Patients with large B-cell lymphoma who achieve a complete response to glofitamab are very likely to remain in remission 12 months after the end of treatment, according to Martin Hutchings, MD, PhD, of Rigshospitalet in Copenhagen, who reported these findings at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition.1
“Most patients who achieved a complete response at the end of treatment experienced durable responses in the absence of continued treatment.”— Martin Hutchings, MD, PhD
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“Most patients who achieved a complete response at the end of treatment experienced durable responses in the absence of continued treatment,” said Dr. Hutchings. He reported sustained remission for 37 (61%) of 61 patients in his study 12 months after they completed 12 cycles of glofitamab; another 17 patients were being followed but had not yet reached 12 months. And an estimated 79% of all responders had complete remissions lasting at least 2 years from the initial response, he said.
The study evaluated long-term outcomes in 291 patients with relapsed/refractory large B-cell lymphoma in the pivotal phase II trial as well as in phase I/II, which encompassed dose ranges from 0.005 mg to the recommended phase II dose of 30 mg. The analysis focused on the 61 patients in complete response at the end of treatment and the duration of responses after cessation of therapy.
About Glofitamab and the Study
Glofitamab is a CD20 x CD3 T-cell–engaging bispecific monoclonal antibody with a novel 2:1 (CD20:CD3) configuration that redirects T cells to eliminate normal and malignant B cells. It is an off-the-shelf treatment that is administered intravenously for a fixed duration of 12 cycles. In pivotal expansion cohorts of an ongoing phase I/II study, recently published in The New England Journal of Medicine,2 glofitamab induced frequent and durable complete responses (median not reached) in patients with relapsed/refractory large B-cell lymphoma.
At the ASH meeting, Dr. Hutchings presented data for the duration of complete remission from the end of treatment in patients enrolled in the dose-escalation and -expansion phases of this study. The 291 previously treated patients had diffuse large B-cell lymphoma not otherwise -specified, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma or transformed follicular lymphoma. They received 1,000 mg of obinutuzumab pretreatment (to mitigate cytokine-release syndrome) 7 days prior to the first dose of glofitamab, followed by glofitamab for up to 12 cycles (median = 8.3 months). Glofitamab was given at a fixed dose (0.6–25 mg) or with step-up dosing (target dose = 16 mg or 30 mg) every 3 weeks. Patients with disease progression after a prior response could be retreated.
Of the 291 enrolled patients, the objective response rate was 52.6%, with 35.4% achieving complete responses and 17.2%, partial responses. Median time to first complete response was 43 days, and there were 61 patients still in complete response at the end of treatment. Compared to patients without a complete response at the end of treatment, these patients were more likely to have received at least three prior lines of therapy and to have undergone a stem cell transplant, and they were less likely to have primary refractory disease, to be refractory to their last treatment, or to be refractory to prior chimeric antigen receptor (CAR) T-cell therapy.
Among patients with complete responses at the end of treatment, 61% remained in complete response at 12 months and 28% had not reached the 12 months of follow-up. After 12 months of follow-up, seven patients had discontinued study treatment: one due to progressive disease, two due to death from lymphoma, two due to receipt of an allogeneic transplant, one due to physician decision, and one lost to follow-up.
Two patients with progressive disease on the study have been retreated, and both have attained complete responses. These two patients reflect a larger group who anecdotally have also responded to retreatment, Dr. Hutchings noted.
From the time of the initial occurrence of a complete response until disease progression or death, the durability of responses was demonstrated. At a median follow-up of 18.1 months from the first complete response and a median of 11.5 months from the end of treatment, median duration of complete response was not reached, and 79.1% of patients had complete responses lasting 2 years or more. He added that among patients with extended follow-up, including quite a few treated at lower dose ranges, the remissions have persisted beyond the 12-month point.
“Off-treatment disease progression is uncommon in these heavily pretreated patients who are highly refractory and who are in complete response at the end of treatment,” he commented. “The estimated progression-free survival for patients with complete responses lasting at least 2 years is almost 80%.”
In the discussion period, Dr. Hutchings was asked whether he considers glofitamab to be a potentially curative therapy. He responded: “I think yes, but I do not actually know, because it’s clear we need longer follow-up. I do believe there is curative potential. My fellow investigators and I have shared many good stories of patients who have been followed for up to 3, and even 4, years in complete response after the end of treatment.”
DISCLOSURE: Dr. Hutchings reported financial relationships with AbbVie, Celgene, Genmab, Janssen, Roche, and Takeda.
1. Hutchings M, Carlo-Stella C, Morschhauser F, et al: Relapse is uncommon in patients with large B-cell lymphoma who are in complete remission at the end of fixed-course glofitamab treatment. 2022 ASH Annual Meeting and Exposition. Abstract 441. Presented December 11, 2022.
2. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al: Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 387:2220-2231, 2022.
Julio C. Chavez, MD, Associate Member in the Lymphoma Section of the Department of Malignant Hematology at Moffitt Cancer Center, Tampa, who co-moderated the session where the glofitamab study was presented, shared his thoughts with The ASCO Post.
“Glofitamab has great activity in high-risk...