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In a conversation with CancerNetwork®, Viviana Cortiana, fourth-year medical student in the Department of Medical and Surgical Sciences at the University of Bologna, and Yan Leyfman, MD, a resident physician from the Icahn School of Medicine of the Mount Sinai Health System, discussed their publication in the 

 titled “Expanding Horizons in T-cell Lymphoma Therapy: A Focus on Personalized Treatment Strategies.” Throughout the discussion, the authors spoke about the current lymphoma landscape, chimeric antigen receptor (CAR) T-cell therapy, and the evolving understanding of the tumor microenvironment.

Specifically, Cortiana covered a shift from histology-based classification to molecular tumor type classification using next-generation sequencing as well as a growing interest in biomarker-driven therapies. Regarding the limited efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in T-cell lymphoma, she listed potential advances in combination therapies for angioimmunoblastic T-cell lymphoma, which include combining PI3K and HDAC inhibition as well as CD30- and TRBC1-targeting CAR T-cell therapies.

Furthermore, Leyfman discussed strategies that “reprogram” the microenvironment to address malignant T cells, particularly through epigenetic and adoptive cell therapies. Leyfman concluded by discussing future implications for T-cell lymphoma treatment, emphasizing an emergence of precision medicines and armored CAR engineering strategies.

 outlined the available treatment options for peripheral T-cell lymphoma (PTCL), which include targeted therapies through EZH2 inhibition, chemotherapy with CHOP, CAR T-cell therapies, and allogeneic stem cell transplantation. Additionally, they highlighted encouraging results from clinical trials evaluating epigenetic-targeted therapies through the identification of molecular aberrations, which can help tailor treatments to individual patients.

Furthermore, the article explored limitations of chemotherapy as well as autologous stem cell transplantation (ASCT), which may not be feasible for older patients or those with comorbidities. Authors suggested that targeted therapies may enhance tumor specificity while reducing systemic toxicity. Given the risks associated with ASCT, they emphasized a focus on the incorporation of optimized treatment strategies, such as novel pharmaceuticals and combination therapies, into clinical practice for patients with PTCL.

Advances in next-generation sequencing and gene expression are reshaping T-cell lymphoma classification and the use of targeted therapies.

Highlighting Advancements in Personalized T-Cell Lymphoma Treatment

Following the 2024 Marginal Zone Lymphoma (MZL) Workshop, CancerNetwork® spoke with multiple attending clinicians about insights they shared regarding the disease state, covering the significance of the workshop and its contribution to advancing research in areas such as prognostic factors and managing adverse events (AEs) related to the disease.

Thomas Habermann, MD, professor of Medicine at the Mayo Clinic in Rochester, Minnesota, member of the Lymphoma Research Foundation’s Scientific Advisory Board, and MZL Workshop co-chair, spoke about the significance of the MZL Workshop. He highlighted the complexity of these types of diseases, which he believed warranted the establishment of the group.

According to Habermann, MZL is a “heterogenous group of disorders” that most contemporaries in the field “don’t quite appreciate.”

Next, Julie M. Vose, MD, MBA, George and Peggy Payne chair in oncology and chief of Hematology and Oncology at the University of Nebraska Medical Center, and co-editor-in-chief of 

®, spoke about how the MZL Workshop contributes to advancing research and improving outcomes for patients with MZL. She emphasized a need to be more inclusive when enrolling patients with MZL in clinical trials.

Then, James R. Cerhan, MD, PhD, professor of Epidemiology at the Mayo Clinic College of Medicine and Science, and Ralph S. and Beverly Caulkins Professor of Cancer Research, spoke about addressing research questions in MZL epidemiology to further disease understanding. He emphasized a need to further study newly identified risk factors of the disease, as well as identifying new treatment targets for patients with MZL.

Additionally, Alexandar Tzankov, MD, surgical pathologist and head of the Department of Histopathology and Autopsy at the Institute of Medical Genetics and Pathology at University Hospital Basel, and chair for the European Bone Marrow Working Group, discussed how prognostic factors for MZL may influence treatment. He described how the limited number of studies done with relatively small subsets of patients makes prognoses challenging, as prognostic factors have not been sufficiently explored.

Finally, Andrew D. Zelenetz, MD, PhD, medical director of Quality Informatics at Memorial Sloan Kettering Cancer Center, outlined challenges related to AE management of treatments for MZL. He emphasized that safety management practices for MZL are comparable with other B-cell lymphomas, suggesting that use of bridging therapy for CAR T cells and step-up dosing for bispecific antibodies may help with mitigating AEs.

Clinicians outline the significance of the MZL Workshop, where a gathering of international experts in the field discussed updates in the disease state.

Highlighting Insights From the Marginal Zone Lymphoma Workshop

 spoke with Andrew M. Evens, DO, MBA, MSc, about developments in the treatment landscape for adolescents and young adults (AYA) with lymphoma. He highlighted collaboration between adult and pediatric oncologists that may better standardize treatment for this population.

Evens is the deputy director for clinical services at the Rutgers Cancer Institute and system director of medical oncology and oncology lead at RWJBarnabas Health Medical Group.

Of note, Evens discussed an effort to “harmonize” efforts between adult and pediatric oncologists in treating AYA patients who may receive different treatment regimens, despite being similar in age. Furthermore, he highlighted 2 prominent trials that illustrated collaborative efforts from both adult and pediatric oncologists: the phase 3 SWOG S1826 trial (NCT03907488) and the phase 3 AHOD2131 trial (NCT05675410).

Regarding the SWOG trial, Evens highlighted the greater efficacy and tolerability of nivolumab (Opdivo) with doxorubicin hydrochloride (Adriamycin), vinblastine sulfate, and dacarbazine (AVD) vs the standard of care brentuximab vedotin (Adcetris) plus AVD.

“You could say it was, generally speaking, a double winner. [The nivolumab combination] was more effective at 2 years; the progression-free survival [PFS] was greater than 90%, [which was] a remarkable output. When I say a double winner, it was also largely better tolerated. There was less neuropathy, [fewer] infections, and less sepsis [vs brentuximab vedotin plus AVD]. Surprisingly, to a certain extent, [there were] not many immune-related adverse events outside of thyroid [events],” Evens said.

Furthermore, Evens discussed how collaboration between adult and pediatric oncology has impacted developments in the AYA lymphoma sphere. He placed a particular emphasis on the efforts of the Lymphoma Research Foundation, which convened multiple AYA lymphoma symposiums and established an AYA consortium. He then outlined unmet needs for this patient population, which included mitigating late toxicities following treatment and addressing inconsistencies in guidelines for lymphoma treatment in the AYA group.

Evens then discussed mitigating disparities and addressing barriers to care, underscoring a need to navigate the complexities of treatment for a patient population with a myriad of stressors. He concluded by highlighting resources available to AYA lymphoma groups, which include educational, medical, and psychosocial resources to best educate patients and express to them that they are not alone.

“At the end of the day, be an advocate. Be an advocate for yourself. Be an advocate for others and know that there are [many] resources and people out there to help. We want to make sure nobody has to go through this alone, and that they have the medical and other psychosocial resources available to them,” Evens concluded.

Herrera AF, LeBlanc M, Castellino SM, et al. Nivolumab+AVD in advanced-stage classic Hodgkin’s lymphoma. 

 2024;391(15):1379-1389. doi:10.1056/NEJMoa2405888

Henderson TO, Hu B, Keller F, et al. AHOD2131: A randomized phase 3 response-adapted trial comparing standard therapy with immuno-oncology therapy for children and adults with newly diagnosed stage I and II classic Hodgkin lymphoma. 

. 2023;142(suppl 1):3084. doi:10.1182/blood-2023-189652

Contemporary Concepts in Hematologic Oncology

A leader from the adolescent and young adult lymphoma space discusses how collaboration between adult and pediatric oncologists has transformed the field.

Collaboration Fosters Treatment Advancements for Young Lymphoma Populations

 spoke with Julie M. Vose, MD, MBA, and Avyakta Kallam, MD, about the evolution of their careers in the hematology-oncology space, including some of the critical advances and challenges associated with their work in the lymphoma field.

Vose is division chief, Neumann M. and Mildred E. Harris Professor at the University of Nebraska Medical Center, and co-editor-in-chief of 

. Kallam is an assistant professor in the Division of Lymphoma and Department of Hematology & Hematopoietic Cell Transplantation from City of Hope in Duarte, California.

Vose and Kallam discussed how they first developed a passion for researching lymphoma, which led them to become involved in various breakthroughs related to the use of treatment strategies such as autologous stem cell transplantation, bispecific antibodies, and CAR T-cell therapy. The conversation highlighted how this evolution of therapy options has helped improve patient outcomes while reducing hospitalization periods and minimizing toxicity.

The discussion also extended to the topic of overcoming various physical and social barriers while trying to advance in the lymphoma field. For example, Kallam described her experience with moving to the United States from India to complete her medical training, which involved adapting to a new culture and a new style of approaching treatment.

In the early stages of Vose’s career, there were far fewer women involved in oncology and medicine in general, contributing to the challenge of needing to work extremely hard to prove that she was equal to her male colleagues. Vose noted in the early days, she was considered a rarity in the field as one of very few women.

Vose and Kallam also brought up how their mentors have given them key pieces of advice from mentors that have stuck with them throughout their careers. They, in turn, offered wisdom to any woman looking to advance in the hematology-oncology space.

“The biggest piece of advice [I received] is to see the patient as a person—not just as a patient—to be able to get to know them and their families understand some of their struggles so that you can relate to them as a person,” Vose said.

The conversation also focused on the challenge of achieving work/life balance while making advances in the lymphoma space. Dedicating time to hobbies and finding support from friends and family members emerged as potential strategies for balancing professional responsibilities with one’s personal life.

“Life is too unpredictable to not do things that you enjoy doing,” Kallam said, recounting a bit of advice she had received from one of her mentors. “What we’re doing is important; we are impacting lives. We’re doing a lot of research, but at the same time, keep in mind to have fun along the way.”

Lymphoma Specialists on Instilling Confidence Throughout Their Careers

Leaders from the lymphoma space highlight the importance of mentorship in establishing their careers and impart advice to women looking to advance theirs.  

Overcoming Physical and Social Barriers in the Lymphoma Field

Tycel Phillips, MD, spoke with CancerNetwork

FDA’s accelerated approval of epcoritamab-bysp

(Epkinly) for patients with relapsed/refractory follicular lymphoma to discuss how this agent may impact the treatment paradigm.

Phillips, an associate professor in the Division of Lymphoma and Department of Hematology & Hematopoietic Stem Cell Transplantation at City of Hope in Duarte, California, reviewed data from the 

phase 1/2 EPCORE NHL-1 trial (NCT03625037)

 which ultimately supported the approval of epcoritamab in the aforementioned population. Topline results reported at the time of the agent’s approval showed an overall response rate (ORR) of 82% (95% CI, 74.1%-88.2%), with 60% of patients experiencing a complete response. Additionally, the median duration of response was not reached (NR; 95% CI, 13.7-NR).

Beyond the supporting data, Phillips highlighted how this approval may increase availability of treatment options for patients with follicular lymphoma, especially those who lack access to alternative therapies. He stated that readily available off-the-shelf bispecific antibodies like epcoritamab may bridge the gap for patients who are unable to access CAR T-cell therapies or travel to a major academic center for treatment.

Phillips also detailed strategies for mitigating some of the common toxicities that may occur following treatment with epcoritamab, which include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Although Phillips said that epcoritamab is usable in the third-line setting, he noted that bispecific antibodies like it “have a lot of potential for upward mobility,” as he anticipates further assessment of these treatments in the first or second line.

“As community oncologists get more and more comfortable with these drugs and have the structure to set up to safely administer [them] for the first month when most of the complications happen, more and more patients will be able to be treated, which will be a great benefit based on what we’ve seen in early response rates for these drugs,” Phillips said regarding the utility of bispecific antibodies like epcoritamab. “There’ll be a big benefit for the patient population in the long term as more community settings implement these drugs into their clinical practice.”

FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. News release. FDA. June 26, 2024. Accessed June 26, 2024. https://tinyurl.com/26s9myey

Bispecific antibodies including epcoritamab have “a lot of potential for upward mobility” in lymphoma, according to Tycel Phillips, MD.

Epcoritamab Approval Expands Bispecific Use in Follicular Lymphoma 

Although strides have been made with Bruton tyrosine kinase (BTK) inhibitors and CAR-T cell therapy, relapse and resistance remain significant hurdles in treating patients with mantle cell lymphoma (MCL). The Lymphoma Research Foundation's 2023 MCL Scientific Consortium and Workshop addressed these complexities, aiming to dissect the intricate biology of MCL and propel progress towards a cure.

 spoke with leaders in the MCL field to better understand the aim of the consortium and the advancements they hope to see in the space. The journal 

published these findings in the February 2024 issue. The interviews included Elias Campo, MD, PhD, research director and professor of anatomic pathology at the Hospital Clinic of the University of Barcelona; Michael Wang, MD, professor in the Department of Lymphoma and Myeloma at The University of Texas, MD Anderson Cancer Center; Martin Dreyling, MD, PhD, professor of Medicine in the Department of Medicine and head of the Medical Clinic 3 at the University of Munich-Grosshadern in Germany; and Julie M. Vose, MD, MBA, Neumann M. and Mildred E. Harris Professor and division chief in the Division of Hematology at the University of Nebraska Medical Center and coeditor in chief of 

The consortium touched on t(11;14), which dysregulates cyclin D1 and fuels uncontrolled cell growth. Additionally, research presented at the consortium revealed other molecular pathways contributing to treatment resistance and relapse, highlighting the heterogeneous nature of the disease. This heterogeneity underscored the need for personalized treatment strategies and biomarker-based prognostics, a notion further emphasized by multiple findings on the predictive value of specific gene mutations.

Beyond understanding the inner workings of MCL, presentations also focused on novel therapeutic avenues. Specifically, there were encouraging data on the potential of next-generation BTK inhibitors including acalabrutinib (Calquence) to overcome resistance.

Challenges such as the limitations of current risk stratification models remain, underscoring the need for robust biomarkers to guide early interventions and optimize treatment selection. Additionally, the consortium featured a discussion on addressing a lack of diversity in clinical trial populations, which may help increase treatment access for those with various medical conditions.

“…The patient population that has a disease is not always [represented] in the clinical trials. That’s why it’s important to be able to have a diversity of patients in clinical trials: to test these new therapies because [patients] may have other medical conditions that would change the outcome of trials and not be necessarily representative of the entire patient population with that disease,” Vose said. “It’s important to try to advance the treatment of a very diverse patient population through these clinical trial mechanisms.”

The Lymphoma Research Foundation MCL Scientific Consortium and Workshop focused on relevant topics that can help clinicians personalize treatment for patients. 

Unraveling Resistance and Heterogeneity in Mantle Cell Lymphoma Management

 video series, Bruce Cheson, MD, FACP, FAAAS, FASCO, a board certified hematologist at the Center for Cancer and Blood Disorders in Bethesda, Maryland, spoke with Steven Park, MD, an oncologist and vice chair of Research at the Atrium Health Levine Cancer Institute and a clinical professor of Medicine at Wake Forest University. These experts shared their insight on the phase 1/2 E7438-G000-101 (NCT01897571) clinical trial and highlighted key data on tazemetostat (Tazverik), an EZH2 inhibitor, in relapsed or refractory follicular lymphoma.

In the video series, Cheson and Park discussed the following:

Overview of relapsed/refractory follicular lymphoma and available treatment options

Tazemetostat trial data and propensity score-matched analysis

Role of tazemetostat treatment moving forward

Don’t forget to subscribe to the “Oncology Peer Review On-The-Go” podcast on 

Expert oncologist/hematologists Bruce Cheson, MD, FACP, and Steven Park, MD, discuss findings from the E7438-G000-101 trial and consider the efficacy of tazemetostat as treatment for relapsed or refractory follicular lymphoma.

Between the Lines Podcast: Tazemetostat in Relapsed/Refractory Follicular Lymphoma

Robert Stuver, MD, and Zachary D. Epstein-Peterson, MD, both of the Lymphoma Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center in New York, spoke with CancerNetwork® about their review published in the journal 

Current Treatment of Peripheral T-cell Lymphoma

In the article, Stuver and Epstein-Peterson explored current approaches to the diagnosis and treatment of peripheral T-cell lymphoma and novel emerging strategies clinicians who are practicing in the community should be aware of.

Robert Stuver, MD, and Zachary D. Epstein-Peterson, MD, spoke with CancerNetwork® about a review article on the treatment of peripheral T-cell lymphoma published in the journal ONCOLOGY®.

Oncology Peer Review On-The-Go: Current Treatments in Peripheral T-cell Lymphoma

Juan Pablo Alderuccio, MD, assistant professor of Medicine in the Division of Hematology, Department of Medicine at the Sylvester Comprehensive Cancer Center of the University of Miami Miller School of Medicine in Florida, spoke with CancerNetwork

 about his review published in the journal 

Current Treatments in Marginal Zone Lymphoma

In the article, Alderuccio explored current approaches to the diagnosis and treatment of marginal zone lymphoma. He also touched on his strategies for treating localized vs advanced disease and novel emerging strategies clinicians who are practicing in the community should be aware of.

Juan Pablo Alderuccio, MD, spoke with CancerNetwork® about a review article on the treatment of marginal zone lymphoma published in the journal ONCOLOGY®.

Oncology Peer Review On-The-Go: Current Treatments in Marginal Zone Lymphoma

Kirk E. Cahill, MD, and Sonali M. Smith, MD

both of the Department of Medicine, Section of Hematology/Oncology at the University of Chicago Medicine Comprehensive Cancer Center in Chicago, Illinois, spoke about their manuscript titled, ‘

Follicular Lymphoma: a Focus on Current and Emerging Therapies

,’ that was recently published in the journal 

In the review, the authors explore current approaches to the diagnosis and treatment of follicular lymphoma, with a focus on emerging investigational therapies and novel combination strategies. Some areas of unmet need they touch on in the paper include precision approaches to individual patients, trial end points with quality-of-life measures, and guidance for sequencing of available regimens and agents.

Kirk E. Cahill, MD, and Sonali M. Smith, MD, spoke with CancerNetwork® about their review of the current management and treatment of follicular lymphoma published in the journal ONCOLOGY®.

Oncology Peer Review On-The-Go: Focus of Current and Emerging Therapies in Follicular Lymphoma 

The CD19 t-haNK therapy alone and in combination with rituximab achieved complete responses and no significant toxicities in 2 patients with late-stage WM.

Novel CD19 CAR-NK Therapy Yields Responses in Waldenstrom Macroglobulinemia

Jose Sandoval Sus, MD, discussed the “revolution” that CAR T-cell therapies have facilitated for patients with large B-cell lymphomas.

Considerations for CAR T Use Across Large B-Cell Lymphoma Variants

Preplanned interim results from the phase 3 EPCORE FL-1 trial support the FDA granting priority review to epcoritamab with rituximab and lenalidomide in relapsed/refractory FL. 

SC Epcoritamab Combo Meets ORR/PFS End Points in R/R Follicular Lymphoma

The anti-CD19/4-1BB CAR T-cell therapy candidate elicited an ORR and CR rate of 100% each in patients with relapsed/refractory MCL. 

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