Dr Vose on the Investigation of Epcoritamab in Relapsed/Refractory Follicular Lymphoma

Julie M. Vose, MD, MBA, division chief, Neumann M. and Mildred E. Harris Professor, physician, oncology and hematology, Division of Hematology and Oncology, University of Nebraska Medical Center; recipient, 2022 Giants of Cancer Care® award for lymphoma, discusses the investigation of epcoritamab-bysp (Epkinly) in patients with relapsed/refractory follicular lymphoma (FL) in the FL C1 OPT cohort of the phase 1/2 EPCORE NHL-1 trial (NCT03625037).

Notably, these data were presented at the 

 for the treatment of adult patients with relapsed/refractory FL who have received 2 or more lines of systemic therapy.

In presenting the rationale for the EPCORE study optimization cohort, Vose begins by saying that the goal of evaluating epcoritamab in this cohort was to mitigate cytokine release syndrome (CRS) and neurologic toxicity in patients with FL. Simple measures, such as administering dexamethasone before initial doses, outpatient hydration, and selectively withholding antihypertensives, resulted in significantly reduced CRS rates and eliminated grade 3 CRS incidents, with no observed neurologic toxicity compared with findings from prior studies, she shares. These adjustments were implemented to enhance patient safety and treatment tolerability, Vose notes.

The findings from the FL C1 OPT cohort showcased the safety profile of epcoritamab therapy with these new measures juxtaposed against findings from the overall EPCORE trial population without the optimization cohort, she continues. Notably, the rates of CRS were substantially lower in the FL C1 OPT cohort, and epcoritamab was associated with negligible neurotoxicity, in contrast to the safety findings in the overall EPCORE population, Vose reports. Furthermore, hospitalization when receiving the full dose of epcoritamab, which was previously mandatory, became optional in this updated cohort, facilitating outpatient treatment for many patients and underscoring the feasibility and benefits of the optimization strategies employed, she explains.

These safety enhancements mark significant progress in refining the treatment protocol for patients with FL within the EPCORE study, promising improved outcomes and treatment experiences, Vose concludes.

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Julie M. Vose, MD, MBA, discusses the investigation of epcoritamab in relapsed/refractory follicular lymphoma.

Dr Vose on Mitigating Epcoritamab-Associated CRS and Neurologic Toxicities in R/R DLBCL

Julie M. Vose, MD, MBA, division chief, Neumann M. and Mildred E. Harris Professor, physician, oncology and hematology, Division of Hematology and Oncology, University of Nebraska Medical Center, discusses the mitigation of treatment-related toxicities with epcoritamab-bysp (Epkinly) in an optimization cohort of adults with relapsed/refractory diffuse large B‑cell lymphoma (DLBCL) from the phase 1/2 EPCORE™ NHL-1 trial (NCT03625037).

the FDA granted accelerated approval to epcoritamab for pretreated patients with relapsed or refractory DLBCL

 not otherwise specified. The decision was supported by findings from the dose expansion portion of EPCORE NHL, in which single-agent subcutaneous epcoritamab produced deep, durable responses with a manageable safety profile in this patient population.

Notably, cytokine release syndrome (CRS) events in the dose expansion portion of the trial were primarily low grade, and subcutaneous administration, step-up dosing, and premedication with prednisolone, were used to mitigate events. To further investigate whether mitigation strategies can reduce toxicities and improve outcomes with epcoritamab monotherapy, researchers created an optimization cohort of patients previously treated with 2 or more lines of systemic therapy, Vose begins.

Patients received subcutaneous epcoritamab in 28-day cycles: weekly for cycles 1 to 3, every 2 weeks for cycles 4 to 9, and every 4 weeks thereafter or until progressive disease or unacceptable toxicity occurred. Two step-up doses preceded 48-mg full doses, Vose adds.

To address CRS, cycle 1 of the optimization cohort mandated 15 mg of dexamethasone as premedication on days 1, 8, 15, and 22, with prophylaxis on days 2 to 4, 9 to 11, 16 to 18, and 23 to 25,

 alongside diphenhydramine and acetaminophen on the same days. Hydration was strongly recommended, and antihypertensive medications were withheld for 24 hours before epcoritamab administration. Patients were advised to monitor their temperatures after the first 4 doses, with optional hospitalization and inpatient observation.

Julie M. Vose, MD, MBA, discusses the mitigation of toxicities with epcoritamab in an optimization cohort of patients with relapsed/refractory DLBCL. 

Julie M. Vose, MD, MBA, division chief, Neumann M. and Mildred E. Harris Professor, physician, oncology and hematology, Division of Hematology and Oncology, University of Nebraska Medical Center, discusses the investigation of tazemetostat (Tazverik) vs placebo when given in combination with lenalidomide (Revlimid) and rituximab (Rituxan) in patients with relapsed/refractory follicular lymphoma (FL) in the phase 3 SYMPHONY-1 study (NCT04224493).

The double-blind, randomized, active-controlled, 3-stage trial’s eligibility criteria encompass patients who have relapsed/refractory FL regardless of 

 mutation status, Vose begins. Importantly, the presence or absence of this mutation does not affect a patient's ability to participate in the study, she states. Instead, this genetic factor will be assessed at a later stage by the investigative team. Patients entering the trial are randomly assigned to receive rituximab plus lenalidomide with or without the addition of tazemetostat, Vose explains. In the other arm of the trial, patients receive a placebo, Vose says, adding that the randomized design of this trial ensures patients remain unaware of the specific treatment they are receiving.

One aim of this trial was to maximize the duration of response (DOR) for patients with relapsed/refractory FL who receive tazemetostat plus lenalidomide and rituximab compared with standard lenalidomide plus rituximab, she expands. A key motivating factor for enrolling patients in this trial is to improve response rates in this patient population, Vose says. When administered as a single agent, tazemetostat elicits a modest response rate. Therefore, continuous efforts are underway to enhance both the objective response rate (ORR) and the DOR with this agent in patients with relapsed/refractory FL, she emphasizes.

In the current single-agent trials investigating this agent, the ORRs and DORs are considered moderate, she notes. However, by combining tazemetostat with established standard therapies, investigators hope to achieve results that exceed those that each agent could achieve on its own, Vose continues. This approach is driven by the goal of providing more effective and durable treatment options for patients with relapsed/refractory FL, she concludes.

Julie M. Vose, MD, MBA, discusses the investigation of tazemetostat vs placebo when given in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma in the phase 3 SYMPHONY-1 study.


Dr Vose on the SYMPHONY-1 Trial in Relapsed/Refractory Follicular Lymphoma

Julie M. Vose, MD, MBA, Neumann M. and Mildred E. Harris Professor, chief, Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center, discusses the use of CAR T-cell therapy in non-Hodgkin lymphoma (NHL).

Currently, CAR T-cell therapies have FDA indications in relapsed/refractory diffuse large B-cell lymphoma (DLBCL), as well as mantle cell lymphoma (MCL). However, this treatment modality is being evaluated for use in several subtypes of NHL in ongoing clinical trials, Vose says. 

For example, trials are investigating CAR T-cell therapy in follicular lymphoma, chronic lymphocytic leukemia, and small lymphocytic lymphoma. Additionally, other products beyond those FDA approved are being tested in DLBCL and MCL, Vose concludes.

Julie M. Vose, MD, MBA, discusses the use of CAR T-cell therapy in non-Hodgkin lymphoma. 


Dr. Vose on the Use of CAR T-Cell Therapy in Non-Hodgkin Lymphoma 

Julie M. Vose, MD, MBA, Neumann M. and Mildred E. Harris Professor, chief, Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center, discusses the potential utility of CAR T-cell therapy across the non-Hodgkin lymphoma (NHL) paradigm.

CAR T-cell therapy is approved for use in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma; however, CAR T-cell therapies are limited to clinical trials in all other subtypes of NHL, says Vose. Although each trial has specific eligibility criteria, CAR T-cell therapy is typically being evaluated for use in the third- or fourth-line settings for patients who have progressed on chemoimmunotherapy or other targeted agents, Vose explains. As such, it is difficult to predict where these products will be integrated into the paradigms if they move forward in clinical development.

However, comparative trials are needed to determine whether CAR T-cell therapy is more efficacious and safer vs other standard options for patients with NHL, Vose explains. Additionally, it is likely that CAR T-cell therapy will be evaluated in earlier lines of treatment for certain patient populations, such as high-risk DLBCL. Finally, long-term data from ongoing clinical trials are needed to determine whether the response associated with CAR T-cell therapy is durable and whether toxicity issues resolve in the long term, Vose concludes.

Julie M. Vose, MD, MBA, discusses the potential utility of CAR T-cell therapy across the non-Hodgkin lymphoma paradigm.  



Dr. Vose on the Potential Utility of CAR T-Cell Therapy Across Non-Hodgkin Lymphoma 

Julie M. Vose, MD, MBA, Neumann M. and Mildred E. Harris Professor, chief, Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center, discusses future research efforts with CAR T-cell therapy in lymphoma.

Ongoing clinical trials are evaluating CAR T-cell therapies, as well as other types of treatment, for patients with lymphoma, Vose says. Moreover, some studies are investigating different designs of CAR T-cell therapies, utilizing CAR T-cell therapy in various subtypes of lymphoma, and potentially incorporating the cellular therapy into earlier lines of treatment, Vose says.These efforts may yield opportunities to decrease CAR T-cell therapy­–related toxicities for patients, Vose explains.

Additionally, research efforts are evaluating whether combination regimens with CAR T-cell therapies and other agents, such as BTK inhibitors, are feasible for patients with lymphoma, Vose says. It may also be possible to utilize pre- and post-CAR T-cell therapy radiation to try to enhance efficacy, Vose continues. Additionally, evaluating different types of monoclonalantibodies, bispecific antibodies, or other new agents alone or in combination with CAR T-cell therapy could lend future treatment options for patients, Vose concludes.

Julie M. Vose, MD, MBA, discusses future research efforts with CAR T-cell therapy in lymphoma.

 Dr. Vose on Future Research Efforts With CAR T-Cell Therapy in Lymphoma

Julia M. Vose, MD, professor and chief in the Division of Oncology/Hematology at University of Nebraska Medical Center, discusses the rationale for the phase I/II trial of acalabrutinib (Calquence) plus pembrolizumab (Keytruda) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

As single agents, both acalabrutinib and pembrolizumab have shown activity in other types of lymphoma and their toxicities do not overlap. This makes them the combination of choice for patients with relapsed/refractory DLBCL, Vose explains.

She says that despite the low complete response rate and short duration of response seen overall in the study, several patients showed meaningful activity (>24 months) and the combination was well tolerated. This is rationale to explore the combination further.

15th International Conference on Malignant Lymphoma

Julia M. Vose, MD, professor and chief in the Division of Oncology/Hematology at University of Nebraska Medical Center discusses the rationale for the phase I/II trial of acalabrutinib (Calquence) plus pembrolizumab (Keytruda) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Dr. Vose on Acalabrutinib/Pembrolizumab Combo in DLBCL

Julie M. Vose, MD, MBA, professor, internal medicine, chief, Division of Oncology & Hematology, University of Nebraska Medical Center, discusses the importance of genomic analysis in patients with non-Hodgkin lymphoma (NHL).

Many patients with NHL can be cured, says Vose, but for those with more aggressive disease, or with genetic drivers, more work needs to be done to individualize treatment. Looking at the specific genetic makeup of a patient and targeting those abnormal pathways is the first step, according to Vose. Although, there are some challenges, as there are often multiple pathways to target, and cells can get around these pathways. Vose says that combinations may be a way to address that escape mechanism.

Vose says that genomic analysis needs to be done in every patient with NHL in order to understand their disease and treat them properly. This is particularly true for high-risk patients who usually have less options. Fluorescence in-situ hybridization, and analysis for BCL2, BCL3, and MYC should be done in every patient with diffuse large B-cell lymphoma to increase their chances at a good outcome, or for referral to a clinical trial.

Julie M. Vose, MD, MBA, professor, internal medicine, chief, Division of Oncology & Hematology, University of Nebraska Medical Center, discusses the importance of genomic analysis in patients with non-Hodgkin lymphoma.
 

Julie M. Vose, MD

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