Columvi (glofitamab-gxbm) / Roche, Biogen - LARVOL DELTA

From Molecular Precision to Clinical Practice: A Comprehensive Review of Bispecific and Trispecific Antibodies in Hematologic Malignancies. (PubMed, Int J Mol Sci) - "Clinical trials of agents like blinatumomab, glofitamab, mosunetuzumab, and teclistamab have demonstrated deep and durable responses in heavily pretreated populations. Finally, we highlight the transformative role of artificial intelligence (AI) and machine learning (ML) in multispecific antibody development, including antigen discovery, biomarker-driven treatment selection, toxicity prediction, and therapeutic optimization. Together, BsAbs and TsAbs illustrate the convergence of molecular precision, clinical innovation, and AI-driven personalization, establishing a new paradigm for immune-based therapy across hematologic and potentially solid tumor malignancies."

IO biomarker • Journal • Review • Acute Lymphocytic Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

COMBINING BISPECIFICS AND RADIATION FOR REL/REF HEMATOLOGIC MALIGNANCIES: FRIEND OR FOE? (ICML 2025) - "BsAbs administered for LBCL were glofitamab (n = 5) and epcoritamab (n = 2), while those for MM included elranatamab (n = 10), teclistamab (n = 5), and talquetamab (n = 4). We report our early experience using RT in combination with BsAbs, highlighting its safety, feasibility, and excellent local control rates, even in bulky sites. Longer follow-up with larger cohorts is needed to assess the durability of response and the dose-response relationship."

B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

BRIDGING TO CAR-T CELL THERAPY IN LARGE B-CELL LYMPHOMA WITH EITHER CONVENTIONAL THERAPY OR THE CD3xCD20 BISPECIFIC ANTIBODY GLOFITAMAB (ICML 2025) - "NoGLO-treatment consisted of rituximab-based immunochemotherapy (12/23, 52%), tafasitamab-lenalidomide (6/23, 26%), high dose melphalan (3/23, 13%), or ibrutinib (2/23, 9%). Despite small sample size and limited follow-up, our data suggest glofitamab as an effective and safe bridging prior to CAR-T cell therapy, potentially superior to conventional approaches. Data on molecular immune effects will be presented at the conference."

CAR T-Cell Therapy • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ADVANCING NURSING KNOWLEDGE OF CD20-CD3 BISPECIFIC ANTIBODY TREATMENT FOR B-CELL NON-HODGKIN LYMPHOMA IN AUSTRALIA: A SCOPING REVIEW OF ADVERSE EVENTS TO INFORM PRACTICE (ICML 2025) - "Six BsAbs were identified: epcoritamab, glofitamab, imvotamab, mosunetuzumab, odronextamab and plamotamab...Supportive management, tocilizumab and corticosteroids were used for the treatment of CRS... BsAbs represent an effective treatment option in B-NHL with a unique side-effect profile. Some agents are now available through compassionate access programs in Australia and are increasingly encountered in routine practice around the world. This is the first published scoping review to synthesize evidence from clinical trials of BsAbs for nursing practice, informing nurses of the most common AEs and nursing led interventions for safe delivery and informed the development of an education package."

Adverse events • Review • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

GLOFITAMAB PLUS GEMCITABINE AND OXALIPLATIN (Glofit-GemOx) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): 2-YEAR FOLLOW-UP OF STARGLO (ICML 2025) - P3 | "In the Phase 3 STARGLO trial, Glofit-GemOx demonstrated overall survival (OS) and progression-free survival (PFS) benefits over rituximab (R)-GemOx in autologous stem cell transplant (ASCT)-ineligible R/R DLBCL (Abramson et al...After obinutuzumab pretreatment, glofitamab was given in Cycle (C) 1 as weekly step-up doses (2.5/10 mg) then 30 mg target dose every 21 days from C2 Day 1... With 2 yrs of follow-up, Glofit-GemOx sustained a clinically meaningful benefit in OS and PFS versus R-GemOx in ASCT-ineligible pts with R/R DLBCL, with most (82%) pts in CR at EOT still in remission. The safety profile was consistent with known risks of each drug. The updated analyses demonstrate durable remissions and maintained OS benefit in pts with R/R DLBCL treated with fixed duration Glofit-GemOx."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

A MULTICENTER PHASE II STUDY OF GLOFITAMAB PLUS POLATUZUMAB-R-CHP FOR PATIENTS WITH HIGH-RISK DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - P2 | "Funded by Genentech/Roche Background: While polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) resulted in improved outcomes for patients (pts) with newly diagnosed DLBCL as compared to R-CHOP (Tilly et al. Glofit-pola-R-CHP resulted in a high CR rate meeting the prespecified primary endpoint in pts with newly diagnosed DLBCL, and without new safety signals. When glofit was added after C2 of chemoimmunotherapy, CRS was uncommon and low grade. Further evaluation of this regimen is warranted."

Clinical • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

R-POLA-GLO – CHEMO-LIGHT FRONTLINE THERAPY INDUCES HIGH RESPONSE RATES WITH A FAVORABLE SAFETY PROFILE IN ELDERLY/FRAIL PATIENTS WITH AGGRESSIVE LYMPHOMA (ICML 2025) - "The need for effective therapies for pts with limited organ reserve led us to develop R-Pola-Glo as a first-line treatment for pts ineligible for full-dose R-CHOP, combining the anti-CD20 antibody rituximab (R), the antibody-drug conjugate polatuzumab vedotin (anti-CD79b, Pola) and the bispecific antibody glofitamab (CD20 × CD3, Glo)...Cycle 1 includes obinutuzumab, Pola, and Glo with step-up dosing (2.5 mg and 10 mg); cycles 2–6 include R, Pola, and Glo (30 mg), followed by 6 Glo consolidation cycles (30 mg)... R-Pola-Glo demonstrates high CMR rates with manageable safety, supporting further clinical investigation as a first-line treatment option for elderly/frail and medically unfit pts with aggressive lymphoma. * Equal contributions"

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD79B

PATIENT-DERIVED LYMPHOMA SPHEROIDS AS PRECLINICAL MODELS FOR PREDICTING PATIENT RESPONSES TO ADVANCED THERAPIES IN B-NHL: EXAMPLE OF GLOFITAMAB IN FOLLICULAR LYMPHOMA (ICML 2025) - "Our study shows that FL patients with high levels of functional CD4+ Tfh cells may have a reduced response to glofitamab due to their support of cancerous B-cells. Further research is needed to understand their role in glofitamab resistance and explore therapeutic options with BsAb and CD4 Tfh targeting. Additionally, our study validates the use of PDLS as preclinical models for exploring IE mechanisms and identify biomarkers of response to immunotherapy as shown by our teams (Faria C J Immunother Cancer 2023, Dobano-Lopez Blood Adv 2024)."

IO biomarker • Metastases • Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • CD8 • CXCL13 • CXCR5 • GNLY • GZMB • HAVCR2 • IFNG • IL21 • IL6 • LAG3 • PD-1 • PRF1 • TIGIT

INITIAL RESULTS FROM LOTIS-7: A PHASE 1B STUDY OF LONCASTUXIMAB TESIRINE PLUS GLOFITAMAB IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) (ICML 2025) - P1 | "Lonca+Glofit in R/R B-NHL showed a manageable safety profile consistent with each drug and encouraging efficacy in heavily pretreated aggressive lymphoma pts. Lonca+Glofit induced T-cell margination, and sustained circulating CD4+ and CD8+ T-cell activation was noted. Results support that Lonca complements Glofit's mechanism and provides additive efficacy."

Clinical • IO biomarker • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4 • CD8 • IL6

Outcomes of Glofitamab and Epcoritamab in R/R DLBCL elderly patients: A Real-World Evidence Study from the CUBIC Consortium (ICML 2025) - No abstract available

Clinical • HEOR • Real-world • Real-world evidence • Diffuse Large B Cell Lymphoma • Lymphoma • Oncology

CIRCULATING TUMOR DNA (ctDNA) FOR RESPONSE PREDICTION AND GENETIC CHARACTERIZATION OF RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (R/R LBCL) RECEIVING GLOFITAMAB TREATMENT (ICML 2025) - P1/2 | "Additionally, mutational analysis allows to deeply characterize the cohort's genetic profile and further investigate the mechanisms of resistance to Glofitamab. Despite the limited sample size, these findings highlight the potential role of ctDNA in disease monitoring and optimization of risk stratification in R/R LBCL patients."

Circulating tumor DNA • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • TP53

GLOFITAMAB+R-CHOP IN PATIENTS WITH PREVIOUSLY UNTREATED LARGE B-CELL LYMPHOMA DEFINED AS HIGH RISK BY CIRCULATING TUMOR DNA (ctDNA) DYNAMICS: PRIMARY RESULTS (ICML 2025) - P2 | "Dynamic on-treatment risk assessment using ctDNA offers the potential to identify high-risk pts with LBCL. 1L Glofit+R-CHOP induced high response rates with a manageable safety profile at EOT in pts with high-risk (by ctDNA) LBCL."

Circulating tumor DNA • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Glofitamab plus R-ICE or as monotherapy in children and adolescents with relapsed/refractory B-cell non-Hodgkin lymphoma: updated analysis from the iMATRIX-GLO study (ICML 2025) - No abstract available

Clinical • Monotherapy • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

RAPID STEP-UP DOSING SCHEDULE OF GLOFITAMAB IS SAFE AND EFFICACIOUS IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA (ICML 2025) - "Following a single 1000 mg dose of obinutuzumab on Cycle 1 Day 1 to deplete circulating and lymphoid tissue B cells, glofitamab is administered by intravenous infusion according to a step-up dosing schedule (2.5 mg on Day 8 of Cycle 1 and 10 mg on Day 15 of Cycle 1), then 30 mg on Day 1 of each subsequent cycle for a maximum of 12 cycles...One patient complained the whole-body bone pain, which was correlated with rapid disease progression, confirmed by CT scan, and this adverse event was recovered after use of denosumab... Glofitamab given with a rapid step-up dosing schedule was safe and efficacious in patients with relapsed/refractory DLBCL. The efficacy and safety profiles of this rapid step-up schedule needs to be verified in prospective clinical trials."

Clinical • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Secondary Central Nervous System Lymphoma • CD20

GLOFITAMAB MONOTHERAPY IN CHINESE PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: FINAL ANALYSIS OF A PHASE I TRIAL (ICML 2025) - P1 | "Pts received intravenous (IV) obinutuzumab pretreatment (Gpt; 1000 mg) on Cycle (C) 1 Day (D) 1, step-up glofitamab IV doses on C1D8 (2.5 mg) and C1D15 (10 mg), and the 30 mg target dose on D1 of C2–12 (21-day cycles). With extended follow-up, glofitamab monotherapy continues to show impressive response rates and long-lasting benefits in Chinese pts with R/R DLBCL after ≥ 2 prior therapies. Glofitamab was well tolerated with a manageable safety profile and no new safety concerns identified."

Clinical • Monotherapy • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

RAPID RAMP-UP DOSING OF BI-SPECIFIC ANTIBODIES IN RELAPSED OR REFRACTORY LARGE B-CELL LYMPHOMA (ICML 2025) - "26 patients received epcoritamab and 12 received glofitamab (11 received pre-dose obinutuzumab, 2–6 [median 3] days prior). BsAb rapid ramp-up appears feasible in patients with R/R LBCL, with similar CRS and ICANS rates and treatment responses compared to other real-world datasets. Keyword: aggressive B-cell non-Hodgkin lymphoma"

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

COMPARISON OF MORTALITY AND DISEASE PROGRESSION BETWEEN CHIMERIC ANTIGEN RECEPTOR T-CELL AND BISPECIFIC T-CELL ENGAGER USING THE FDA ADVERSE EVENT REPORTING SYSTEM (ICML 2025) - "Utilizing the publicly available FDA Adverse Event Reporting System (FAERS) we evaluated toxicities and outcomes of patients treated with lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), or epcoritamab and glofitamab therapies, between January 2022 and December 2024. While there are limitations of using FAERS that restrict the conclusion of causality due to reporting bias, this data demonstrates there are important toxicities that can inform treatment team's decisions. Further comparison of post-market data to existing randomized control trials will help further identify new adverse events, or elucidate existing under- or over-reported events."

Adverse events • CAR T-Cell Therapy • B Cell Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • ROR1

GLOFITAMAB AND EPCORITAMAB FOR LARGE B CELL LYMPHOMA IN 319 REAL WORLD PATIENTS: A RETROSPECTIVE UK ANALYSIS OF EFFICACY, TOLERABILITY AND PRACTICAL IMPLICATIONS (ICML 2025) - "14% (n = 45) of pts required tocilizumab and there was 1 CRS associated death. BsAbs achieved CMR in 22% (95% CI: 18–28) of pts who were high risk and highly refractory. Responses appear durable in those attaining CR in this heavily treated cohort and rates of CRS and ICANS were similar to trial data. Groups were not matched with differences in baseline characteristics, therefore this data does not serve as a comparison."

Real-world • Real-world evidence • Retrospective data • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Secondary Central Nervous System Lymphoma

BISPECIFIC ANTIBODIES AS HOLDING OR BRIDGING THERAPY BEFORE CAR-T IN LARGE B-CELL LYMPHOMA (ICML 2025) - "Of these, 20 patients received glofitamab as bridging therapy (2/20 received glofitamab as holding therapy as well), and 3 patients received epcoritamab as bridging therapy after a median of 2 treatment lines before bridging therapy...Furthermore, 7 patients were treated in the ICU after CAR-T therapy and 8 patients received tocilizumab after CAR-T therapy. With the limitations of a small sample size and short follow-up, our data suggest that bridging therapy with bABs before CAR-T therapy is safe and effective. More detailed data in a larger group of patients with sufficient follow-up time will be presented at the conference."

B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CANADIAN CANCER TRIALS GROUP LY.18: A PHASE I MASTER PROTOCOL OF NOVEL COMBINATION THERAPY FOR PATIENTS WITH RELAPSED/REFRACTORY LYMPHOMA—THE R-GDP-GLOFITAMAB SUBSTUDY (ICML 2025) - "Introduction: Second-line (2L) rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) followed by autologous stem cell transplantation (ASCT) is a standard of care in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Glofitamab in combination with R-GDP is safe and feasible prior to ASCT, with a low rate of CRS and expected rates of other toxicities. The addition of glofitamab to R-GDP is associated with very high response rates, although additional studies are necessary to better understand its role in curative 2L treatment, where consolidation approaches such as ASCT or CAR-T therapy may be used."

Clinical • Combination therapy • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

TIME TOXICITY IN THE ERA OF BISPECIFIC ANTIBODY TREATMENT IN RELAPSED/REFRACTORY NON-HODGKIN LYMPHOMA: CONCEPT ELICITATION WITH HEMATOLOGISTS AND PATIENT PERSPECTIVES (ICML 2025) - "Introduction: The treatment (tx) landscape for relapsed/refractory non-Hodgkin lymphoma (R/R NHL) has evolved with the approval of new tx options in the United States (US), including CD20xCD3 T-cell-engaging bispecific antibodies (BsAbs): mosunetuzumab, glofitamab, and epcoritamab. This was the first study to elicit the concept and importance of time toxicity in the era of BsAb tx for pts with R/R NHL. Pts, disease, BsAb tx, and visit factors are key considerations when assessing time toxicity of BsAb tx. Follow-up research is ongoing to engage more pts with R/R NHL and elucidate potential differences in time toxicity associated with various BsAbs, given the differences in tx duration and dosing frequency; these insights may help facilitate shared decision-making for patient-centric treatment choices, extending beyond considerations of efficacy and safety."

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

REAL-WORLD OUTCOMES OF CD20xCD3 BISPECIFIC ANTIBODY THERAPY IN ADULT PATIENTS WITH RELAPSED/REFRACTORY TRANSFORMED INDOLENT LYMPHOMA (ICML 2025) - "The study included adults (≥ 18 years old) with R/R tiNHL treated with CD20xCD3 BsAbs (Epcoritamab or Glofitamab), outside of clinical trials. In conclusion, our study is the first to specifically address the effectiveness of BsAbs in real-world for R/R tiNHL. Although the results appear lower than those seen in clinical trials, they suggest, acknowledging the limited sample size and follow-up, that this treatment modality could provide an important salvage option in this challenging-to-treat population."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Oncology

POLATUZUMAB VEDOTIN AND GLOFITAMAB: A SYNERGISTIC APPROACH TO ANTI-TUMOR ACTIVITY (ICML 2025) - "All groups received obinutuzumab pretreatment (30 mg/kg). Glofit plus Pola combination had synergistic anti-tumor efficacy, particularly in models where glofit-mediated T cell engagement might be suboptimal due to low and heterogeneous CD20 expression. The better tolerability of the combination was likely due to normal B cell and tumor cell de-bulking mediated by Pola, which mitigates the cytokine release associated with the first Glofit infusion. The observed increase in CD20 antigen expression in tumors treated with Pola likely plays an important role in enhancing Glofit activity and potentially overcoming tumor escape mechanisms related to CD20 antigen loss."

Lymphoma • Oncology • CD20 • CD4 • CD79B • CD8

A PROSPECTIVE ANALYSIS OF THE SAFETY AND EFFICACY OF PROPHYLACTIC DEXAMETHASONE FOR GLOFITAMAB ADMINISTRATION IN RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (ICML 2025) - "Institutional BsAb CRS/ICANS guidelines prioritized outpatient management and steroids for grade 1 CRS when appropriate, reserving tocilizumab for prolonged grade 2 or grade 3+ CRS. The study met the primary endpoint of a reduction in CRS rate with prophylactic dexamethasone and demonstrated low CRS/ICANS rates in a real-world r/r LBCL cohort. Response rates were consistent with the pivotal trial. These data support ongoing use of prophylactic dexamethasone with glofitamab and can help identify low risk pts appropriate for entirely outpatient administration with prophylactic dexamethasone support."

Clinical • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

OPTIMIZING FRONTLINE THERAPY FOR DIFFUSE LARGE B CELL LYMPHOMA IN OLDER ADULTS: A GLOfitamab-BASED, RESPONSE-ADAPTED, WINDOW-StYle STUDY (GLORY) (ICML 2025) - "The GLORY study is a window-style, glofitamab-based, response-adapted study with polatuzumab-rituximab-mini-CHP (pola-R-mini-CHP) backbone, specifically designed for unfit and frail OA with DLBCL undergoing treatment with curative intent. This is a single-stage design, and the study will be considered positive if 23 of 42 patients achieve a CR at the end of therapy. Additionally, the coprimary endpoint of CR rate after 2 cycles of glofit-pola will be used to stop for futility."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology