Managing Adverse Event Profiles for Three Bispecific Antibodies Approved for Lymphoma

Three bispecific antibodies were FDA approved as monotherapies to treat lymphoma in 2022 and 2023, explained Aseala Abousaud, PharmD, BCOP, oncology clinical pharmacy specialist, lymphoma, Emory Winship Cancer Institute, during a presentation at the Hematology/Oncology Pharmacy Association (HOPA) Annual Conference 2024 in Tampa, Florida. Those therapies include mosunetuzumab-axgb (Lunsumio; Genentech) to treat relapsed or refractory (R/R) follicular lymphoma (FL), epcoritamab-bysp (Epkinly; Genmab and AbbVie) to treat R/R diffuse large B-cell lymphoma (DLBCL), and glofitamab-gxbm (Columvi; Genentech) to treat R/R DLBCL or large B-cell lymphoma (LBCL).

Currently, all 3 bispecifics are approved for treatment after 2 or more lines of systemic therapy, according to Abousaud. However, there are numerous clinical trials underway assessing these therapies for other indications, including using them earlier on in treatment.

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“I do not think these drugs are going to stay in the third-line setting as monotherapy; I foresee them coming to frontline therapy,” Abousaud said during the HOPA session. “Of course, pharmacists play a valuable role in education, monitoring, and managing adverse event [AE] profile [for these therapies].”

During treatment, cytokine release syndrome (CRS) is the most serious AE pharmacists should be monitoring for, according to Abousaud. In the GO29781 trial (NCT02500407) evaluating mosunetuzumab-axgb, investigators found that grade 1/2 CRS occurred at a rate of 42% (n=38), and grade 3/4 occurred at 2% (n=2). Further, the median time to CRS was 27 hours. Additionally, immune effector cell-associated neurotoxicity syndrome (ICANS) occurred as well, with patients experiencing confusional state (3%), disturbance in attention (1%), and cognitive disorder (1%).

Abousaud explained further that mosunetuzumab-axgb is administered on a 21 day cycle and given intravenous (IV). The first cycle of therapy is a step-up dose to help prevent CRS.

“On day one, they get 1 milligram IV over 4 hours. They come back the next week on day 8, where they get 2 milligrams IV over 4 hours,” Abousaud said during the session. “Then on day 15, they get their first loading dose of 60 milligrams over 4 hours. That following week starts cycle 2 day 1, where they get another loading dose of 60 milligrams. This time, if they didn't have any CRS within the first cycle, you can decrease that infusion time to 2 hours, and from there, it's a every 21-day cycle using a maintenance dose of 30 milligrams IV over 2 hours.”

If patients have a complete response, then they go onto observation, explained Abousaud. If they have a partial response or stable disease, then patients can continue up to 17 cycles, but this is a fixed duration regimen.

In the EPCORE NHL-1 trial, epcoritamab-bysp was evaluated in a population with R/R DLBCL, including among patients with DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after 2 or more lines of systemic therapy. In this trial, CRS grade 1/2 occurred at a rate of 47% (n=74), and grade 3/4 occurred at 2.5% (n=4). Any grade ICANS occurred at a rate of 6.6% (n=10).

Epcoritamab-bysp is given an a 28-day cycle with subcutaneous injection, and it also has a step-up dose to help prevent CRS in patients with DLBCL, explained Abousaud. Patients start off with 0.16 milligrams, and then come back the following week to get 0.8 milligrams. Specifically, day 15 is when patients get their full dose, and at this dose, median time to CRS was 20.6 hours.

“There is a recommendation in the package insert that patients should be hospitalized for 24 hours after administration of this dose,” Abousaud said during the session. “On day 22, they get that last full dose for cycle 1, and then they'll continue weekly for cycles 2 through 3, every other week for cycles 4 through 9, and then monthly for cycles 10 plus—this is indefinite treatment, so they do continue as long as they're not progressing or have any symptoms.”

Glofitamab-gxbm was studied in the NP30179 (NCT03075696) trial, with 80% of the patients included having R/R DLBCL, not otherwise specified, and 20% with LBCL arising from FL. Patients included in the trial received at least 2 prior lines of systemic therapy, with patients excluded if they have active or previous central nervous system lymphoma or disease. CRS grade 1/2 occurred in 60% (n=93) of patients, and grade 3/4 occurred in 4% (n=4). Any grade ICANS occurred at a rate of 9% (n=12).

Glofitamab-gxbm is given on a 21-day cycle IV, Abousaud explained. Also, patients should be given obinutuzumab (Gazyva; Genentech) on day 1 to prevent CRS, so it is a part of the regimen with glofitamab-gxbm, according to Abousaud.

“[Obinutuzumab] helps to deplete the B cells before you start to give glofitamab-gxbm. It also has a similar epitope or the same epitope as glofitamab-gxbm, so it does help to compete for that spot. So, as you're increasing the dose, you're helping to diminish the chances of [CRS],” Abousaud said.

Day 8 is the first dose of glofitamab-gxbm, at which time patients should be given a step-up dose of 2.5 milligrams IV over 4 hours. The package insert does recommend that patients should be hospitalized during and after administration for 24 hours, according to Abousaud. On day 15, patients get 10 milligrams IV over 4 hours.

“The recommendation on the package insert is if they do get any grade CRS with that first dose on day 8, that they get hospitalized for day 15 as well,” Abousaud said during the session. “On cycle 2 the following week, they start cycle 2 day 1, [which is] when they get their first full dose of 30 milligrams over 4 hours.”

Abousaud explained further that once patients get to cycle 3 plus, they can continue on 30 milligrams. However, at this point, the duration can change to a 2-hour infusion if the patient tolerated the therapy in the first couple of cycles.

According to Abousaud, the potential for these bispecific antibodies to transform the treatment landscape for several indications is significant.

“The future is bright in lymphoma,” Abousaud said during the session. “These [bispecifics are] being studied in mantle cell lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma [as well]. So, these bispecifics are coming, just prepare yourself [because] I know you can treat these patients in the outpatient setting and feel safe about it.”

REFERENCE

Abousaud A. Bispecifics in Lymphoma. Presented at: Hematology/Oncology Pharmacy Association Annual Conference 2024; Tampa, Florida; April 3-6, 2024.