigation into the RPM system, particularly on the added value of more comprehensive measurements to the temperature only assessment for early CRS detection."

Clinical • Cytokine release syndrome • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

Cevostamab in Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study Demonstrate Clinically Meaningful Activity and Manageable Safety and Inform the Doses and Regimen for Combination Studies (ASH 2024) - P1 | "Pts with CRS were managed with tocilizumab (47.4%), steroids (21.1%), or both agents (10.5%). C1 TS dosing provides effective CRS mitigation. Cevostamab combination studies may use the 0.3/1.2/3.6mg TS regimen and the Q3W 160mg TD (or similar TD exposure)."

Clinical • P1 data • Anemia • Cough • Fatigue • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Rare Diseases • Respiratory Diseases • Septic Shock