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Several phase II studies have reported encouraging responses to bispecific antibody treatments, alone or in combinations, for older or unfit people with newly diagnosed diffuse large B-cell lymphoma. The results are promising but come from studies with limited follow-up; infections, treatment tolerability and whether remissions last remain concerns.
Phase II studies of bispecific antibody treatments have reported high response rates among older or unfit patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), MedPage Today reported. The findings point to possible treatment options for patients who may not tolerate full-dose chemotherapy, but researchers say longer follow-up and better ways to manage infections are needed.
One prospective phase II study combined glofitamab, rituximab and polatuzumab vedotin in previously untreated patients who were elderly or considered unfit or frail. Participants had a median age of 80, and 19% were older than 85. Overall response rates ranged from 90% to 96% across treatment cycles; one-year progression-free survival was 85% and overall survival was 90%. These are results from a single study, not a comparison with another regimen.
A separate phase II trial led by Dai Chihara, MD, PhD, assessed epcoritamab with rituximab and reduced-dose chemotherapy in older, unfit or frail patients, as well as patients unable to receive anthracyclines. It reported an 86% complete response rate and 94.7% one-year progression-free survival. Two phase II studies of bispecific antibody monotherapy also reported responses: epcoritamab produced a 70% overall response rate and 58% complete response rate, while mosunetuzumab produced a 73.5% response rate and 59.2% complete response rate.
For comparison, R-mini-CHOP, which uses reduced doses of chemotherapy drugs, is used for some older or frail patients. Chihara said toxicity remains a concern and about one in four patients may not complete six cycles. These figures and expert assessments were reported by MedPage Today; the source material does not establish that the newer regimens are superior in a head-to-head trial.
Treatment Choices Beyond Reduced Chemotherapy
The findings matter because DLBCL often affects older adults, some of whom have frailty or other health conditions that make standard-dose chemotherapy difficult. The average age at DLBCL onset is about 65, and a significant proportion of patients are 80 or older. Treatment decisions can depend on biological fitness as well as chronological age, according to Pallawi Torka, MD, of Memorial Sloan Kettering Cancer Center.
If further follow-up supports the early results, bispecific antibody regimens could offer some patients an active treatment option when full-dose chemotherapy is unsuitable. The results do not yet show that these treatments cure DLBCL or that they are appropriate for every older patient. Infections and treatment-related side effects remain important considerations, and the studies cited do not establish a single preferred regimen.
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How Older Patients Are Treated
For decades, R-CHOP—rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone—has been a standard treatment for fit older patients with newly diagnosed DLBCL. After results from the POLARIX trial, polatuzumab vedotin combined with rituximab and the CHOP drugs also became an established frontline standard for those patients.
For older people considered unfit or frail, clinicians may use R-mini-CHOP, which keeps the standard rituximab dose while reducing doses of the chemotherapy drugs. Chihara told MedPage Today that reduced chemotherapy can still be hard to tolerate and may produce a suboptimal response. Torka said that age assessments should also account for biological age and fitness, particularly for patients younger than 80, whose needs may vary.
“Age is just a number, the chronological age. The other thing that we have to be mindful of is the biological age.”
— Pallawi Torka, MD, Memorial Sloan Kettering Cancer Center
Durability and Infection Risks
The cited results are from phase II studies, and the source material does not provide head-to-head comparisons among the regimens. It also does not establish whether the reported responses will lead to durable remission or cure. Torka said updated follow-up for the glofitamab combination was expected, and that time would help distinguish remission from cure.
Bispecific antibodies can cause cytokine release syndrome, neurotoxicity and infections, Torka said. She highlighted viral and respiratory infections among concerns for older patients. The studies summarized here do not resolve how best to reduce those risks, or identify which patients are most likely to benefit from each approach.
Longer Follow-Up and Safer Use
Researchers will need to report longer-term outcomes to show whether responses persist and how survival compares with existing approaches. Updated data from the glofitamab combination study, including the two-year follow-up Torka anticipated, may add information about the durability of remission.
Further work also needs to clarify how clinicians can prevent or manage infections during treatment and how to select patients based on fitness, health conditions and treatment tolerance. Until more evidence is available, treatment choices remain a matter for patients and their oncology teams, weighing potential benefits against side effects and individual health needs.
Key Questions
What is DLBCL?
Diffuse large B-cell lymphoma is a type of lymphoma, a cancer that affects cells of the immune system. The source report describes it as a disease with an average onset age of about 65.
What did the bispecific antibody studies report?
Several phase II studies reported responses in older or unfit patients with newly diagnosed DLBCL. Results varied by regimen: for example, a glofitamab combination reported overall response rates of 90% to 96% across treatment cycles, while other studies reported complete response rates from 58% to 86%. These figures come from separate studies and should not be treated as direct comparisons.
Are bispecific antibodies proven to cure DLBCL in older patients?
No cure is established by the results described. The studies reported responses and, in some cases, one-year outcomes. Longer follow-up is needed to determine how durable the remissions are.
What risks did experts identify?
Potential side effects include cytokine release syndrome, neurotoxicity and infections, according to Torka. She highlighted viral and respiratory infections as an ongoing concern for older patients.
Source: rss
