Refractory Lymphoma Research Articles

IBCL-335 Mosunetuzumab Monotherapy Continues to Demonstrate Durable Responses in Patients With Relapsed and/or Refractory Follicular Lymphoma After ≥2 Prior Therapies: 3-Year Follow-Up From a Pivotal Phase II Study

IBCL-335 Mosunetuzumab Monotherapy Continues to Demonstrate Durable Responses in Patients With Relapsed and/or Refractory Follicular Lymphoma After ≥2 Prior Therapies: 3-Year Follow-Up From a Pivotal Phase II Study

Epcoritamab + GemOx Induces Deep, Durable Responses in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Updated Results From EPCORE NHL-2

Epcoritamab + GemOx Induces Deep, Durable Responses in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Updated Results From EPCORE NHL-2

Real-World Use of Tafasitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) in the United States by Primary Refractory Status

Real-World Use of Tafasitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) in the United States by Primary Refractory Status

A Budget-Impact (BI) Analysis of Tazemetostat for the Treatment of 3L+ Relapsed or Refractory (R/R) Follicular Lymphoma (FL) in the United States

A Budget-Impact (BI) Analysis of Tazemetostat for the Treatment of 3L+ Relapsed or Refractory (R/R) Follicular Lymphoma (FL) in the United States

Real-World Use of Tafasitamab for Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) in the United States by Age Group (>70 Years and ≤70 Years)

Real-World Use of Tafasitamab for Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) in the United States by Age Group (>70 Years and ≤70 Years)

ABCL-275 Epcoritamab + GemOx Induces Deep Durable Responses in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Updated Results From EPCORE NHL-2

ABCL-275 Epcoritamab + GemOx Induces Deep Durable Responses in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Updated Results From EPCORE NHL-2

Mosunetuzumab With Polatuzumab Vedotin: Subgroup Analyses in Patients (pts) With Primary Refractory or Early Relapsed Large B-Cell Lymphoma (LBCL)

Mosunetuzumab With Polatuzumab Vedotin: Subgroup Analyses in Patients (pts) With Primary Refractory or Early Relapsed Large B-Cell Lymphoma (LBCL)

Sequencing Therapies in Relapsed/ Refractory Large B-cell Lymphoma to Optimize the Chance of Cure

Sequencing Therapies in Relapsed/ Refractory Large B-cell Lymphoma to Optimize the Chance of Cure

Epcoritamab + R-DHAX/C Induces Deep, Durable Responses in Transplant-Eligible Patients With Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL), Including High-Risk Disease

Epcoritamab + R-DHAX/C Induces Deep, Durable Responses in Transplant-Eligible Patients With Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL), Including High-Risk Disease

Extended Follow-Up Beyond 2 .5 Years Demonstrates Long-Term Efficacy in Complete Responders Following Epcoritamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma (R/R LBCL)

Extended Follow-Up Beyond 2 .5 Years Demonstrates Long-Term Efficacy in Complete Responders Following Epcoritamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma (R/R LBCL)

Phase 1 Clinical Trial of LP-284, a Novel Synthetically Lethal Small Molecule, in Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas and Solid Tumors

Phase 1 Clinical Trial of LP-284, a Novel Synthetically Lethal Small Molecule, in Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas and Solid Tumors

Outcome analysis of autologous stem cell transplantation in refractory and relapsed Hodgkin lymphoma: Insights from a North African single-institution study.

172 Background: The standard therapy for primary refractory or relapsed Hodgkin lymphoma (HL) involves the administration of high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT). Nevertheless, several risk factors may influence survival outcomes. We assessed outcomes of patients in this setting who underwent HDC/ASCT by performing survival analysis and studying prognostic factors affecting survival. Methods: We conducted a single-institution retrospective analysis of patients with relapsed/refractory HL who received HDC/ASCT between January 2018 and December 2022. Patients’ status evaluation before ASCT was performed by Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) Scan and Computed Tomography (CT) Scan. The used conditioning regimen was BEAM (Carmustine, Etoposide, Cytarabine, and Melphalan). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, and survival differences between groups were assessed using the Log-Rank test. Results: Thirty-five patients diagnosed with relapsed/refractory HL were included in the study. Among them, 26 patients (74%) had refractory disease, while 9 patients (26%) relapsed following completion of first-line chemotherapy. All patients were treated with HDC/ASCT. Prior to ASCT, 30 patients underwent assessment using FDG-PET Scan, while CT Scan was employed for evaluation in 5 patients. Twenty-three patients (66%) were in complete remission, 8 patients (23%) were in partial remission, and 4 patients (11%) had progressive disease. With a median follow-up of 24.36 months after transplantation, 28 patients (80%) were in remission, 6 patients (17%) had disease progression, and one patients died of septic shock. The 2-year PFS and OS rates for the total population were 85.4% and 97.1%, respectively. Response to first-line chemotherapy did not have a substantial impact on prognosis, as evidenced by a 2-year PFS rate of 76.2% vs. 88.9% (p=0.88) and a 2-year OS rate of 100% vs. 96.2% (p=0.56) for patients with relapsed and refractory disease, respectively. The 2-year PFS and OS rates for patients receiving autograft during complete remission, partial response, and tumor progression were 93.8% vs. 87.5% vs. 50% (p=0.005), respectively; and 95.7% vs. 100% vs. 100%, respectively (p=0.77). Patients who had negative pre-transplant PET-Scans demonstrated a 2-year PFS rate of 92.9% vs. 64.8% for those with positive PET-scans (p=0.004). Conclusions: The findings of our study affirm the established practice of HDC/ASCT for individuals facing relapsed/refractory HL. The disease status at transplant and the pre-transplant PET-Scan status prove to be crucial factors in predicting patients’ outcomes, while response to first-line chemotherapy did not influence prognosis.

Feasibility of collecting longitudinal patient-reported outcomes in individuals with relapsed or refractory large B-cell lymphoma who received chimeric antigen receptor T-cell (CART) therapy

PurposeChimeric antigen receptor T-cell (CART) therapy has shown clinical efficacy in refractory and relapsed large B-cell lymphomas, but is associated with serious acute and long-term toxicities. To understand the patient perspective, we measured a patient-reported outcome (PRO), specifically, health-related quality of life (HRQoL), at multiple time points over one year.MethodsThis was a prospective feasibility study of a cohort of patients who were eligible for standard of care CART therapy, tisagenlecleucel. Demographic data and disease characteristics were collected. HRQoL was measured using FACT-Lym at baseline, and months 1, 3, 6 and 12. FACT-Lym includes FACT-G (physical, social, emotional and functional well-being domains), plus a lymphoma subscale.ResultsThirty-four of 35 patients approached, consented to participate. Two of them did not receive their infusion due to progressive disease. 50% were female and median age was 62 (23–77). Twenty-nine patients (91%) completed baseline FACT-Lym and 20 of 21 (95%) eligible patients completed 12-month FACT-Lym. 52% completed all 4 post-baseline FACT-Lym measures. Exploratory analyses for changes in FACT-Lym scores are reported.ConclusionIt is feasible to measure longitudinal PROs in patients who receive CART therapy. This study will inform future studies in evaluating the patient perspective on CART therapy.

Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy. We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events. Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2). In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.

Early Toxicity and Efficacy of Four Different Conditioning Regimens for Autologous Hematopoietic Cell Transplantation in Patients With Lymphoma: Impact of Drug Shortages in a Resource-Constrained Country

High-dose therapy followed by autologous hematopoietic cell transplant (AHCT) remains a viable consolidation strategy for a subset of patients with relapsed or refractory (R/R) lymphomas. BEAM (carmustine, etoposide, cytarabine, and melphalan) is widely recognized as the predominant conditioning regimen due to its satisfactory efficacy and tolerability. Nevertheless, shortages of carmustine and melphalan have compelled clinicians to explore alternative conditioning regimens. The aim of this study was to compare the toxicity and transplant outcomes following BEAM, CBV (carmustine, etoposide, cyclophosphamide), BuMel (busulfan, melphalan), and BendaEAM (bendamustine, etoposide, cytarabine, melphalan). We retrospectively analyzed data from 213 patients (CBV 65, BuMel 42, BEAM 68, BendaEAM 38) with R/R lymphomas undergoing AHCT between 2014 and 2020. Multivariate models were employed to evaluate toxicity and transplant outcomes based on conditioning type. Among grade III to IV toxicities, oral mucositis was more frequently observed with BuMel (45%) and BendaEAM (24%) compared to BEAM (15%) and CVB (6%, P ≤ .001). Diarrhea was more common with BendaEAM (42%) and less frequent with BuMel (7%, P = .01). Acute kidney injury was only found after BendaEAM (11%). Febrile neutropenia and infectious complications were more frequent following BendaEAM. Frequencies of other treatment-related toxicities did not significantly differ according to conditioning type. BendaEAM (odds ratio [OR] 3.07, P = .014) and BuMel (OR 4.27, P = .002) were independently associated with higher grade III to IV toxicity up to D+100. However, there were no significant differences in relapse/progression, nonrelapse mortality, progression-free survival, or overall survival among the four regimens. BuMel and BendaEAM were associated with a higher rate of grade III to IV toxicity. Carmustine-based regimens appeared to be less toxic and safer; however, there were no significant differences in transplant outcomes. The utilization of alternative preparative regimens due to drug shortages may potentially lead to increased toxicity after AHCT for lymphoma.

Analysis of 10 cases of brentuximab vedotin combined with chemotherapy in the treatment of children with refractory and or relapsed classic Hodgkin lymphoma

Objective: To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin's lymphoma (R/R cHL). Methods: Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment. Conclusion: Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin's lymphoma in children.

Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma

Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma after two or more lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help mitigate the risk of cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review. Among 128 patients evaluated, 95% completed cycle 1, and 85% completed four or more cycles. At 20.1months' efficacy follow-up, objective response rate was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events occurred in 16% of patients. The most common treatment-emergent adverse events were cytokine release syndrome [56%; grade ≥31.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%). Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.

Safety and activity of lenalidomide in combination with obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase 1/2 trial

Rituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma. In this single-arm, open-label, phase 1/2 trial, we enrolled patients with relapsed or refractory WHO Grade 1-3A follicular lymphoma, marginal zone lymphoma and small lymphocytic lymphoma and adequate performance status (ECOG 0-2) at the MD Anderson Cancer Center. We excluded patients with evidence of ongoing transformation to aggressive lymphoma. During phase 1, 1000mg intravenous obinutuzumab was administered with three predefined levels of oral lenalidomide in a 3+3 dose escalation design to establish lenalidomide 20mg as the recommended phase 2 dose. During phase 2, patients received induction therapy with six 28-day cycles of lenalidomide 20mg with intravenous obinutuzumab 1000mg. In accordance with our prior experience with lenalidomide plus rituximab, patients who were responding to the combination could receive up to 6 additional cycles (up to 12 cycles in total) of combination therapy. Dosing of obinutuzumab was continued in all responding patients after cycle 6 every 2 months for a total of 30 months from the start of therapy. The decision of number of cycles of combination therapy beyond 6 was at discretion of the investigator and was included to allow individualisation of therapy to maximise response while minimising exposure. The co-primary objectives were to evaluate the safety and overall response, defined as the proportion of patients who achieved a complete or partial response in relapsed and refractory indolent non-Hodgkin lymphoma at the end of induction therapy, according to Cheson and colleagues (2007 criteria). The secondary endpoints were complete response after induction therapy and time to event endpoints including time to progression, progression free survival, and overall survival. Analyses were intent to treat in the efficacy cohort and per-treated in the safety population in all patients who received at least one dose of either investigational agent. This trial is registered with ClinicalTrials.gov, NCT01995669. Between June 03, 2014, and 07 March 2019, we completed planned enrolment, and 66 patients started therapy including 9 patients in phase 1 and 57 patients in phase 2. All patients were evaluated for safety and the 60 patients treated at the recommended phase 2 dose of lenalidomide 20mg were evaluable for activity. Grade 3-4 haematological toxicities included neutropenia 21% (14/66) and thrombocytopenia 11% (7/66) with no cases of febrile neutropenia. Grade 3-4 non-haematological toxicities included lung infection 8% (5/66), fatigue 8% (5/66) and rash 6% (4/66). By Cheson 2007 criteria, 90% (54/60, 95% CI: 79-96) achieved an overall response at the end of induction meeting the prespecified activity endpoint. Complete responses were seen in 33% (20/60, 95% CI: 22-47) at the end of induction. Median progression free survival, time to progression and overall survival have not been reached after median follow-up of 41.7 months. Estimated 4-year progression free survival rates were 55% (95% CI: 42-73), time to progression of 56% (95% CI: 43-74) and overall survival of 84% (95% CI: 74-95). Our findings suggest that oral lenalidomide with obinutuzumab is safe and highly active in patients with relapsed and refractory indolent B cell non-Hodgkin lymphoma and is associated with prolonged remission duration. The study is limited by the lack of a control arm leading to cross-trial comparisons to evaluate activity. Future randomised trials comparing this regime to rituximab and lenalidomide are warranted. Genentech and an MD Anderson Core grant.

Phase IB Study of Oral Selinexor in Combination with Rituximab and Platinum Chemotherapy in Patients with Relapsed/Refractory B-Cell Lymphoma-Final Analysis.

Selinexor is an oral selective inhibitor of exportine-1 (XPO1) with efficacy as a single agent in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We conducted a study investigating the combination of selinexor with rituximab and platinum-based chemotherapy in B-cell lymphoma. We conducted a phase 1b, dose-escalation, and expansion trial, which enrolled patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Patients received oral selinexor according to a 3 + 3 design in combination with rituximab and dexamethasone, high-dose cytarabine, oxaliplatine (DHAOX) or gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy. A total of 39 patients were enrolled, 27 during the escalation phase and 12 during the expansion phase. Most patients had diffuse large B-cell lymphoma (DLBCL; 77%). Group R-DHAOX was prematurely closed to inclusion due to a recommendation from the French drug agency, independent of this trial. A recommended phase 2 dose (RP2D) of selinexor in association with R-GPD was established at 40 mg on days 1, 8, and 15 of each 21-day cycle. In a population of 18 patients treated at this dose of selinexor, the most frequent grade 3-4 adverse events were hematological. With this regimen, seven obtained a complete metabolic response and five a partial response. The median PFS was 5.8 months. Among the patients with R/R B-cell lymphoma, selinexor at a weekly dose of 40 mg with R-GDP is feasible for outpatients, with a generally acceptable safety profile.

Characteristics of relapsed and refractory paediatric Hodgkin lymphoma; a 10-year retrospective study of an LMIC.

With conventional standard treatment modalities, children and adolescents with Hodgkin lymphoma (HL) have long-term overall survival rates of over 90%. However, primary refractory disease may occur in 5%-10% of HL patients, while relapse occurs in 5%-10% of patients with early stage disease and up to 30% in an advanced stage. This retrospective study evaluated patient characteristics in cases of HL relapse and refractory and their response to second-line treatment of standalone chemotherapy or in combination with radiotherapy. A retrospective study was conducted by Indus Hospital and Health Network to determine the outcomes of paediatric patients with first and second relapses of HL between 2013 and 2022. A total of 742 patients were diagnosed with HL at Indus Hospital & Health Network. Of these, 48 (6.5%) patients presented with relapse and 35 (4.7%) with refractory disease after initial chemotherapy. In HL relapse patients, 57% were stage IV at initial diagnosis with the most common pathology being nodular sclerosis constituting 42.9% of patients. The most common age group was 6-10 years, 45.8%. B symptoms were experienced by 25 (52%) patients. A time to relapse of >12 months following diagnosis was seen in 69% and 3-12 months was seen in 31%.After receiving second-line treatment, complete remission was achieved by 34 (70.8%) patients, partial remission (PR) was seen in 5 (10.4%), disease progression in 5 (10.4%), 3 (6.3%) patients left during treatment and 1 (2.1%) had a treatment-related mortality. Re-radiation in second-line treatment was only required for 2 patients. The second relapse was seen in 11 (28.2%) of 39 complete and PR patients. Major limitations in the treatment of HL relapse in a low-resource setting are the non-availability of immunotherapy and autologous stem cell transplantation due to extreme financial burden and lack of capacity in facilities. Dedicated efforts are required to provide these facilities free of cost in low-middle income countries (LMICs).