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This is Part 3 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss the third-line treatment of chronic lymphocytic leukemia (CLL). The patient in question originally presented with CLL with a white blood cell (WBC) count of 13 x 109/L and normal hemoglobin and platelets. She was observed for 4 years and then developed progressive disease with weight loss, splenomegaly, and lymphadenopathy. At this point, her WBC was 220 x 109/L, her hemoglobin was 9.4, and her platelet count was 102,000. Sequencing revealed unmutated IGHV, TP53 wildtype, deletion 13q, and trisomy 12. She was initially treated with acalabrutinib for 4 years but developed progressive disease, and then received venetoclax and rituximab for 2 years. She was monitored but developed progressive disease approximately 30 months off therapy, at age 74 years. In the conversation that follows, the faculty discuss potential third-line treatment options for this patient, whether she would be a candidate for CAR T-cell therapy if she were younger, whether venetoclax re-treatment would be an option, and more.
This is Part 2 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss second-line treatment strategies for chronic lymphocytic leukemia (CLL). The patient is a 71-year-old man who presented in 2014 with symptomatic CLL after being monitored for 4 years. He then developed progressive fatigue, organomegaly, and bulky lymph nodes. Sequencing revealed unmutated IGHV and deletion 11q. He was initially treated with ibrutinib at 420 mg daily and then developed progressive disease after 5 years. In the conversation that follows, the faculty discuss how they would approach treatment sequencing in later lines of therapy, whether it is necessary to test for BTK inhibitor resistance, how their treatment recommendations might change if the patient’s cytogenetic profile evolved, and more.
This is Part 1 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. To set the stage, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss front-line treatment strategies for chronic lymphocytic leukemia (CLL). The patient is a 71-year-old man who presented in 2020 with symptomatic CLL after he was monitored for a period of 4 years. He developed progressive fatigue, weight loss, splenomegaly, and bulky lymphadenopathy. He has a good performance status and adequate renal function. He has a white blood cell count of 113 x 109/L, hemoglobin of 10.3 g/dL, and a platelet count of 105,000/µL. Sequencing reveals deletion 13q, trisomy 12, unmutated IGHV, and TP53 wild-type. In the conversation that follows, the faculty discuss the patient’s prognosis, how comorbidities impact treatment options, time-limited vs continuous therapy, and more.
In a single-center phase I/II study reported in the Journal of Clinical Oncology, Shah et al found that adaptive manufactured lentiviral anti-CD20/anti-CD19 (LV20.19) chimeric antigen receptor (CAR) T-cell treatment was highly active in relapsed or refractory mantle cell lymphoma. Study Details In...
In a UK phase III trial (UKALL 2011) reported in the Journal of Clinical Oncology, Kirkwood et al found that a shorter duration of induction dexamethasone did not reduce steroid-related toxicity and that high-dose methotrexate (HDM) did not reduce central nervous system (CNS) relapse among patients ...
A novel cell therapy approach using cord blood–derived natural killer (NK) cells precomplexed with the CD30/CD16A bispecific antibody AFM13 may be safe and generate responses in patients with refractory CD30-positive lymphomas, according to a recent study published by Nieto et al in Nature...
“Care more particularly for the individual patient than for the special features of the disease.” —Sir William Osler Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common leukemia in the Western hemisphere. The majority of patients who require treatment are older than ...
In the phase III JCOG1411/FLORA trial of patients with untreated advanced-stage, very low–tumor burden follicular lymphoma, rituximab induction delayed disease progression to high–tumor burden follicular lymphoma and delayed the initiation of cytotoxic chemotherapy, according to Japanese...
The addition of tafasitamab, a CD19 monoclonal antibody, to the commonly used lenalidomide and rituximab backbone significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma, according to data presented during the 2024 American Society of Hematology...
The U.S. Food and Drug Administration (FDA) has approved brentuximab vedotin (Adcetris) in combination with lenalidomide and a rituximab product for adults with relapsed or refractory large B-cell lymphoma (LBCL)—including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising ...
Autologous stem cell transplantation (ASCT) does not improve survival outcomes for patients with mantle cell lymphoma who achieve a deep first complete remission with undetectable measurable residual disease (MRD) after induction therapy, according to data presented during the 2024 American Society ...
Skin cancers and lymphoma may be more prevalent among individuals with tattoos compared with those without tattoos, according to a recent study published by Clemmensen et al in BMC Public Health. Prior research has shown that tattoo ink does not just remain at the site of injection—instead, when...
This is Part 3 of Evolving Treatment Landscape of Indolent Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Laurie Sehn, Gilles Salles, and Sonali Smith discuss the treatment of relapsed/refractory nodal marginal zone lymphoma. The patient is a 68-year-old man who was diagnosed with marginal zone lymphoma in 2019 after a PET/CT scan found a large pelvic mass involving the bladder and causing left-sided hydronephrosis; SUVmax was 7, and LDH was normal. He received bendamustine plus rituximab for six cycles, achieving a complete response on PET. In 2023, surveillance CT showed a recurrent pelvic mass and several mesenteric lymph nodes; PET/CT showed no additional disease, and the SUVmax was 6. In the conversation that follows, the faculty discuss whether transformation is a concern in marginal zone lymphoma, the role of BTK inhibitors, and whether CAR T-cell therapy could be an option for this patient.
This is Part 2 of Evolving Treatment Landscape of Indolent Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Laurie Sehn, Gilles Salles, and Sonali Smith discuss the third-line treatment of relapsed/refractory follicular lymphoma. The patient is a 74-year-old woman who originally presented in 2014 with asymptomatic low-bulk stage IVA follicular lymphoma, grade 1 to 2, for which she received four cycles of rituximab. In 2019, she developed symptomatic disease, with multiple nodes > 7 cm, and received bendamustine plus rituximab for six cycles, achieving a complete response. In December 2024, she presents with fatigue, progressive lymphadenopathy above and below the diaphragm, no B-symptoms, normal LDH, and SUVmax of 10. In the conversation that follows, the faculty discuss next steps for this patient, whether there are any actionable biomarkers for follicular lymphoma, and patient-specific factors to consider when selecting treatment in the third-line setting.
This is Part 1 of Evolving Treatment Landscape of Indolent Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Laurie Sehn, Gilles Salles, and Sonali Smith discuss the second-line treatment of early relapsing follicular lymphoma. The patient is a 41-year-old man originally diagnosed with grade 1 to 2 follicular lymphoma in 2023. He received bendamustine plus rituximab for six cycles, achieving a complete response on PET, and then started rituximab maintenance. After four cycles, he developed shortness of breath on exertion and night sweats. PET/CT confirmed recurrence of lymphadenopathy above and below the diaphragm, as well as a pleural-based mass (SUVmax of 16), pleural effusion, and peritoneal deposits; his LDH was normal. In the conversation that follows, the faculty discuss the clinical implications of progression-of-disease within 24 months in follicular lymphoma, the importance of ruling out transformation, and the role of novel therapies at disease relapse.
In a single-institution phase I study reported in the Journal of Clinical Oncology, Jae H. Park, MD, and colleagues found that first-in-human use of a CD19-1XX chimeric antigen receptor (CAR) T-cell therapy with calibrated signaling showed high activity in patients with relapsed or refractory large ...
“Care more particularly for the individual patient than for the special features of the disease.”—Sir William Osler Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common leukemia in the Western hemisphere. The majority of patients who require treatment are older than ...
As reported in The Lancet Oncology by Michael Wang, MD, and colleagues, the phase III SYMPATICO trial has shown that venetoclax/ibrutinib significantly improved progression-free survival vs placebo/ibrutinib in patients with relapsed or refractory mantle cell lymphoma (MCL). Study Details In the...
ZUMA-2 is a single-arm, multicenter, open-label phase II study that investigated leukapheresed adults with mantle cell lymphoma whose disease was refractory to or had relapsed after up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy; anti-CD20...
The U.S. Food and Drug Administration (FDA) has approved brentuximab vedotin (Adcetris) in combination with lenalidomide and a rituximab product for adult patients with relapsed or refractory large B-cell lymphoma (LBCL)—including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL ...
First-line treatment with the Bruton’s tyrosine kinase inhibitor zanubrutinib plus the anti-CD20 monoclonal antibody obinutuzumab and the BCL2 inhibitor venetoclax appeared to be safe and active in previously untreated patients with TP53-mutated mantle cell lymphoma, based on the results of the...
Late relapse of diffuse large B-cell lymphoma (DLBCL) may represent a new lymphoma arising from a common precursor cell that is essentially chemotherapy-naive. Treatment with curative intent using a second-line regimen like R-CHOP (rituximab cyclophosphamide, doxorubicin, prednisone, and...
“It isn’t the mountains ahead to climb that wear you out; it’s the pebble in your shoe.” —Muhammad Ali Long-term survival in early-stage classic Hodgkin lymphoma (cHL) was first made possible by the introduction of the mantle and inverted Y fields of radiotherapy in the 1960s. The addition of...
On January 16, the U.S. Food and Drug Administration (FDA) granted traditional approval to the Bruton’s tyrosine kinase inhibitor acalabrutinib (Calquence) with bendamustine and rituximab for adults with previously untreated mantle cell lymphoma who are ineligible for autologous hematopoietic stem...
As reported in JAMA Oncology by Daw et al, findings in a cohort of the phase II CheckMate 744 trial indicated good outcomes with a response-adapted, transplantation-free treatment approach in children and adolescents and young adults (AYAs) with low-risk relapsed classical Hodgkin lymphoma (HL)....
In an interim analysis of a phase III trial (ECHELON-3) reported in the Journal of Clinical Oncology, Bartlett et al found that the addition of brentuximab vedotin (BV) to lenalidomide and rituximab improved overall survival in patients with relapsed or refractory diffuse large B-cell lymphoma...
In a registrational trial reported in the Journal of Clinical Oncology, Foss et al found that denileukin diftitox (DD)-cxdl—a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2—was active in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL)....
In a phase I/II trial reported in the Journal of Clinical Oncology, Torka et al found that the addition of nivolumab to standard doxorubicin, vinblastine, and dacarbazine (N-AVD) was “highly effective” as front-line treatment for patients aged ≥ 60 with classical Hodgkin lymphoma. Study Details In...
A primary analysis of ZUMA-2, reported at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, demonstrated durable responses to brexucabtagene autoleucel in patients with Bruton’s tyrosine kinase (BTK) inhibitor–naive mantle cell lymphoma. The findings from cohort 3 of...
As reported in the Journal of Clinical Oncology by Shadman et al, 5-year follow-up of the phase III SEQUOIA trial demonstrated that zanubrutinib continued to show a progression-free survival benefit over bendamustine plus rituximab in previously untreated patients with chronic lymphocytic...
In a phase I dose-escalation study (COBALT-LYM) reported in The Lancet Oncology, Iyer et al found that CTX130 (volamcabtagene durzigedleucel)—a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells—had a manageable safety profile and showed...
Researchers may have discovered a factor contributing to cancer cell evasion of chimeric antigen receptor (CAR) T-cell therapy, according to a recent study published by Chen et al in Cell. The findings could lead to more personalized therapies that improve survival among patients with cancer....
Researchers have revealed that high-dose chemotherapy followed by autologous stem cell transplantation may not benefit patients with mantle cell lymphoma (MCL) who are in remission following initial treatment, according to new findings presented by Fenske et al at the 2024 American Society of...
Researchers have found that the noncovalent Bruton's tyrosine kinase inhibitor (BTK) pirtobrutinib may offer superior progression-free survival in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to recent findings presented by Sharman et al at the 2024...
Timothy S. Fenske, MD, of the Medical College of Wisconsin presented an initial report from the ECOG-ACRIN EA4151 phase III randomized trial exploring outcomes of autologous hematopoietic cell transplantation (ASCT) in mantle cell lymphoma. The researchers randomized patients in first complete remission with undetectable minimal residual disease and found that ASCT was not associated with improved outcomes (Abstract LBA-6).
The antibody loncastuximab tesirine may offer a benefit in patients with high-risk follicular lymphoma and marginal zone lymphoma, according to the findings of two clinical trials presented by Alderuccio et al and Lossos et al at the 2024 American Society of Hematology (ASH) Annual Meeting &...
Findings from a series of studies conducted in mice, human tissues, and healthy volunteers suggest that a ketogenic diet may enhance the effectiveness of chimeric antigen receptor (CAR) T-cell therapy. The results point to β-hydroxybutyrate (BHB), a substance produced when a ketogenic diet is...
Maayan Levy, PhD, and Marco Ruella, MD, of the University of Pennsylvania, Perelman School of Medicine, discuss findings on whether ketogenic diet-derived BHB can be provided as a dietary intervention to augment CAR-T function in multiple cancer models. The results of this study will be translated into a first-in-human clinical trial of BHB-supplementation during CAR-T 19 treatment for relapsed or refractory B cell lymphoma. The data were presented during the ASH Plenary Scientific Session (Abstract 4).
As reported in The Lancet by Abramson et al, the phase III STARGLO trial has shown significantly improved overall survival with glofitamab plus gemcitabine/oxaliplatin vs rituximab plus gemcitabine/oxaliplatin in patients with transplant-ineligible relapsed or refractory diffuse large B-cell...
“While clinical trials emphasize improvement in cure rates for patients with advanced classical Hodgkin lymphoma, an important goal is reducing the potential long-term effects of treatment,” commented Iris Isufi, MD, of the Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, and ...
In a phase I study reported in The Lancet Oncology, Maruyama et al found that valemetostat—a novel dual inhibitor of EZH2 and EZH1—showed activity in patients with relapsed or refractory non-Hodgkin lymphoma. Study Details In the study, 90 patients from sites in Japan and the United States were...
I’m 50, just a year older than my father was when he died of colorectal cancer. I was 14 when my dad died, so to me, cancer has always been synonymous with death. From a young age, my brothers and I had a goal: to make sure we packed in enough life before age 50. It never occurred to us that death ...
In a phase II trial (VALENTINE-PTCL01) reported in The Lancet Oncology, Zinzani et al found that valemetostat—a novel dual inhibitor of EZH1 and EZH2—was active in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Study Details In the trial, 133 patients with relapsed or...
Researchers have found that the combination of nivolumab plus doxorubicin, vinblastine, and dacarbazine (AVD) may reduce the risk of cancer progression and mortality in patients with Hodgkin lymphoma compared with standard treatment, according to a recent study published by Herrera et al in The New ...
In an analysis reported in the Journal of Clinical Oncology, Tournilhac et al identified 7-year outcomes of the phase III AATT trial evaluating autologous vs allogeneic transplantation in younger patients with peripheral T-cell lymphoma. Study Details In the trial, 103 patients (aged 18–60) from...
The results from a phase Ib/II study of a five-drug targeted therapy regimen—venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR)—in the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) showed the treatment produced durable remissions and potential...
In a phase II trial (MOLTO) reported in the The Lancet Oncology, Tedeschi et al found that the combination of the PD-L1 blocker atezolizumab, the BCL2 inhibitor venetoclax, and the anti-CD20 antibody obinutuzumab was active in Richter transformation diffuse large B-cell lymphoma (DLBCL-RT). Study...
The U.S. Food and Drug Administration (FDA) has approved a new presentation of bortezomib (Boruzu) for ready-to-use subcutaneous or intravenous administration. This new ready-to-use oncology product reduces the compounding preparation steps typically required with administration. Bortezomib, a...
In two studies recently reported in JACC: CardioOncology, Upshaw and colleagues1 examined the impact of preexisting heart failure on mortality in older patients in the United States with newly diagnosed Hodgkin lymphoma, and Gon and colleagues2 analyzed the incidence and impact of arterial...
On May 15, 2024, lisocabtagene maraleucel (Breyanzi) was granted accelerated approval for adults with relapsed or refractory follicular lymphoma with two or more prior lines of systemic therapy.1 The agent is a CD19-directed genetically modified autologous T-cell immunotherapy. Supporting Efficacy...