Case 3: Relapsed/Refractory Follicular Lymphoma in the Third Line and Beyond
This is Part 3 of Relapsed/Refractory Follicular Lymphoma: Choosing the Right Regimen for the Right Patient, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Loretta Nastoupil, Carla Casulo, and Kami Maddocks discuss treatment options for relapsed/refractory high-risk follicular lymphoma in the third line and beyond. The patient is the 62-year-old fit male from Case 1 who, following front-line bendamustine/rituximab and a second-line anthracycline-based regimen, achieves only a partial response with persistent disease on PET. His disease subsequently progresses—presenting the faculty with the challenge of selecting a third-line approach for a young, heavily pretreated patient with high-risk disease characteristics. The faculty explore the role of rebiopsy at each relapse to rule out transformation, particularly in patients with persistent FDG-avid disease after multiple lines of chemoimmunotherapy. They discuss the available third-line options—including single-agent bispecific antibodies, bispecific-based triplet regimens, CAR-T cell therapy, and novel oral combinations—and how patient preferences and disease biology inform sequencing decisions. They also address the importance of infection mitigation strategies, including antimicrobial prophylaxis and IVIG replacement, given the cumulative immunosuppression seen in heavily pretreated patients.
Case 2: Follicular Lymphoma With Relapse After Rituximab Monotherapy
This is Part 2 of Relapsed/Refractory Follicular Lymphoma: Choosing the Right Regimen for the Right Patient, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Loretta Nastoupil, Carla Casulo, and Kami Maddocks discuss the management of follicular lymphoma that has relapsed after rituximab monotherapy. The patient is a 72-year-old woman with hypertension and controlled type 2 diabetes who initially presented with symptomatic anemia and stage IV, low-tumor-burden follicular lymphoma, achieved a response to single-agent rituximab. She now returns 6 years later at age 78 with fatigue, mild thrombocytopenia, recurrent anemia, and small-volume adenopathy, with a strong preference for maintaining her quality of life and daily activities. The faculty explore how patient age, comorbidities, remission duration, and treatment goals should guide second-line therapy selection in older adults with indolent follicular lymphoma. They discuss the rationale for retreatment with single-agent CD20-directed antibody therapy vs more intensive triplet regimens, and address the evolving role of bispecific antibodies and clinical trials in this setting, as well as when chemoimmunotherapy may still be appropriate for patients requiring rapid disease control.
Case 1: Early Relapsed Follicular Lymphoma
This is Part 1 of Relapsed/Refractory Follicular Lymphoma: Choosing the Right Regimen for the Right Patient, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Loretta Nastoupil, Carla Casulo, and Kami Maddocks discuss the management of relapsed/refractory follicular lymphoma after first and early relapse. The patient is a fit, 62-year-old man with no comorbid conditions who was diagnosed with advanced-stage, low-grade follicular lymphoma (FLIPI 4) and achieved a complete response to front-line bendamustine/rituximab. Approximately 2 years later, he returns with symptomatic relapse, high disease burden, and extranodal involvement confirmed on biopsy. The faculty explore the prognostic significance of progression within 24 months of front-line chemoimmunotherapy and the importance of rebiopsy to rule out transformation to large cell lymphoma. They discuss the emerging role of novel triplet regimens—specifically lenalidomide/rituximab combined with either tafasitamab or epcoritamab—as preferred options over chemotherapy in this setting. They also compare practical and logistical considerations for choosing between these two regimens, including administration route, visit burden, toxicity profiles, and biomarkers such as CD20 expression.
Study Finds DLBCL Subtype May Have Higher Mortality Risk in Female Patients
An international research team has shown that a specific subtype of diffuse large B-cell lymphoma (DLBCL) is associated with higher mortality risk in women than in men. The study was led by the laboratory of Ari Melnick, MD, Director of the Josep Carreras Leukaemia Research Institute and the Gebroe ...
Sonrotoclax Receives Accelerated Approval in Relapsed or Refractory MCL
On May 13, the U.S. Food and Drug Administration (FDA) granted accelerated approval to sonrotoclax (Beqalzi), a BCL-2 inhibitor, for adults with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor....
Inherited Long Telomeres May Increase the Risk of Lymphoid Cancers
Researchers at the Johns Hopkins Kimmel Cancer Center and the Telomere Clinic at Johns Hopkins have identified a genetic syndrome in which unusually long telomeres—the protective caps at the ends of chromosomes—allow immune cells to remain biologically “younger” for longer than normal, predisposing ...
Integrated Molecular Analysis Identifies Determinants of Outcomes in TP53-Mutated DLBCL
In a study reported in the Journal of Clinical Oncology, Uppal et al identified factors associated with poorer outcomes in patients with TP53-mutated diffuse large B-cell lymphoma (DLBCL). Study Details The analysis included clinical and molecular data from 3,091 individuals which was derived from...
Four-Drug Regimen Induces High Complete Response Rate in Early-Stage Classical Hodgkin Lymphoma
High objective response and complete response rates were observed with treatment with brentuximab vedotin and nivolumab in combination with doxorubicin and dacarbazine chemotherapy in patients with early-stage classical Hodgkin lymphoma, according to the results of a phase II trial published in...
Lenalidomide Plus Rituximab in Relapsed or Refractory Indolent Non-Hodgkin Lymphoma: 5-Year Follow-up From AUGMENT
As reported in the Journal of Clinical Oncology by Leonard et al, the 5-year follow-up of the phase III AUGMENT trial has shown continued benefit of lenalidomide plus rituximab (R2) vs rituximab with placebo (R-placebo) in patients with relapsed or refractory indolent non-Hodgkin lymphoma. Study...
Metabolic Tumor Volume Predicts CAR T-Cell Therapy Response in LBCL
Positron-emission tomography (PET)-based metabolic tumor volume could serve as a significant measure of response to chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma, according to the results of a study published in The Journal of Nuclear Medicine. Metabolic...
Bispecific Antibody Shows Deep Remission in Patients With Relapsed/Refractory Follicular Lymphoma
A population of patients with highly refractory follicular lymphoma achieved long-standing responses with few significant adverse events from odronextamab monotherapy, according to findings of the ELM-2 study. The study outcomes were published by Tessoulin et al in Clinical Lymphoma, Myeloma &...
FDA Grants Traditional Approval to Brexucabtagene Autoleucel for Relapsed or Refractory MCL
The U.S. Food and Drug Administration (FDA) has granted traditional approval to the chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel (Tecartus) for adult patients with relapsed or refractory mantle cell lymphoma (MCL). The full approval now includes efficacy, safety, and...
FDA Approves Chemoimmunotherapy Regimen for Hodgkin Lymphoma
On March 20, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo) with doxorubicin, vinblastine, and dacarbazine (AVD) for adult and pediatric patients aged 12 years and older with previously untreated stage III or IV classical Hodgkin lymphoma. The FDA also granted traditional...
Early Study Evaluates Two-Vaccine Strategy in T-Cell Lymphoma
T-cell lymphomas are notoriously difficult to treat because immunotherapy, despite being one of the most effective therapies for treating cancer, can’t easily distinguish cancerous T cells from healthy ones. Now, scientists at The Wistar Institute have designed a two-vaccine approach that not only...
Lisocabtagene Maraleucel in Relapsed or Refractory MZL
In a phase II trial (TRANSCEND FL) reported in The Lancet, Palomba et al found that the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel was active in patients with relapsed or refractory marginal zone lymphoma (MZL). Study Details In the international multicenter trial, 67...
Dietary Influence on Leukemia and Lymphoma Progression
In 2015, LH, a 66-year-old female, was diagnosed with chronic lymphocytic leukemia (CLL), Rai stage 0. Untreated, the woman’s lymphocyte count rose from 5,000/mm3 to 16,000/mm3 in 6 years (doubling time = 4.2 years). She was then advised to stop eating red meat (see the figure). Commercially...
Fifteen-Year Results From SWOG S0016 Suggest Follicular Lymphoma May Be Curable
Advanced-stage follicular lymphoma is currently considered incurable. But a new analysis of long-term data from patients treated for the disease years ago with standard regimens of immunotherapy and a chemotherapy combination known as CHOP suggests that many of those patients can now be considered...
First Results of Phase III OLYMPIA-3: Odronextamab Plus CHOP in Untreated DLBCL
The bispecific antibody odronextamab plus standard CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) chemotherapy yielded robust and durable responses in treatment-naive patients with diffuse large B-cell lymphoma (DLBCL), based on the first results of the phase III OLYMPIA-3 study...
CLL/SLL: FDA Approves Combination of Acalabrutinib and Venetoclax
On February 19, the U.S. Food and Drug Administration (FDA) approved the Bruton’s tyrosine kinase inhibitor acalabrutinib (Calquence) tablets and capsules in combination with the BCL2 inhibitor venetoclax (Venclexta) for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma...
Epcoritamab Plus R2 in Follicular Lymphoma: A Potential New Treatment Standard
In patients with follicular lymphoma who received at least one prior line of therapy, the combination of the bispecific antibody epcoritamab-bysp and rituximab–lenalidomide (R2) reduced the risk of disease progression or death by almost 80% over R2 alone, based on the primary analysis of the phase...
Case 3: Management of Multiply Relapsed DLBCL
This is Part 3 of Personalizing Treatment Pathways in Relapsed/Refractory DLBCL, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Jeremy Abramson, J. Erika Haydu, and Jacob Soumerai discuss the treatment of multiply relapsed diffuse large B-cell lymphoma (DLBCL). The patient is a 44-year-old man with stage IV, IPI 2, GCB-subtype, MYC/BCL2 double-hit lymphoma who achieved complete remission with front-line dose-adjusted EPOCH-R but relapsed at 18 months. As a young, transplant-eligible patient, he received R-DHAP with the goal of proceeding to autologous stem cell transplant. However, he progressed after two cycles with worsening hepatic dysfunction. In the conversation that follows, the faculty discuss age-based treatment selection for late relapse, the importance of monitoring for cytokine-release syndrome and immune effector cell–associated neurotoxicity, and treatment options after failure of CAR T-cell therapy—especially in the case of antigen loss.
Case 2: Second-Line Management of Relapsed DLBCL
This is Part 2 of Personalizing Treatment Pathways in Relapsed/Refractory DLBCL, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Jeremy Abramson, J. Erika Haydu, and Jacob Soumerai discuss the second-line treatment of relapsed diffuse large B-cell lymphoma (DLBCL). The patient is a 74-year-old woman with stage IV, IPI 4, non-GCB subtype DLBCL who achieved complete remission with front-line Pola-R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone) but relapsed 9 months later with symptomatic peritoneal lymphomatosis. Despite being 75 years old at relapse, she is considered eligible for chimeric antigen receptor (CAR) T-cell therapy, but she faces barriers to accessing this treatment and is interested in other options. In the conversation that follows, the faculty discuss CAR T-cell therapy eligibility in older patients, second-line treatment options for patients without CAR-T access, and treatment sequencing considerations.
Case 1: Management of Early Relapsed DLBCL
This is Part 1 of Personalizing Treatment Pathways in Relapsed/Refractory DLBCL, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Jeremy Abramson, J. Erika Haydu, and Jacob Soumerai discuss the treatment of early relapsed diffuse large B-cell lymphoma. The patient is a 64-year-old woman with stage III, IPI 3, GCB-subtype DLBCL who developed primary refractory disease after R-CHOP therapy, with mixed/progressive findings on interim PET/CT after three cycles. Despite being relatively asymptomatic with an ECOG performance status of 1, confirmatory biopsy demonstrated persistent GCB DLBCL. In the conversation that follows, the faculty discuss the use of CAR T-cell therapy in the second-line treatment of DLBCL, bridging therapy considerations, and the management of cytokine-release syndrome.
Pirtobrutinib Improves Progression-Free Survival vs Bendamustine/Rituximab in Front-Line CLL/SLL
The first prospective, randomized phase III trial of a noncovalent Bruton’s tyrosine kinase (BTK) inhibitor exclusively in treatment-naive patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)—BRUIN CLL-313—demonstrated a statistically significant and clinically...
Phased Variant ctDNA as Biomarker After First-Line Treatment in LBCL
In a study (DIRECT) reported in the Journal of Clinical Oncology, Krupka et al found that phased variant (PV) ctDNA provided “sensitive and clinically meaningful response assessment” after first-line treatment of large B-cell lymphoma (LBCL). As stated by the investigators, “Tracking tumor-specific ...
Nivolumab Plus AVD Reduces Disease Progression Risk in Adolescents With Advanced Classical Hodgkin Lymphoma
A combination of nivolumab with AVD chemotherapy (doxorubicin, vinblastine, and dacarbazine) demonstrated a significant reduction in the risk of disease progression or death compared with brentuximab vedotin plus AVD in adolescent patients with newly diagnosed advanced classical Hodgkin lymphoma,...
Refractory LBCL: CD19-Targeting CAR T-Cell Therapy Plus Rituximab
A dual-antigen targeting combination of the CD19-targeting chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel plus the CD20-targeting agent rituximab led to durable responses and reduced relapses in patients with refractory large B-cell lymphoma (LBCL), according to findings...
Addition of Epcoritamab to Lenalidomide Plus Rituximab in Relapsed or Refractory Follicular Lymphoma
As reported in The Lancet by Falchi et al, an interim analysis of the phase III EPCORE FL-1 trial has shown that the addition of the bispecific antibody epcoritamab (for B-cell CD20 and T-cell CD3 antigens) to lenalidomide plus rituximab improved the objective response rate and progression-free...
Addition of Tafasitamab to Lenalidomide Plus Rituximab in Relapsed or Refractory Follicular Lymphoma
In a phase III trial (inMIND) reported in The Lancet, Sehn et al found that the addition of the CD19-targeted Fc-enhanced monoclonal antibody tafasitamab to lenalidomide plus rituximab improved progression-free survival in patients with relapsed or refractory follicular lymphoma. Study Details In...
Lymphocyte Kinetics After CAR T-Cell Infusion May Predict Survival Outcomes in Non-Hodgkin Lymphoma
A higher absolute lymphocyte count (ALC) after receipt of chimeric antigen receptor (CAR) T-cell therapy may be associated with improved progression-free and/or overall survival in patients with non-Hodgkin lymphoma, according to findings from the 2025 American Society of Hematology (ASH) Annual...
FLIPI24: New Prognostic Model for Newly Diagnosed Follicular Lymphoma
As reported in the Journal of Clinical Oncology, Maurer et al have developed FLIPI24, a modern prognostic model for newly diagnosed follicular lymphoma. As stated by the investigators, “Although most patients with … [follicular lymphoma] can expect an indolent course, progressive lymphoma remains...
Follicular Lymphoma: Durable Remissions and Sustained Safety With Third-Line Lisocabtagene Maraleucel
Patients with relapsed or refractory follicular lymphoma treated in the third-line setting with a single infusion of the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel continued to show responses after 3 years, according to long-term follow-up results from the TRANSCEND FL...
CD40 Overexpression Emerges as a Potential Biomarker for Angioimmunoblastic T-Cell Lymphoma
Researchers at The University of Texas MD Anderson Cancer Center have identified CD40 overexpression as a potential prognostic biomarker in angioimmunoblastic T-cell lymphoma (AITL), a rare subtype of non-Hodgkin lymphoma that is difficult to diagnose and treat. The results of their study were...
Noninferiority Shown for Pirtobrutinib vs Ibrutinib in CLL/SLL
The noncovalent Bruton's tyrosine kinase (BTK) inhibitor pirtobrutinib achieved noninferiority to the covalent BTK inhibitor ibrutinib in terms of overall response rate in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to findings from a randomized...
Epcoritamab Added to Second-Line Lenalidomide/Rituximab Improves Responses in Follicular Lymphoma
When epcoritamab was added to lenalidomide and rituximab, response rates were significantly higher and progression-free survival was prolonged for patients with follicular lymphoma treated in the second-line setting or beyond, according to findings from the phase III EPCORE FL-1 trial presented at...
FDA Approves CAR T-Cell Therapy for Relapsed/Refractory Marginal Zone Lymphoma
On December 4, 2025, the U.S. Food and Drug Administration (FDA) approved the CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (Breyanzi) for the treatment of adult patients with relapsed or refractory marginal zone lymphoma who have received at least two prior...
Tisagenlecleucel in Relapsed or Refractory Large B-Cell Lymphoma: 5-Year Outcomes From the JULIET Trial
As reported in the Journal of Clinical Oncology by Maziarz et al, 5-year analysis of the pivotal phase II JULIET trial has shown maintained efficacy of tisagenlecleucel in patients with relapsed or refractory large B-cell lymphoma. Study Details In the trial, 115 patients received tisagenlecleucel...
FDA Approves Epcoritamab for Two Follicular Lymphoma Indications
On November 18, 2025, the U.S. Food and Drug Administration (FDA) approved epcoritamab-bysp (Epkinly), a bispecific CD20-directed CD3 T-cell engager, in combination with lenalidomide and rituximab for the treatment of patients with relapsed or refractory follicular lymphoma. In addition, the FDA...
Immunotherapy Combination Active in Patients With Large B-Cell Lymphoma Who Are Not Eligible for Autologous Stem Cell Transplant
In the global phase III SUNMO trial, the combination of a bispecific antibody and an antibody-drug conjugate was compared with rituximab plus gemcitabine and oxaliplatin (GemOx) in the treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL) who were ineligible for autologous...
Axicabtagene Ciloleucel in Relapsed or Refractory Indolent Non-Hodgkin Lymphoma: 5-Year Follow-up of ZUMA-5
As reported in the Journal of Clinical Oncology by Neelapu et al, the 5-year follow-up of the phase II ZUMA-5 trial has shown sustained responses with axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory indolent non-Hodgkin lymphoma. Study Details In the single-arm,...
My 50 Years in Lymphoma: Lessons Learned?
In the 50 years now since my fellowship training, there have been major advances in the diagnosis, staging, prognostic scoring, treatment, and response assessment of lymphomas. To conjure up the future, we must first appreciate the present by understanding how it arose from the past.1 So, a trip in ...
Glofitamab Plus Polatuzumab Vedotin in Relapsed or Refractory Large B-Cell Lymphoma
In a phase Ib/II trial reported in the Journal of Clinical Oncology, Hutchings et al found that the combination of glofitamab and polatuzumab vedotin was associated with high activity in patients with relapsed or refractory large B-cell lymphoma, including high-grade B-cell lymphoma. Study Details...
Cognitive Function and Statin Administration During Doxorubicin-Based Cancer Treatment
Contrary to previous research, a preplanned secondary analysis of the multicenter PREVENT trial, reported by W.Gregory Hundley, MD, FACC, of Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, and colleagues in ...
Cutaneous T-Cell Lymphoma: Use of Durvalumab Alone or With Lenalidomide Under Study in Phase II Trial
In a randomized phase II trial, Christiane Querfeld, MD, PhD, and colleagues investigated the effects of a PD-L1–blocking strategy for targeting both the innate and adaptive immune systems in cutaneous T-cell lymphoma (CTCL). At the 2025 Society of Hematologic Oncology (SOHO) Annual Meeting,1 Dr....
Chemotherapy-Free Regimen vs Standard Immunochemotherapy in Mantle Cell Lymphoma in Older Patients
In a phase II/III study (ENRICH) reported in The Lancet, Lewis et al found that the chemotherapy-free combination of ibrutinib plus rituximab prolonged progression-free survival vs standard immunochemotherapy in patients aged 60 years or older with previously untreated mantle cell lymphoma. Study...
Combination Therapies for Diffuse Large B-Cell Lymphoma: 5-Year Outcomes of the POLARIX Trial
As reported in the Journal of Clinical Oncology by Morschhauser et al, the 5-year findings of the POLARIX trial showed a continued benefit with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs rituximab, cyclophosphamide, doxorubicin, vincristine,...
EHA Publishes Guidelines for LBCL and Multiple Myeloma
The European Hematology Association (EHA) has published two new sets of clinical practice guidelines, including its first dedicated guidelines for large B-cell lymphoma (LBCL), which was published in HemaSphere, as well as an updated set of guidelines in collaboration with the European Myeloma...
Rare Secondary Cancer After CAR T-Cell Therapy Successfully Treated, Case Report Shows
In a case presentation published in The New England Journal of Medicine, targeted treatment was successful for chimeric antigen receptor (CAR)-positive peripheral T-cell lymphoma developed after CAR T-cell therapy for multiple myeloma. Using advanced genomic, phenotypic, and functional profiling...
Emerging PD-1 Inhibitor Plus Chemotherapy Shows Efficacy in Second-Line Classical Hodgkin Lymphoma
The addition of the PD-1 inhibitor sintilimab to ICE (ifosfamide, carboplatin, and etoposide) chemotherapy appeared to significantly improve the complete remission rate and showed a trend toward improved progression-free survival in second-line classical Hodgkin lymphoma, according to Yuankai Shi,...
Tafasitamab Combined With Lenalidomide and Rituximab Improved Outcomes in Relapsed or Refractory Follicular Lymphoma
Adding tafasitamab-cxix, an anti-CD19 monoclonal antibody, to lenalidomide and rituximab significantly prolonged progression-free survival in patients with relapsed or refractory follicular lymphoma, according to data presented at the 2025 European Hematology Association (EHA) Congress.1 Results...
