In a multinational Phase 3 study of about 900 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), a treatment strategy that combined Monjuvi (tafasitamab) with Bristol Myers Squibb’s Revlimid and the standard R-CHOP chemotherapy regimen cut the risk of disease progression, relapse or death by 25% compared with R-CHOP alone.
The data, first disclosed in January and presented in more detail at the American Society of Clinical Oncology meeting in Chicago, show a meaningful reduction in the trial’s primary composite endpoint but come with a higher burden of toxicity. The company said overall survival information for the combination will be provided at a later date.
Pablo Cagnoni, the company’s head of research, described the survival analysis as "early" yet indicative of a trend toward improvement. He emphasized that survival outcomes are the key integrating metric for weighing added efficacy against increased toxicity, noting that adding a drug to an existing regimen often brings more side effects.
The randomized study compared a multi-drug approach - Monjuvi plus Revlimid together with R-CHOP - against R-CHOP alone in patients newly diagnosed with DLBCL, the most common form of non-Hodgkin lymphoma. The trial enrolled approximately 900 patients.
Safety results showed the intensified regimen had a higher frequency of severe adverse events, reported in nearly 87% of patients who received the Monjuvi-containing combination versus 76% of those treated with R-CHOP alone. Treatment discontinuations attributed to adverse events were also elevated at 25.7% for the combination arm, compared with 18% in the standard-care arm.
Deaths listed as due to adverse events occurred in 6% of patients on the Monjuvi combo, compared with 3.8% in the R-CHOP-only group. Despite those figures, the overall death rate was lower for the three-drug arm at 18.5%, compared with 21.7% for R-CHOP.
Company leaders expect that, if regulators approve the expanded indication, more than half of the high-risk patient population that still receives R-CHOP today could be eligible to receive the combination as a first-line treatment. Incyte said it plans to seek expanded approval in the United States and in Europe to make the regimen available as an initial therapy for newly diagnosed patients.
Monjuvi, chemically tafasitamab, is already cleared in the United States under accelerated approval when used with Revlimid for patients whose disease has returned or who did not respond to prior therapy and who are not candidates for stem cell transplant. The company aims to broaden the drug’s labeled use to an earlier-stage, first-line setting pending regulatory review.
DLBCL affects an estimated 18,000 to 25,000 people in the United States each year, according to government figures cited by the company.
Presentation and timing notes: the trial outcome regarding the composite endpoint was revealed previously in January, and the full dataset and more granular safety and discontinuation details were reviewed publicly at the ASCO meeting in Chicago. Company executives reiterated that final overall survival data will be forthcoming and are critical to determining the regimen’s net clinical benefit.
The tension between improved disease control and higher toxicity underscores the challenges of adding targeted or immunologic agents to cytotoxic chemotherapy backbones. Regulators, clinicians and patients will weigh the incremental reduction in progression, relapse or death against the higher rate of severe adverse events and a measurable rise in treatment discontinuations when assessing the regimen’s role in first-line care.