Bispecific antibody, still with toxicity though, although pts had pretreatment with obinutumzumab to mitigate CRS. Response rate 35% in pts who received CAR-T therapy.
The prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is poor. Glofitamab is a bispecific antibody that recruits T cells to tumor cells.
In the phase 2 part of a phase 1–2 study, we enrolled patients with relapsed or refractory DLBCL who had received at least two lines of therapy previously. Patients received pretreatment with obinutuzumab to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy (12 cycles total). The primary end point was complete response according to assessment by an independent review committee. Key secondary end points included duration of response, survival, and safety.
Of the 155 patients who were enrolled, 154 received at least one dose of any study treatment (obinutuzumab or glofitamab). At a median follow-up of 12.6 months, 39% (95% confidence interval [CI], 32 to 48) of the patients had a complete response according to independent review. Results were consistent among the 52 patients who had previously received chimeric antigen receptor T-cell therapy (35% of whom had a complete response). The median time to a complete response was 42 days (95% CI, 42 to 44). The majority (78%) of complete responses were ongoing at 12 months. The 12-month progression-free survival was 37% (95% CI, 28 to 46). Discontinuation of glofitamab due to adverse events occurred in 9% of the patients. The most common adverse event was cytokine release syndrome (in 63% of the patients). Adverse events of grade 3 or higher occurred in 62% of the patients, with grade 3 or higher cytokine release syndrome in 4% and grade 3 or higher neurologic events in 3%.
Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4. (Funded by F. Hoffmann–La Roche; ClinicalTrials.gov number, NCT03075696. opens in new tab.)
This combination had impressive results but led to a high rate of ventricular arrythmias (9%), hence the combination is not recommended. Another study with the combination and rituximab was also suspended, the etiology of the higher rate of Vent arrhythmias is not known. This combination in another lymphoid malignancies did not lead to that rate of toxicity.
Final results from the ASPEN study confirm the strong long-term superiority of zanubrutinib over ibrutinib in symptomatic WM. While overall survival (OS) and progression-free survival (PFS) end-points are still to be reached, demonstrating the good prognosis of this disease, toxicities and response rates are much better with zanubrutinib. This is a cat-1 indication oof NCCN and a compelling option for use in this population.
Speaking of tafatistamab, it seems it is fairly tolerable in first line with almost 75% CR added to RCHOP, adding lenolidomie 86% CR, but this is a phase 1b. Awaiting phase 3 data, we may have another first line option or may the first line option.
There are too many options for DLBCL now with monoclonal antibodies, bispecific and CAR-T therapy, but in frail patients, this might be an option. Tafatistamab with lenalidomide had higher ORR (55vs 50) and CR( 37 vs 27%) but this is comparing different trials, and this trial had mostly elderly pts, I do feel tafatistamab is fairly well tolerated though. But when in doubt this seems to be a fair option.
CAR-T for second line is better than standard of care, the question is: how about compared to BITE therapy? Future is exciting for those patients.
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