Selecting Bispecific Antibody Therapies in RR DLBCL
Listen on your favorite podcast platform:
Key Points
-
The primary therapies for relapsed or refractory (RR) diffuse large B-cell lymphoma (DLBCL) are bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) therapies.
-
Minimal residual disease (MRD) may play a role in guiding treatment discontinuation, but more data are needed.
-
Immunoglobulin G (IgG) levels should be monitored and supported if necessary, especially in RR DLBCL.
On the Oncology Brothers podcast, Rahul Gosain, MD, MBA, and Rohit Gosain, MD, were joined by Carla Casulo, MD, of Wilmot Cancer Institute, and Tara Graff, DO, MS, of Mission Cancer + Blood. As part of the new “Challenging Cases” series, the doctors discussed 3 cases of RR DLBCL, with a focus on bispecific antibody therapies.
Although bispecifics are being evaluated in the frontline setting, they are currently approved only in RR DLBCL. Dr. Rahul Gosain emphasized that community oncologists should partner with tertiary care centers when patients relapse or become refractory.
Epcoritamab Versus Glofitamab in Diffuse Large B-Cell Lymphoma
The first case described a 73-year-old man with stage 4, non-germinal center B-cell (GCB), international prognostic index (IPI) 4 DLBCL. The patient had received Pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) and achieved a partial response.
After progression, the patient received R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) but became refractory. When considering further treatments, the patient had declined to receive CAR-T therapy.
Dr. Casulo said this case represents a complex but relatively common population. CAR-T therapy may be one of the most effective options available, she said, so she might further investigate whether it could be considered.
If CAR-T therapy is not viable, the primary bispecific antibody therapies would be epcoritamab and glofitamab. Epcoritamab is given subcutaneously and continued indefinitely, whereas glofitamab is given intravenously for a limited duration. Dr. Casulo added that epcoritamab requires greater use of steroids, which can affect quality of life.
The doctors agreed that, regardless of selected bispecific therapy, education for patients and community partners is necessary for managing potential adverse effects.
Roles of Minimal Residual Disease and Intravenous Immunoglobulin in DLBCL Treatment
Next, the doctors discussed the case of a 69-year-old woman with stage 3, non-GCB, IPI 3 DLBCL. The patient previously received R-CHOP and axicabtagene ciloleucel (axi-cel). After becoming refractory to axi-cel, the patient started epcoritamab, achieving a complete response (CR) at 4 months but requesting less infusion time.
Dr. Rohit Gosain asked if stopping epcoritamab could be considered based on MRD assessments. Dr. Graff said that MRD-guided treatment alterations are an ongoing topic of research and could play a role in selecting patients for individualized approaches like time-limited epcoritamab or indefinite glofitamab; however, more data are needed.
For this particular case, Dr. Graff pointed out that a patient who has received anti-CD20 therapy, CAR-T therapy, and a bispecific likely has B- and T-cell exhaustion, and MRD might be more relevant when considering treatment discontinuation to preserve cell function.
Dr. Rohit Gosain also posed the question of intravenous immunoglobulin (IVIG) and its role in RR DLBCL to prevent hypogammaglobulinemia. Dr. Graff said IVIG may be underused and emphasized monitoring IgG levels, especially in patients with relapsed or refractory disease. In her practice, she manages hypogammaglobulinemia with IVIG infusions every 3 months, potentially shortening to every 8 weeks, depending on the patient.
Treating a Patient With Travel Restrictions
The last case the doctors discussed was of an 82-year-old man with stage 3, non-GCB, IPI 4 DLBCL. The patient, who also had mild renal disease and diabetes, lived in a rural area and was restricted in travel. The patient previously received R-CHOP followed by Pola-BR (polatuzumab vedotin, bendamustine, and rituximab).
For this case, the doctors compared loncastuximab tesirine with tafasitamab and lenalidomide. Dr. Casulo said that, although these agents haven’t been compared head-to-head, they generally have similar rates of overall response and CR.
Tafasitamab and lenalidomide may be logistically challenging because of the number of infusions, Dr. Casulo said, so she would probably select loncastuximab for this patient. She highlighted pleural effusion, pericardial effusion, and peripheral edema as the primary adverse effects to monitor for, adding that photosensitivity may also be more of an issue in certain regions.
“I think the take-home here is that the treatment landscape has changed significantly,” Dr. Graff said. “It’s an awesome time for patients, with so many options, but it’s also a difficult time for clinicians.” She encouraged every oncologist, community or otherwise, to reach out to colleagues when deciding on treatment options or sequencing for individual patients.