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DLBCL

(Diffuse Large B Cell Lymphoma)

Relevant Articles About DLBCL (Diffuse Large B Cell Lymphoma)
Lymphoma Research and Clinical Trials

RELATED :FL (Follicular Lymphoma):MCL (Mantle Cell Lymphoma):MZL (Marginal Zone Lymphoma)

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OncWeekly Featured Trials

DLBCL (Diffuse Large B Cell Lymphoma)Other CancersR-mini-CHOPR-pola-mini-CHPRecruitingAustraliaDenmarkFinlandItalyNew ZealandNorwaySweden 0NCT04332822Phase 3POLAR BEAR
A Randomized, Multicenter, Phase III Trial Comparing Treatment With R-mini-CHOP With R-mini-CHP + Polatuzumab Vedotin in Patients With Diffuse Large Cell B Cell Lymphoma

A Randomized, Multicenter, Phase III Trial Comparing Treatment With R-mini-CHOP With R-mini-CHP + Polatuzumab Vedotin in Patients With Diffuse Large Cell B Cell Lymphoma

DLBCL (Diffuse Large B Cell Lymphoma)FL (Follicular Lymphoma)MCL (Mantle Cell Lymphoma)Other CancersBiological: EpcoritamabActiveNot RecruitingAustraliaCanadaDenmarkFinlandFranceGermanyItalyKorea, Republic ofNetherlandsPolandSingaporeSpainSwedenUnited KingdomUnited States 0NCT03625037Phase 1Phase 2EPCORE™ NHL-1
First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma

First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma

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Lymphoma

ac4C RNA Modification and Epigenetic Therapies in DLBCL

KEY TAKEAWAYS The study aimed to investigate NAT10's role and mechanisms in DLBCL using clinical samples and various assays. The results showed the essential role of ac4C RNA modification mediated by NAT10 in DLBCL and provided insights into novel epigenetic-based...

Jul 5, 2024

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Loncastuximab & Rituximab Combo: Effective in Rel/Ref FL

KEY TAKEAWAYS

  • The phase 2 trial aimed to evaluate loncastuximab tesirine in rel/ref FL to establish treatment efficacy.
  • The primary endpoint was CR.
  • The results showed that the combination of loncastuximab and rituximab was well tolerated and highly effective, achieving metabolic CR.

In the absence of an established standard of care (SOC) for relapsed/refractory follicular lymphoma (rel/ref FL), loncastuximab tesirine stands out with its unique targeting of CD19, offering a potential novel treatment approach.

Claudia Marcela Grandas Moreno and the team aimed to assess the efficacy of loncastuximab tesirine in patients with rel/ref FL.

Adult patients with rel/ref FL, previously treated with at least one line of systemic therapy and meeting GELF criteria or experiencing disease progression within 24 months (POD24) at enrollment, were eligible. The primary study endpoint was complete response (CR) by week 12 PET/CT.

Treatment involved 4 weekly doses of intravenous rituximab at 375mg/m2, followed by 1 dose every 8 weeks for a total of 5 doses, alongside intravenous loncastuximab at 0.15mg/kg every 3 weeks for 2 doses, then 0.075mg/kg every 3 weeks for a total of 7 doses. Premedication with dexamethasone 4 mg twice daily for 3 days was mandatory. Patients achieving CR at week 21 ceased loncastuximab and received 2 doses of rituximab every 8 weeks.

The results revealed that 26 patients were enrolled from January 2022 to July 2023, with 25 evaluable for toxicity and 21 for response. The median age was 68 years (range: 47 to 89), with a majority being women (n=14; 54%) and presenting with advanced-stage disease (n=20; 77%) and high-risk FLIPI score (n=13; 50%). About 12 patients (46%) experienced disease progression within 24 months after immunochemotherapy, with a median of one prior therapy line (range: 1 to 6).

Common adverse events included elevation in alkaline phosphatase, ALT, AST, maculo-papular rash, fatigue, thrombocytopenia, photosensitivity, leg edema, anasarca, and neutropenia. All toxicities were resolved with supportive management and dose delays (n=4).

Among the initial 10 patients meeting pre-specified criteria to proceed to stage II, CR was observed in 7. Of 21 patients evaluated for response, the overall response rate at week 12 was 95.2%, with a CR rate of 66.7% (n=14) and a partial response (PR) rate of 28.6% (n=6). All CR were sustained, and 4 of 6 PRs improved to CR by week 21, resulting in a best CR rate of 86% (n=18). All 7 patients who completed the study remained in CR after the end of treatment, with a median follow-up of 4.8 months (range: 3.2 to 6.7).

The study concluded that combining loncastuximab with rituximab demonstrated high effectiveness and favorable tolerability, achieving a metabolic complete response rate.

The trial was sponsored by Juan P. Alderuccio, MD, from the University of Miami.

Source: https://ons.confex.com/ons/2024/meetingapp.cgi/Paper/14994

Clinical Trial: https://clinicaltrials.gov/study/NCT04998669

Grandas Moreno CM, Rodriguez A, Medina Andara LV, et al. (2024). “Safety and Efficacy of Loncastuximab Tesirine with Rituximab in Follicular Lymphoma.” Presented at ONS 2024 (RS24)

IRTA1 Positivity in PCMZL: Implications Beyond IgM Expression

KEY TAKEAWAYS

  • The study aimed to investigate IRTA1 and MNDA expression in PCMZLs to understand their role in distinguishing IgM+ and class-switched subsets and potential implications for patients with both subtypes.
  • Researchers concluded that while IRTA1 identifies MALT-lymphoma-like PCMZLs predominantly IgM+, it suggests that distinguishing between PCMZL subsets should not rely solely on heavy chain expression.

It has been proposed that primary cutaneous marginal zone lymphomas (PCMZLs) comprise a MALT-lymphoma-like IgM+ subset and a class-switched subset, deviating from most other MALT lymphomas. Whether MALT lymphoma-associated biomarkers IRTA1 and MNDA support this distinction and elucidate the co-occurrence of both subsets remains uncertain.

Eric D. Carlsen and the team aimed to assess the expression of MALT lymphoma-associated biomarkers IRTA1 and MNDA in PCMZLs.

They performed an inclusive analysis involving 25 PCMZLs from 21 patients. They conducted staining for IRTA1 using in situ hybridization and for MNDA via immunohistochemistry. Additionally, polymerase chain reaction (PCR)-based B-cell clonality studies were conducted on biopsy specimens of metachronous lesions in 2 patients, showing different heavy chains. All findings were subsequently correlated with histopathologic and clinical data.

About 5 out of 6 IgM+ PCMZLs were found to be IRTA1+, compared to three out of 18 evaluable class-switched cases (P = 0.0069). Notably, two class-switched cases positive for IRTA1 were identified in patients with clonally-related IRTA1+ IgM+ PCMZLs.

Furthermore, IRTA1 positivity exhibited a statistically significant correlation with several MALT-lymphoma-associated histopathologic findings. Conversely, all PCMZL cases exhibited some degree of MNDA expression, with no discernible differences between IgM+ and class-switched cases.

The study concluded that IRTA1 is a marker for identifying MALT-lymphoma-like PCMZLs, primarily observed in IgM+ cases but not exclusively. This finding supports the existence of two distinct subsets within PCMZLs. However, it suggests that distinguishing between these subsets should not rely solely on heavy chain expression.

Source: https://pubmed.ncbi.nlm.nih.gov/34309899/

Carlsen ED, Bhavsar S, Cook JR, et al. (2024). “IRTA1 positivity helps identify a MALT-lymphoma-like subset of primary cutaneous marginal zone lymphomas, largely but not exclusively defined by IgM expression.” J Cutan Pathol. 2022 Jan;49(1):55-60. doi: 10.1111/cup.14111. Epub 2021 Aug 8. PMID: 34309899.

Genetic Landscape of Transformed MZLs

KEY TAKEAWAYS

  • The study aimed to investigate the molecular mechanisms underlying HT in MZLs to improve understanding and treatment strategies.
  • Researchers noticed that distinct clinicopathologic and genetic features of HT-MZLs suggest a unique entity, potentially differentiated from MZL and de novo non-GCB type DLBCL, with TBL1XR1 mutations as a predictive marker.

Marginal zone lymphomas (MZLs) are a heterogeneous group of slow-growing lymphoproliferative disorders. However, a subset of patients experiences histologic transformation (HT), leading to rapid progression to aggressive lymphoma.

Anqi Li and the team aimed to investigate the role of TBL1XR1 mutations as a potential predictor of HT in MZL.

Researchers performed an inclusive analysis involving 43 MZLs with histologic transformation (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without MYC, BCL2, and BCL6 rearrangements. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs underwent 148-gene targeted exome sequencing. The study compared clinicopathologic features and genetic alterations in patients with HT-MZL, MZLs, and DLBCLs.

About the study’s results, all 43 HT-MZL cases corresponded to DLBCLs, with none harboring BCL2 and MYC and/or BCL6 rearrangements. HT-MZLs exhibited higher rates of bone marrow involvement and elevated lactate dehydrogenase levels compared to MZLs. Upregulated expression of BCL6, MUM1, C-MYC, and Ki-67 was more common in HT-MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%).

Patients with TBL1XR1 mutations showed a trend toward worse progression-free survival. Additionally, HT-MZLs displayed significantly higher frequencies of TBL1XR1 and ID3 mutations compared to MZLs and non-germinal center B-cell (GCB) type DLBCLs. PIM1 mutations, which were frequently observed in DLBCLs, showed a significant association with TBL1XR1 mutations but were less common in HT-MZLs with TBL1XR1 mutations.

The study concluded that the clinicopathologic and genetic characteristics of HT-MZLs suggest their potential differentiation from both MZL and de novo non-germinal center B-cell (GCB) type DLBCL. Notably, TBL1XR1 mutations emerged as potential predictors of histologic transformation in MZL.

The study was sponsored by the National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality.

Source: https://pubmed.ncbi.nlm.nih.gov/37941429/

Li A, Yi H, Deng S, et al. (2024). “The genetic landscape of histologically transformed marginal zone lymphomas.” Cancer. 2024 Apr 15;130(8):1246-1256. doi: 10.1002/cncr.35072. Epub 2023 Nov 8. PMID: 37941429.

Efficacy of Mosunetuzumab in Treating R/R B-cell NHL

Efficacy of Mosunetuzumab in Treating R/R B-cell NHL

KEY TAKEAWAYS

  • The phase 1 & 2 trial aimed to investigate the efficacy and safety of Mosunetuzumab in treating patients with R/R follicular lymphoma after ≥ 2 prior therapies.
  • Researchers noticed favorable safety profiles and outpatient suitability of Mosunetuzumab monotherapy for R/R B-cell NHL, including FL.

Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody approved in Europe and the United States for relapsed/refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior therapies.

Matthew Matasar and the team aimed to investigate the efficacy and safety of Mosunetuzumab monotherapy as a treatment for R/R B-cell NHL, including FL.

They performed an inclusive analysis of interim safety data from the mosunetuzumab GO29781 phase I/II dose-escalation study in R/R NHL, specifically focusing on FL.

About 218 patients with R/R NHL, including 90 with R/R FL, underwent a median of eight 21-day cycles of intravenous mosunetuzumab with step-up dosing in Cycle 1 (Day 1: 1 mg; Day 8: 2 mg; Day 15/Day 1 of Cycle 2: 60 mg; Day 1 of Cycle 3 and onwards: 30 mg). Cytokine release syndrome (CRS) was the most frequent adverse event (AE), observed in 39.4% (NHL) and 44.4% (FL) of patients, mostly occurring during Cycle 1 at the first loading dose; the majority were grade 1/2. CRS events were managed with supportive care, steroids, and tocilizumab based on protocol guidelines.

Immune effector cell-associated neurotoxicity syndrome was rare, reported in 0.9% (NHL) and 1.1% (FL) of patients. Neutropenia occurred in 27.5% (NHL) and 28.9% (FL) of patients (mostly grade 3/4) and was effectively managed using granulocyte colony-stimulating factor. Tumor lysis syndrome occurred in 0.9% (NHL) and 1.1% (FL) of patients (all grade 3/4 with CRS; all resolved).

The study concluded that Mosunetuzumab monotherapy demonstrates promising results as a treatment option for R/R B-cell NHL, including FL, with low rates of severe AE’s, notably CRS. Moreover, its suitability for outpatient administration in community settings suggests a convenient therapeutic approach. The inclusion of adapted protocol guidance for managing select AEs further enhances the safety profile of Mosunetuzumab treatment.

The study was sponsored by the Genentech, Inc.

Source: https://pubmed.ncbi.nlm.nih.gov/38195322/

Clinical Trial: https://clinicaltrials.gov/study/NCT02500407

Matasar M, Bartlett NL, Shadman M, et al. (2024). “Mosunetuzumab Safety Profile in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma: Clinical Management Experience From a Pivotal Phase I/II Trial.” Clin Lymphoma Myeloma Leuk. 2024 Apr;24(4):240-253. doi: 10.1016/j.clml.2023.12.005. Epub 2023 Dec 12. PMID: 38195322.

MTV as a Prognostic Indicator in Advanced Follicular Lymphoma

KEY TAKEAWAYS

  • The RELEVANCE phase 3 trial aimed to investigate the prognostic value of baseline PET parameters in treatment-naïve FL patients.
  • Researchers concluded that baseline TMTV serves as an independent predictor of PFS in advanced FL patients.

We investigated the prognostic value of baseline positron emission tomography (PET) parameters in treatment-naïve follicular lymphoma (FL) patients in the phase III RELEVANCE trial. A. S. Cottereau and his team aimed to compare the outcomes between the immunomodulatory combination of lenalidomide and rituximab (R2) and R-chemotherapy (R-chemo), followed by R maintenance therapy.

Researchers performed an inclusive analysis of baseline characteristics in the entire PET-evaluable population (n = 406/1032), ensuring a well-balanced distribution between treatment arms. The methodology involved extracting the maximal standard uptake value (SUVmax) and the standardized maximal distance between 2 lesions (SDmax), with the total metabolic tumor volume (TMTV) calculated using the 41% SUVmax method.

With a median follow-up of 6.5 years, the 6-year progression-free survival (PFS) for the entire PET-evaluable population (n = 406/1032) in the phase III RELEVANCE trial was 57.8%. The median TMTV was 284 cm3, SUVmax was 11.3, and SDmax  was 0.32 m-1, demonstrating no significant difference between treatment arms. High TMTV (>510 cm3) and FLIPI were associated with an inferior PFS (P = 0.013 and P = 0.006, respectively), while SUVmax and SDmax showed no significant association (P = 0.08 and P = 0.12, respectively). In multivariable analysis, follicular lymphoma international prognostic index (FLIPI ) and TMTV remained significantly associated with PFS (P = 0.0119 and P = 0.0379, respectively). Combining these adverse factors stratified the population into 3 risk groups: no risk factors (40%), 1 factor (44%), or both (16%), with 6-year PFS rates of 67.7%, 54.5%, and 41.0%, respectively. No significant interaction was observed between treatment arms and TMTV or FLIPI (P = 0.31 or P = 0.59, respectively). The high-risk group (high TMTV and FLIPI 3-5) had similar PFS in both arms (P = 0.45) with a median PFS of 68.4% in the R-chemo arm versus 71.4% in the R2 arm.

The study concluded that baseline TMTV is an independent predictor of PFS in patients with advanced FL, even in antibody maintenance.

Source: https://pubmed.ncbi.nlm.nih.gov/37898239/

Cottereau AS, Rebaud L, Trotman J, et.al (2024). Metabolic tumor volume predicts outcome in patients with advanced stage follicular lymphoma from the RELEVANCE trial. Ann Oncol. 2024 Jan;35(1):130-137. doi: 10.1016/j.annonc.2023.10.121. Epub 2023 Oct 28. PMID: 37898239.

 

EORTC-Derived Symptom Measures for Lymphoma: A Mixed-Method

KEY TAKEAWAYS

  • The study aimed to investigate the patient-reported symptoms of CLL/SLL and MCL and assess their impact on patients through conceptually-selected EORTC Item Library items.
  • Researchers noticed a significant potential in utilizing the EORTC Item Library to assess CLL/SLL- and MCL-related symptoms, with promising implications for clinical trial settings.

No dedicated measures exist for assessing patient-reported symptoms in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or mantle cell lymphoma (MCL). Jessica T Markowitz and her team aimed to uncover and understand CLL/SLL- and MCL-related symptoms, exploring their impact on patients’ lives. Through a qualitative and quantitative assessment of conceptually-selected EORTC Item Library items, the study seeks to identify promising measures for these rare blood and lymphatic cancers.

Researchers performed an inclusive analysis, commencing with a comprehensive literature review, clinician consultations, and patient interviews to identify and code concepts vital to patients. Cognitive debriefing of the selected library items was undertaken with patients. The study organized CLL/SLL and MCL-related symptoms and impacts into a structured conceptual model, subsequently mapped to item sets from the EORTC Item Library. The quantitative component involved exploratory macro-level Rasch measurement theory (RMT) analysis, offering supportive quantitative insights on the identified item sets.

About 41 participants (21-MCL; 20-CLL/SLL), along with 5 clinicians, engaged in the qualitative study. Subsequently, 57 unique patients (30-MCL; 27-CLL/SLL) completed the EORTC items. The conceptual models derived from the qualitative analysis delineated symptoms and functional impacts of CLL/SLL and MCL. Symptom domains encompassed swollen lymph nodes, B symptoms, abdominal issues, pain, fatigue, subjective cognitive impairment, anemia-related symptoms, bleeding, infection, and miscellaneous issues (appetite loss, temperature fluctuation, rash, weight gain, sleep problems, cough). Impact domains included physical function, role function, and other functions (psychological, social). Cognitive debriefing demonstrated that separate item sets for CLL/SLL and MCL-related symptoms were well understood and aligned with patients’ experiences. All selected items were encompassed in the conceptual models. In the exploratory RMT analysis, the item sets demonstrated sufficient coverage of the continuum of CLL/SLL- and MCL-related symptom severity.

The study concluded that the EORTC Item Library demonstrates qualitative and early quantitative evidence supporting its use in assessing CLL/SLL- and MCL-related symptoms and impacts. These items are promising candidates for measurement of patient-reported disease symptoms in these populations. However, a larger sample size will be essential to establish the necessary psychometric properties for clinical trial use. Patients suffering from rare blood, bone marrow, and lymph node cancers experience chronic and debilitating symptoms, yet dedicated instruments for assessing their experiences are currently lacking. The researchers selected relevant and clinically meaningful symptoms from the EORTC Item Library that assess fatigue, B symptoms, and CLL/SLL- and MCL-specific symptoms. Through patient and clinician interviews, along with quantitative analyses, the study revealed no major concerns with using these item sets to assess CLL/SLL and MCL symptoms. Interviews with patients indicated a clear understanding and alignment with their experiences. All selected items were included in the conceptual models, suggesting their potential use in assessing patient-reported symptom endpoints in clinical trial settings for these diseases.

The study is sponsored by Eli Lilly & Company

Source: https://pubmed.ncbi.nlm.nih.gov/38252198/

Markowitz JT, Mazerolle F, Lovell T, et.al (2024). Mixed-methods research to support the use of new lymphoma-specific patient-reported symptom measures derived from the EORTC item library. J Patient Rep Outcomes. 2024 Jan 22;8(1):8. doi: 10.1186/s41687-024-00683-2. PMID: 38252198; PMCID: PMC10803695.

Pirtobrutinib Shows Promising Relief in Resistant MCL

KEY TAKEAWAYS

  • The study aimed to investigate the comprehensive profile of pirtobrutinib, assessing pharmacokinetics, pharmacodynamics, safety, and efficacy in r/r MCL patients.
  • Researchers noticed the promising safety and efficacy of pirtobrutinib, highlighting its potential as a valuable therapeutic option for r/r MCL patients.

Dominique D Davis and her team aimed to address the imperative need for effective treatments in relapsed/refractory mantle cell lymphoma (r/r MCL); this comprehensive review delves into the pharmacokinetics, pharmacodynamics, safety, and efficacy of pirtobrutinib, a recently FDA-approved Bruton’s tyrosine kinase inhibitor (BTKi).

Researchers performed an inclusive analysis to evaluate the accelerated approval of pirtobrutinib, a non-covalent Bruton’s tyrosine kinase inhibitor (BTKi), for the treatment of r/r MCL. The approval, granted on January 2023, was based on results from the open-label, multi-center phase 1/2 BRUIN trial.

In phase 1, 61 patients with r/r MCL received pirtobrutinib at 7 dose levels ranging from (25 to 300 mg). Notably, no maximum tolerated dose or dose-limiting toxicities were reported during this phase. Subsequently, in phase 2, 56 evaluable efficacy patients were administered a daily dose of 200 mg pirtobrutinib. The overall response rate (ORR) was 52% (95% CI 38-65), and for patients with a history of prior covalent BTKi, the ORR remained at 52% (95% CI 38-66). The most frequently reported adverse reaction of grade 3 or higher was neutropenia.

The study concluded with compelling evidence affirming the safety and efficacy of pirtobrutinib in extensively treated adults with r/r MCL. Notably, the drug’s utilization in cases resistant to current BTK inhibitors, coupled with favorable tolerability and response rates, underscores its promising therapeutic potential. Ongoing clinical trials investigating pirtobrutinib across various B-cell malignancies further emphasize its role as a versatile and valuable treatment option in the evolving landscape of targeted therapies.

Source: https://pubmed.ncbi.nlm.nih.gov/38043933/

Davis DD, Ohana Z, Pham HM, et.al (2024). Pirtobrutinib: A novel non-covalent BTK inhibitor for the treatment of adults with relapsed/refractory mantle cell lymphoma. J Oncol Pharm Pract. 2024 Jan;30(1):182-188. doi: 10.1177/10781552231216886. Epub 2023 Dec 3. PMID: 38043933.

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