Randy Dotinga

December 07, 2024

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SAN DIEGO — Compared with clinical trials, a real-world retrospective analysis has linked the bispecific antibodies epcoritamab (Epkinly) and glofitamab (Columvi) to somewhat poorer outcomes in relapsed or refractory large B-cell lymphoma (LBCL).

In a presentation here at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0 – 3.9) and median overall survival was 7.2 months (95% CI, 6.1 – not reached). 

It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”

He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizeable fraction will respond, and some will maintain remissions.'”

According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T-cell engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”

The US Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023. 

“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”

The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n=139; glofitamab, n=70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).

“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.

In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%). 

The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients,” he added. 

Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.

“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”

In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”

Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”

In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” he said, because they offer insight into how the drugs work. 

“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, ” he said. “These are learnings that often come after approval.” 

He added that it’s clear that “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”

Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.” 

Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”

There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol Myers Squibb, Regeneron, and ADC Therapeutics. 

Randy Dotinga is an independent writer and board member of the Association of Health Care Journalists. 

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