The Future of Bispecific Antibodies in Aggressive B-Cell Lymphomas

In a presentation at the Society of Hematologic Oncology (SOHO) 2024 Annual Meeting, held in Houston, Texas, Krish Patel, MD, director of the lymphoma program and hematologic malignancies and cellular therapy at Swedish Cancer Institute, discussed the use of bispecific antibodies (bsAbs) in aggressive B-cell lymphoma and what the future holds for these agents. Specifically, Patel emphasized the potential use of bsAbs as monotherapies.

Patel began the session by listing 2 bsABs—epcoritamab (Epkinly; AbbVie), which is administered subcutaneously in a treatment to progression model, and glofitamab (Columvi; Genentech), which is given in a fixed duration up to 12 cycles—and their use in relapsed or refractory large B-cell lymphoma (LBCL). Both bsAbs have been available for commercial use in the US for about a year and a half, primarily in the third line setting for LBCL. Patel acknowledged that although there aren’t direct comparisons between the 2 therapies, in terms of efficacy, they are quite comparable.

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The median progression-free survival (PFS) is shorter for both drugs (epcoritamab: 4.4 months and 6-month PFS: 44% [95% CI 36-52]; glofitamab: 4.9 months, 12-month PFS: 37% [95% CI 28-46]), but looking at landmark analyses, patients achieve deep responses and complete responses (CR) early on and tend to have durable responses. Patel said about two-thirds of patients achieving a CR during cycle 3 and continuing to maintain responses after 2 or more years. Additionally, in the EPCORE NHL-1 (NCT03625037) and NP30179 DLBCL (NCT03075696) trials, approximately 60% to 70% of patients who received epcoritamab and glofitamab, respectively, received the bsAbs in the fourth line setting with about one-third of patients receiving prior chimeric antigen receptor (CAR) T-cell therapy. The CR rate for both agents was considered consistent and comparable in those who did not see efficacy with CAR T compared with CAR T-naïve patients.

Further, Patel noted that although CAR T-cell therapies were initially approved in the third line setting for relapsed or refractory diffuse LBCL (DLBCL), the “dropout” rate—or area in which CAR T is unable to be delivered—is considerably high, even in pivotal clinical trials. In the DLBCL setting, approximately 15% of patients in clinical trials do not receive autologous CAR T therapies, with death occurring in 3% to 4% of patients; however, Patel emphasized that this proportion may be worse in real-world data because databases typically only include infused patients.

“I would say that at least in my own practice, [the third line setting] is largely where I think about [bsAbs], and I think this is common for others as well. [Epcoritamab and glofitamab] probably have the best data for post-CAR T outcomes in the third line setting. I still think clinical trials are very important for patients that are failed by CAR T-cell therapy, but for those that don't have access to trials, are not eligible, or, ultimately, really just need to be able to receive care somewhere closer to home, bsAbs may present a good option for those patients,” emphasized Patel. “And then [in] a lot of places, there is no market access for CAR T, so I would say—at least at this moment in time—this seems to be where we are most likely to be using [CD20 × CD3] bsAbs.”

Based on the ZUMA7 (NCT03391466), TRANSFORM (NCT03575351), and PILOT (NCT03483103) studies, Patel said that CAR T may be suitable as a treatment option for patients with DLBCL in the second line setting; however, other options for those who are transplant ineligible should be available. The STARGLO trial (NCT04408638) showed that in patients who were ineligible for transplant glofitamab, when in combination with gemcitabine and oxaliplatin, presented a 24-month OS of approximately 52.8% compared with those who received rituximab (Rituxan; Biogen, Genentech) with gemcitabine and oxaliplatin (33.5%). Additionally, PFS for the glofitamab regimen was also superior (51.7%) compared with the rituximab regimen at 12 months (25.2%).

“In the near future…[maybe] we will be using bsAbs in the second line setting perhaps for those transplant ineligible patients. Again, while CAR T-cell may be an option [it] may not be feasible. Or again, those patients where, [for example,] disease kinetics and biology would suggest otherwise,” said Patel. “This is also a regimen we can use post-CAR T and while there weren't a large number of post-CAR T patients here, we certainly already have experience using bsAbs, and so, the combination of chemoimmunotherapy might be beneficial for these patients as well. Although, I would say we have cautious on things like infection risk and cytopenias.”

Patel concluded the session by emphasizing the use of bsAbs in the third line setting, noting that he prefers to use them over other treatments in patients who either had second line CAR T failure or when CAR T is non-feasible. Additionally, he discusses that earlier phase trials exploring glofitamab and epcoritamab with a modified version of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (pola-R-CHP) show promise; however, phase 3 trial results are needed to confirm these findings.

“We don't yet have an approval [for bsAbs] in the second line, but we anticipate this may come and perhaps this is another area where we'll see increasing use of bsAbs in those patients who are transplant ineligible or potentially not able to receive CAR T-cell therapy as a second line therapy,” said Patel. “And in the frontline setting—as we've reminded many times before—we really need to do the trials that are going to improve the benefit, but these are already undergoing and accruing rapidly, and so, hopefully we'll have some answers there soon.”

REFERENCE

Patel, K. Session X—Aggressive B-Cell Lymphoma: Bispecific Antibodies in Aggressive B-Cell Lymphoma—Where Do They Fit In? Society of Hematologic Oncology Annual Meeting; Houston, Texas. September 4, to September 7, 2024.