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The addition of polatuzumab vedotin-piiq (Polivy) to glofitamab-gxbm (Columvi) displayed durable responses and efficacy among patients with relapsed/refractory large B-cell lymphoma (LBCL) and patients with high-grade BCL (HGBCL), according to findings from a phase 1b/2 study (NCT03533283) published in the Journal of Clinical Oncology.1
Efficacy data from the trial revealed that after a median follow-up of 32.7 months (range, 0-55) for the total population (n = 129), the objective response rate (ORR) as assessed by an independent review committee (IRC) was 78.3%, with 59.7% attaining a complete response (CR). Additionally, similar results were found with the investigator-assessed ORR and CR rate, at 84.2% and 61.4%, respectively. Furthermore, after a median follow-up of 19.2 months (range, 0-43) among patients with HGBCL (n = 44), the ORR and CR rate was 79.5% and 65.9%.
Across all patients, the median duration of response (DOR) was 26.4 months (95% CI, 10.9-44.3), with a 24-month rate of 51.9%. For the 77 patients who attained a CR, the median duration of CR (DOCR) was 37.8 months (95% CI, 24.1-not estimable [NE]) after a median follow up of 25.5 months (range, 0-48), with a 24-month rate of 63.9%. Among patients with HGBCL, the median DOCR was not reached.
Additionally, the median progression-free survival (PFS) per IRC assessment was 12.3 months (95% CI, 8.8-27.7) for the overall population and 16.3 months (95% CI, 9.1-NE) for those with HGBCL. The 24-month PFS rate in the overall population was 41.8%. Additionally, the median overall survival (OS) and event-free survival (EFS) in the overall population was 33.8 months (95% CI, 20.6-NE) and 11.5 months (95% CI, 8.5-17.7), respectively; the OS data were immature at the clinical cutoff date, with a 24-month OS rate of 54.3%.
“[Glofitamab/polatuzumab vedotin] demonstrated high efficacy, with frequent and durable responses in patients with heavily pretreated [relapsed/refractory] LBCL, spanning various histologies and including individuals who received previous CAR T-cell therapy,” lead study author Martin Hutchings, MD, PhD, staff specialist in the Department of Hematology at the Finsen Centre, National Hospital, Copenhagen University Hospital in Denmark, wrote in the publication with study coinvestigators. “A particularly important finding was the high activity in patients with HGBCL. The safety profile remained manageable. Long-term follow-up data on [glofitamab/polatuzumab vedotin] in patients with [relapsed/refractory] LBCL, including HGBCL, will offer valuable insights into its promising potential as a therapeutic option for patients with [relapsed/refractory] LBCL.”
The open-label phase 1b/2 trial enrolled patients with relapsed/refractory LBCL, including diffuse large B-cell lymphoma (DLBCL), HGBCL, transformed follicular lymphoma, and primary mediastinal LBCL. The study was expanded to include 44 patients with HGBCL based on a high unmet need in this subgroup.
Patients received pretreatment with 1000 mg of obinutuzumab (Gazyva) on cycle 1, day 1 at 7 days prior to the first glofitamab dose to help mitigate the frequency of cytokine release syndrome (CRS). Polatuzumab vedotin was given intravenously at 1.8 mg/kg on cycle 1, day 2 and day 1 of cycles 2 to 6 once daily for each 21-day cycle. Intravenous glofitamab was given as step-up dosing during cycle 1, at 2.5 mg on day 8 and 10 mg on day 15; the target dose of 30 mg was given on day 1 of cycles 2 to 12 for each 21-day cycle.
Following the first glofitamab dose, patients were hospitalized for 24 hours. A fixed duration of 6 cycles for polatuzumab vedotin and 12 cycles for glofitamab was given in the absence of disease progression, unacceptable toxicities, or withdrawal of consent. Patients with responses or stable disease were followed until disease progression, and those with progressive disease were followed for survival after an end-of-study visit.
Among the overall and HGBCL populations, the median age was 67.0 years (range, 23-84) and 66.5 years (range, 24-84). Most patients were male (63.6% vs 63.6%), had an ECOG performance status of 0 or 1 (94.6% vs 93.2%), and had Ann Arbor stage III/IV disease (76.7% vs 72.7%). Patients most often had an Internal Prognostic Index (IPI) score of 2 (30.2% vs 29.5%), 3 (24.0% vs 20.5%), and 4 (23.3% vs 25.0%).
A total of 72.9% vs 70.5% of the overall and HGBCL groups had extranodal involvement at study start, and 29.5% vs 22.7% had bulky disease. Most patients were negative for double- or triple-hit lymphoma (45.7% vs 27.3%), had received 2 or more lines of treatment (58.9% vs 45.5%), and were refractory to the first line of previous therapy (62.0% vs 70.5%) or any previous therapy (79.1% vs 81.8%).
The primary end point of the trial was IRC-assessed ORR per PET-CT scan per Lugano 2014 criteria. Secondary end points included investigator-assessed ORR, DOR, DOCR, PFS, EFS, OS, and safety.
Regarding safety, 99.2% of patients experienced any-grade adverse effects (AEs), the most common of which were CRS (43.4%), neutropenia (41.9%), peripheral neuropathy (26.4%), diarrhea (24.0%), COVID-19 infection (23.3%), and pyrexia (20.2%). Additionally, 58.9% of patients experienced grade 3 or 4 AEs; the most common included neutropenia (32.6%), COVID-19 infection or pneumonia (9.4%), anemia (8.5%), thrombocytopenia (8.5%), and tumor flare (7.0%). Grade 5 AEs occurred in 9.3% of patients, and serious AEs occurred in 61.2%.
AEs led to discontinuation in 14.7% of patients, including 12.4% discontinuing glofitamab and 8.5% discontinuing polatuzumab vedotin. Only 1 instance of grade 3 and grade 5 CRS was observed, with serious CRS occurring in 29.4% of patients.
The time to CRS onset after the 30 mg once daily dose was 36.2 hours (range, 18.5-55.9). The most common CRS management strategies included tocilizumab (Actemra; 33.9%), intravenous fluids (23.2%), low-flow oxygen (19.6%), and corticosteroids (14.3%).
Reference
Hutchings M, Sureda A, Bosch F, et al. Efficacy and safety of glofitamab plus polatuzumab vedotin in relapsed/refractory large B-cell lymphoma including high-grade B-cell lymphoma: results from a phase Ib/II trial. J Clin Oncol. Published October 20, 2025. doi:10.1200/JCO-25-00992
The boss of the US private equity group bidding for the Daily Telegraph has been reported to the UK government for potentially breaching rules protecting the newspaper’s editorial independence, after allegedly threatening to “go to war” with the title’s newsroom.
The Guardian understands that the independent directors of Telegraph Media Group (TMG) have alerted the Department for Culture, Media and Sport (DCMS) about supposed comments made by RedBird Capital’s Gerry Cardinale to the Telegraph’s editor, Chris Evans. The government department is thought to be considering if there has been a breach of the legislation.
The title’s former editor Charles Moore disclosed in his Telegraph column last month that inquiries by the paper’s journalists into RedBird Capital’s bid had prompted Cardinale to “threaten he would go to war with our entire newsroom”.
Moore added there had been “apparent media briefings” that Evans would be removed and replaced as editor – although that was followed up by a column the Telegraph published by Cardinale last week.
In it, the private equity boss said: “We won’t ever compromise the editorial independence of the Telegraph. At RedBird, we are very clear about one fundamental premise: don’t invest in a newspaper if you want to influence it – that will kill the investment thesis and is just bad business.”
Last year the government introduced a statutory instrument compelling parties to “take all reasonable steps to retain key staff within the Telegraph Media Group business and to ensure that no key staff are removed from their position”.
The order added: “At all times, the … acquiring entities must keep the secretary of state informed of any material developments relating to the Telegraph Media Group business, which includes details of key staff who leave or join the Telegraph Media Group business.”
The referral to the culture department follows yet another eventful few weeks in the saga of the acquisition of the Telegraph, which has come under scrutiny as the initial acquisition was funded by foreign state interests. Last week the newspaper linked its presumed new owner to the suspected ringleader of the alleged Chinese spy ring in Westminster.
The Telegraph’s future has been uncertain since the Barclay family lost its grip on the media group in 2023 in a row about unpaid debts. An organisation connected to Redbird Capital, called Redbird IMI, took control of the newspaper titles later that year.
However, RedBird IMI was forced to put the papers up for sale in spring 2024 after the then Conservative government passed a law blocking foreign states or associated individuals from owning newspaper assets in the UK. Redbird IMI is in the process of selling TMG to RedBird Capital – which holds various investments, including a stake in the parent company of Liverpool football club.
While a quarter of RedBird IMI’s funding came from RedBird Capital, the remainder was sourced from International Media Investments (IMI), which is controlled by Abu Dhabi’s Sheikh Mansour bin Zayed al-Nahyan, the vice-president of the United Arab Emirates and owner of Manchester City FC.
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The Labour government eased the ban on foreign governments owning stakes in UK newspapers this year by allowing them to hold up to 15% of titles, ultimately allowing the RedBird Capital offer that would include IMI retaining a 15% Telegraph stake.
The DCMS and a spokesperson for TMG’s directors declined to comment on the report to DCMS by the Telegraph’s directors.
A spokesperson for RedBird Capital said: “RedBird is a private equity fund, not a proprietor, and the mandate of the fund is to grow the value of its investments. The way to grow the value of the Telegraph is to grow subscribers and the way to do that is to embrace and support the values that matter most to subscribers – namely, free speech and independent journalism.
“As such, we have committed to establishing an independent advisory board tasked with upholding the highest standards of journalistic integrity. The deputy chairman of the Telegraph Media Group, Lord Black, has agreed to design its framework.”
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Appendix 1 presents a scheme for the equations used in the model: a Hodgkin–Huxley type equation with seven intrinsic currents, Ca2+ sensors, and an activity-dependent regulation mechanism.
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