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(Follicular Lymphoma)

Relevant Articles About FL (Follicular Lymphoma) Research and Clinical Trials

RELATED :DLBCL (Diffuse Large B Cell Lymphoma):MCL (Mantle Cell Lymphoma):MZL (Marginal Zone Lymphoma)

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FL (Follicular Lymphoma)Other CancersBiological: Epcoritamabgemcitabine and oxaliplatinLenalidomiderituximab and bendamustinerituximab and lenalidomiderituximab, cyclophosphamide, doxorubicin, vincristine, and prednisonerituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisonerituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatinrituximab, ifosfamide, carboplatin, and etoposide phosphateRecruitingAustraliaBelgiumCzechiaDenmarkFinlandFranceItalyNetherlandsNorwaySpainSwedenUnited KingdomUnited States 0NCT04663347Phase 1Phase 2EPCORE™ NHL-2
Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

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Manufacturing and Efficacy of Axi-Cel in R/R LBCL

KEY TAKEAWAYS

  • The ZUMA-1 & ZUMA-7 phase 1, 2 & 3 trials aimed to investigate the real-world axi-cel manufacturing experience and product characteristics in patients with R/R LBCL.
  • Researchers noticed that earlier axi-cel treatment in R/R LBCL enhances manufacturing success and product quality.

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is approved in many countries for patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL) within 12 months of first-line (1L) chemoimmunotherapy (based on the Phase 3 ZUMA-7 study [NCT03391466]) and in the third-line (3L) or later setting (3L+; based on the Phase 2 ZUMA-1 study [NCT02348216]).

A higher percentage of naive-like T cells was identified in axi-cel product manufactured in second line (2L; ZUMA-7) vs 3L+ (ZUMA-1) and was associated with improved therapeutic index without impacting the safety profile (Filosto S, et al. Blood Cancer Discov. 2024;5:21). With individualized therapies like axi-cel, timely and reliable delivery of product is essential (Tully S, et al. JCO Clin Cancer Inform. 2019;3:3). Thus, understanding axi-cel manufacturability for pts in 2L vs 3L+ is of interest, as well as examining the potential impact of line of therapy on product phenotype.

Jason Westin and the team aimed to assess the real-world axi-cel manufacturing experience and clinical trial product characteristics in patients with R/R LBCL treated in 2L versus 3L or later (3L+) settings.

Researchers performed an inclusive analysis involving patients with R/R LBCL enrolled in Kite Konnect® globally and undergoing leukapheresis for axi-cel treatment in either 2L or 3L and beyond (3L+) settings between April 19, 2022, and January 3, 2024. The first-pass manufacturing success rate (FP-MSR) was calculated as the percentage of initial patient lots meeting specification upon first attempt, relative to all first-attempt lots processed during the specified timeframe, excluding terminations for withdrawn patients.

Comparison of FP-MSR between 2L and 3L+ cohorts utilized a generalized linear model with a binary distribution and fixed effect test. Additionally, analysis of apheresis and axi-cel product cell phenotypes, specifically the proportion of naive-like T cells (CCR7+CD45RA+ within CD3+ cells), was conducted on patients from pivotal studies ZUMA-7 (2L) and ZUMA-1 (3L+), employing statistical assessment via Wilcoxon rank sum test.

About 4087 patients were included in the analysis, comprising 1342 patients treated in 2L and 2745 in 3L or later (3L+). The FP-MSR for patients in 2L was 96.42%, significantly higher than the 94.68% observed in 3L+ (P = 0.01). This difference translated to 17 more successfully manufactured lots per 1000 attempts in 2L compared to 3L+. Among evaluable patients in the full analysis set, the median percentage of naive-like T cells in apheresis was 4.11% (range: 0.09-56.60; n = 100) for 3L+ and 9.28% (range: 0.20-45.07; n = 126; P < 0.0001) for 2L.

Similarly, in the axi-cel product, the median percentage of naive-like T cells was 18.60% (range: 0.50-74.30; n = 101) for 3L+ and 35.10% (range: 0.06-74.90; n = 174; P < 0.0001) for 2L. Thus, patients in 2L exhibited approximately twice the median percentage of naive-like T cells compared to those in 3L+ in both apheresis and final product analyses.

The study concluded that axi-cel treatment in 2L significantly improves MSR by 1.74% compared to 3L or later (3L+), potentially enabling more patients to receive therapy on their 1 manufacturing attempt. Additionally, patients in 2L exhibited higher naive-like T cell frequencies in both apheresis and final product, highlighting potential advantages in treatment outcomes and product quality when axi-cel is administered earlier in the treatment sequence for R/R LBCL.

The trial was sponsored by the Kite, A Gilead Company.

Source: https://library.ehaweb.org/eha/2024/eha2024-congress/419512/jason.westin.real-world.manufacturing.experience.of.axicabtagene.ciloleucel.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Aot_id%3D29176%2Amarker%3D5101%2Afeatured%3D18527

Clinical Trials: https://clinicaltrials.gov/study/NCT03391466

https://clinicaltrials.gov/study/NCT02348216

Westin J, Rangel D, Ramírez J, et al. (2024). “REAL-WORLD MANUFACTURING EXPERIENCE OF AXICABTAGENECILOLEUCEL FOR PATIENTS WITH RELAPSED OR REFRACTORY LARGE B-CELLLYMPHOMA TREATED IN SECOND LINE VERSUS THIRD LINE OF THERAPY ANDBEYOND.” Presented at EHA 2024.

High ORR & Safety of Epcoritamab + Pola-R-CHP in 1L DLBCL

KEY TAKEAWAYS

  • The EPCORE NHL-5 phase 2 trial aimed to investigate the safety and antitumor activity of epcor + pola-R-CHP in patients with DLBCL.
  • The key endpoints were to determine DLTs, ORR/CR, TTR, and safety.
  • Researchers noted significant efficacy and safety of epcor + pola-R-CHP in newly diagnosed DLBCL; further investigation is ongoing.

Pola-R-CHP improved response rates and progression-free survival (PFS) vs cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line (1L) treatment (tx) for diffuse large B-cell lymphoma (DLBCL). However, there is still an unmet need to improve outcomes to achieve cure in 1L DLBCL.

Epcoritamab (epcor), a subcutaneous CD3xCD20 bispecific antibody, has demonstrated safety and efficacy in 1L DLBCL in combination with R-CHOP and is approved as monotherapy for relapsed or refractory (R/R) DLBCL after ≥2 lines of systemic therapy in the US, Europe, Japan, and other regions. Combining epcor with antineoplastic agents with varied MOAs may offer enhanced clinical benefit to patients. They reported safety and antitumor activity in patients with newly diagnosed DLBCL treated with epcor + pola-R-CHP.

David Lavie and the team aimed to assess the safety and antitumor activity of epcor combined with pola-R-CHP in newly diagnosed DLBCL, emphasizing its potential over standard tx’s.

Researchers performed an inclusive analysis of EPCORE NHL-5, an ongoing, multi-arm, open-label, global study. In arm 3, patients presented with newly diagnosed CD20+ DLBCL, including DLBCL not otherwise specified, high-grade B-cell lymphoma (HGBL) with MYC and BCL-2 and/or BCL-6 translocations (double/triple-hit), or follicular lymphoma (FL) grade 3B, with ECOG PS 0–2 and IPI score 2–5. Treatment consisted of 21-day cycles (C) with epcor + pola-R-CHP until C6, followed by 2 C of epcor monotherapy.

Epcor dosing involved step-up dosing in C1, followed by full doses (48 mg) weekly during C2–4 and every 3 weeks during C5–8. Additional management strategies included prednisone (n=17) or dexamethasone (n=20) for cytokine release syndrome (CRS) mitigation, and G-CSF or pegylated G-CSF post doxorubicin, cyclophosphamide, and pola during C1–6, with optional CNS prophylaxis. Key endpoints encompassed DLTs, investigator-assessed response (ORR/CR), time to response (TTR), and safety assessment.

They reported results from an analysis of EPCORE NHL-5 as of November 28, 2023. About 37 patients received epcor + pola-R-CHP: 51% were female, with a median age of 64 years. Diagnosis breakdown included 34 with DLBCL, 1 with HGBL, and 1 with FL grade 3B. No dose-limiting toxicities (DLTs) were observed.

Among 27 evaluable patients, the overall response rate (ORR) was 100%, with 89% achieving a complete response (CR) (n=24). Median follow-up was 5.8 months (95% CI: 4.8, 8.6). Median TTR and CR were 2.7 months (range: 1.3–3.3) and 2.8 months (range: 1.3–6.7), respectively. Treatment-emergent adverse events (TEAEs) are detailed, with 2 patients (5%) discontinuing epcor due to an AE and 3 patients (8%) discontinuing pola-R-CHP for the same reason. Common grade 3–4 TEAEs included neutropenia (65%), anemia (14%), and leukopenia (11%).

One patient experienced a fatal TEAE (septic shock), unrelated to epcor. CRS was predominantly low grade (32% G1, 16% G2), occurring most frequently after the first full epcor dose (C1, Day 15). CRS events were managed with prophylactic dexamethasone or prednisone, with resolutions typically within 2 days (range: 1–6). No immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. One patient had grade 4 hemophagocytic lymphohistiocytosis (HLH), which resolved with continued tx completion.

Biomarker analysis showed pharmacodynamic profiles consistent with epcor’s mechanism of action, with predictable cytokine elevations (IFN-gamma, IL-2, IL-6) after the initial full dose. Preliminary pharmacokinetic profiles and exposures of epcor were comparable to other tx combinations and monotherapy. Ongoing follow-up will provide additional data.

The study concluded with high ORR and CR rates across all patient subgroups for epcor + pola-R-CHP in newly diagnosed DLBCL, demonstrating a favorable safety profile compared to other tx’s. These findings support ongoing investigation of this combination, with forthcoming data including minimal residual disease (MRD) outcomes.

The trial was sponsored by the Genmab.

Source: https://library.ehaweb.org/eha/2024/eha2024-congress/422343/david.lavie.first.data.from.subcutaneous.epcoritamab2Bpolatuzumab.vedotin.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Aot_id%3D29171%2Amarker%3D5099%2Afeatured%3D18527

Clinical Trial: https://clinicaltrials.gov/study/NCT05283720

Lavie D, Avigdor A, Avivi I, et al. (2024). “FIRST DATA FROM SUBCUTANEOUS EPCORITAMAB+POLATUZUMAB VEDOTIN, RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, AND PREDNISONE (POLA-R-CHP) FOR FIRST-LINE DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): EPCORE NHL-5.” Presented at EHA 2024.

Glofit-GemOx Improves Survival in R/R DLBCL

KEY TAKEAWAYS

  • The STARGLO phase 3 trial aimed to investigate the efficacy and safety of Glofit-GemOx vs R-GemOx in ASCT-ineligible patients with R/R DLBCL.
  • The primary endpoint was to determine OS.
  • Researchers noticed that Glofit-GemOx significantly improves survival outcomes and maintains a tolerable safety profile.

Glofitamab is a CD20 bispecific antibody that is well tolerated with durable responses when given as fixed-duration monotherapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 prior lines of therapy (Dickinson, et al. NEJM 2022).

Jeremy Abramson and the team aimed to present efficacy and safety results of Glofit-GemOx versus rituximab (R)-GemOx in patients with R/R DLBCL.

They performed an inclusive analysis in which patients were randomized 2:1 to receive either Glofit-GemOx (8 cycles, plus 4 cycles glofitamab monotherapy) or R-GemOx (8 cycles) and were stratified by the number of prior therapies (1 vs ≥2) and refractoriness to the last treatment. Following obinutuzumab pretreatment, glofitamab was administered during Cycle 1 as weekly step-up doses (2.5/10 mg), then the 30 mg target dose every 21 days from Cycle 2 Day 1.

Patients enrolling after 1 prior therapy were considered ineligible for autologous stem cell transplant (ASCT) based on age ≥70 years, organ dysfunction, ECOG performance status ≥2, patient refusal for ASCT, or other investigator-assessed comorbidities. The primary endpoint was overall survival (OS). Secondary endpoints included independent review committee (IRC)-assessed progression-free survival (PFS), and complete remission (CR) rate. All patients provided informed consent. All study therapy constituted investigational or off-label use.

About 274 patients with DLBCL were enrolled (Glofit-GemOx, n=183; R-GemOx, n=91), including 172 (62.8%) after 1 prior therapy and 102 (37.2%) after ≥2 prior therapies. Overall, 153 (55.8%) had primary refractory disease and 166 (60.6%) were refractory to the last therapy. At primary analysis, there was a significant OS benefit with Glofit-GemOx versus R-GemOx (HR 0.59, 95% CI]: 0.40–0.89; P=0.011). With a median follow-up of 11.3 months, median OS was not reached (95% CI: 13.8–not evaluable) for Glofit-GemOx versus 9 months for R-GemOx (95% CI: 7.3–14.4).

Significant benefit of Glofit-GemOx was also observed in IRC-assessed PFS (HR 0.37, 95% CI: 0.25–0.55; P<0.0001) and CR rate (50.3 vs 22.0%; 95% CI: 16.3–40.3, P<0.0001). A follow-up analysis was conducted once all patients had completed therapy (cut-off date Feb 16, 2024; median follow-up of 20.7 months). Glofit-GemOx continued to demonstrate superior median OS (25.5 vs 12.9 months; HR 0.62, 95% CI: 0.43–0.88), median PFS (13.8 vs 3.6 months; HR 0.40, 95% CI: 0.28–0.57), and CR rate (58.5 vs 25.3%) versus R-GemOx, respectively. Median number of cycles received was higher with Glofit-GemOx versus R-GemOx (11 vs 4).

The adverse event (AE) rates were higher with Glofit-GemOx versus R-GemOx, including Grade (Gr) 3–4 AEs (69.4 vs 36.4%), Gr 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily CRS). Adjusting for exposure differences, AE rates were similar between arms. In patients exposed to glofitamab, CRS was the most frequently reported AE (Gr 1: 31.4%, Gr 2: 10.5%, and Gr 3: 2.3%), and events consistent with immune effector cell-associated neurotoxicity syndrome were reported in 4 patients (2.3%), all of which were concurrent with CRS.

The study concluded that Glofit-GemOx demonstrated statistically significant and clinically meaningful benefits in OS, PFS, and CR rate over R-GemOx in ASCT-ineligible patients with R/R DLBCL. Glofitamab is the first CD20 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomized Phase III trial. Glofit-GemOx, a fixed-duration, off-the-shelf regimen, was well tolerated with a safety profile consistent with the known risks of each individual agent.

The trial was sponsored by the Hoffmann-La Roche.

Source: https://library.ehaweb.org/eha/2024/eha2024-congress/4136516/jeremy.abramson.glofitamab.plus.gemcitabine.and.oxaliplatin.28glofit-gemox29.for.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Amarker%3D5097%2Afeatured%3D18498

Clinical Trial: https://clinicaltrials.gov/study/NCT04408638

Abramson J, Ku M, Hertzberg M, et al. (2024). “GLOFITAMAB PLUS GEMCITABINE AND OXALIPLATIN (GLOFIT-GEMOX)FOR RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA(DLBCL): RESULTS OF A GLOBAL RANDOMIZED PHASE III TRIAL (STARGLO).” Presented at EHA 2024.

Impact of HRQoL in Patients With CBCL

Impact of HRQoL in Patients With CBCL

KEY TAKEAWAYS

  • The study aimed to investigate the HRQoL in patients with primary CBCL, focusing on detailed analysis of subtype-specific impacts.
  • Researchers noted that patients with CBCL experience impaired HRQoL despite favorable prognosis.

Primary cutaneous B-cell lymphomas (CBCL) are a subset of rare malignant skin disorders, comprising 20%-30% of all primary cutaneous lymphomas (PCL). Unlike primary cutaneous T-cell lymphomas (CTCL), which have been extensively studied for their impact on health-related quality of life (HRQoL), CBCL-specific HRQoL research remains limited and lacks detailed analysis across its various subtypes.

A. E. C. Schirren and the team aimed to investigate the HRQoL in CBCL patients and identify independent factors contributing to its impairment.

They performed an inclusive analysis involving 100 patients with CBCL recruited from 8 German PCL centres between 2021 and 2022. Patients completed the dermatologic HRQoL questionnaire Skindex-29 and an investigator-designed ‘CBCL-Questionnaire’ that included additional inquiries on HRQoL and clinical characteristics.

The Skindex-29 assessment indicated mild to moderate impairment of HRQoL in these patients. In multiple regression analysis, worries about dying, feeling prejudiced/discriminated, and impairment of daily activities emerged as independently associated factors with HRQoL impairment. Patients with primary cutaneous follicle centre lymphoma on rituximab treatment and those with primary cutaneous marginal zone lymphoma (MZL) on watchful waiting exhibited the highest HRQoL impairment scores.

The study concluded that despite the typically indolent disease course and favorable prognosis of CBCL, patients experience impaired HRQoL. Factors such as worries about mortality, perceived discrimination, and treatment type were identified as significant contributors to this impairment. The findings underscore the importance of effective patient-doctor communication in assessing the holistic disease burden, especially as generic HRQoL tools may overlook disease-specific concerns.

No funding was received for this study.

Source: https://pubmed.ncbi.nlm.nih.gov/38279594/

Schirren AEC, Albrecht JD, Melchers S, et al. (2024). “Health-related quality of life and its influencing factors in patients with primary cutaneous B-cell lymphomas: A multicentric study in 100 patients.” J Eur Acad Dermatol Venereol. 2024 May;38(5):954-966. doi: 10.1111/jdv.19799. Epub 2024 Jan 26. PMID: 38279594.

Epcoritamab Shows Promise in RT: EPCORE CLL-1 Trial

KEY TAKEAWAYS

  • The EPCORE™ CLL-1 phase 1 & 2 trial aimed to investigate the efficacy and safety of epcoritamab in treating patients with RT.
  • Researchers observed promising efficacy and manageable safety of epcoritamab in RT.

RT is the transformation of chronic lymphocytic leukemia (CLL) into CD20+ diffuse large B-cell lymphoma (DLBCL), with poor prognosis exacerbated by prior CLL treatments and TP53 aberrations. Current chemoimmunotherapy (CIT) yields low complete response (CR) rates (≤20%). Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, is approved for relapsed or refractory large B-cell lymphoma. The ongoing EPCORE™ CLL​1 trial (NCT04623541) evaluates its safety and efficacy in RT. Preliminary results show promising efficacy and manageable safety.

Arnon P. Kater and the team aimed to assess the safety and efficacy of epcoritamab monotherapy in patients with Richter’s transformation (RT).

They performed an inclusive analysis of adults with biopsy-proven transformation to CD20+ DLBCL and a clinical history of CLL or small lymphocytic lymphoma. Patients with ≤2 prior lines of treatment for RT received epcoritamab 48 mg in 28-day cycles (QW, C1–3; Q2W, C4–9; Q4W, C≥10) until disease progression. To mitigate cytokine release syndrome (CRS), step-up dosing and corticosteroid prophylaxis were required in C1. Response was assessed using PET-CT per Lugano classification.

About 35 patients with RT had received epcoritamab as of October 5, 2023 (median follow-up of 8.1 months). A total of 91% of patients had ≥1 prior treatment line for CLL or RT, and 49% had prior treatment for RT. Most patients (57%) had received a Bruton’s tyrosine kinase or B-cell lymphoma 2 inhibitor prior to transformation, reflecting current treatment for CLL. The most common prior treatment for RT was an anti-CD20 monoclonal antibody-containing CIT regimen, primarily R-CHOP (in 76% of patients with prior treatment). As of data cutoff, 13 patients (37%) were still receiving epcoritamab.

In the response-evaluable population (n=26), the overall response rate (ORR) was 50%, and the complete response (CR) rate was 35%. Median times to response and CR were short (1.4 months and 2.4 months, respectively), and an estimated 53% of patients with CR remained in CR at 9 months (75% among patients with CR without prior treatment for RT). The most common nonhematologic treatment-emergent adverse event (TEAE) was cytokine release syndrome (CRS) (80%). Thrombocytopenia and anemia were observed in 40% of patients each at baseline and in 40% and 34% of patients, respectively, during the study per iwCLL criteria. CRS events primarily occurred following the first full dose, and most were low grade; only 1 patient (3%) had Grade 3 CRS.

Four patients had immune effector cell-associated neurotoxicity syndrome (ICANS) (Grade 1, n=2; Grade 2, n=2); all 4 patients had concurrent CRS. Clinical tumor lysis syndrome (CTLS) occurred in 3 patients (Grade 1–3, n=1 each). No CRS, ICANS, or CTLS events led to treatment discontinuation. Two patients discontinued treatment due to adverse events (AEs), and 3 patients had fatal TEAEs (general physical health deterioration [n=2] and sepsis). Data for all patients (N=42) from the fully enrolled cohort will be presented.

The study concluded that the first disclosure of data from a large RT cohort, now fully enrolled and with longer follow-up, demonstrates that epcoritamab treatment leads to encouraging ORR and CR rates in a high-risk population of patients with RT, with notably higher response rates in previously untreated RT. Safety was tolerable and consistent with prior reports; most CRS was low grade, and no new safety signals were observed.

Efforts to further mitigate CRS with C1 optimization, including an additional step-up dose of epcoritamab, are ongoing. These highly encouraging data support further evaluation of epcoritamab as a chemotherapy-free treatment option for patients with RT.

The trial was sponsored by the Genmab.

Source: https://library.ehaweb.org/eha/2024/eha2024-congress/422267/arnon.p.kater.single-agent.epcoritamab.leads.to.deep.responses.in.patients.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Aot_id%3D29194%2Amarker%3D5099%2Afeatured%3D18527

Clinical Trial: https://clinicaltrials.gov/study/NCT04623541

Kater A.P., Janssens A, Eradat H, et al. (2024). “SINGLE-AGENT EPCORITAMAB LEADS TO DEEP RESPONSES IN PATIENTS(PTS) WITH RICHTER’S TRANSFORMATION (RT): PRIMARY RESULTS FROMTHE EPCORE CLL-1 TRIAL.” Presented at EHA 2024.

Elderly MCL: Acala Boosts PFS in ECHO Trial

KEY TAKEAWAYS

  • The ECHO phase 3 trial aimed to assess the combination of acala with BR in elderly patients with untreated MCL in ECHO.
  • The primary endpoint was PFS.
  • The addition of acala to BR in ECHO trial for elderly patients with MCL significantly improved PFS and showed positive OS trends.

Aggressive initial treatments for mantle cell lymphoma (MCL) offer lasting responses and extended progression-free survival (PFS), but pose challenges for elderly or medically unfit individuals due to their poor tolerability. Combining the Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy (CIT; bendamustine + rituximab [BR]) as a first-line treatment for MCL (SHINE) has shown promise in prolonging PFS.

However, this approach has been associated with compromised overall survival (OS) because of increased toxicity.

Michael Wang and the team conducted a study that aimed to assess the efficacy of combining acalabrutinib with BR in elderly patients with previously untreated MCL in the randomized, double-blind, placebo-controlled Phase 3 ECHO trial.

Patients aged 65 years or older with previously untreated MCL and an ECOG performance status of 2 or less were randomly assigned in a 1:1 ratio to receive either ABR or placebo in combination with BR (PBR).

Enrollment took place between April 2017 and March 2023 across 195 global sites. BR treatment consisted of 6 cycles, followed by rituximab maintenance for 2 years in patients achieving a partial or complete response. Acala (100 mg twice daily) or placebo was administered until disease progression or unacceptable toxicity, with the option to switch to acala upon disease progression. The primary endpoint was PFS as assessed by an independent review committee.

About 598 patients were included in the analysis, evenly distributed with 299 patients in each arm. The median age was 71 years, and 76% had low/intermediate simplified MIPI while 13% had blastoid/pleiomorphic histology. Patient characteristics were well balanced between the two treatment arms. After a median follow-up of 45 months, 31.8% and 25.8% of patients continued treatment in the ABR and PBR arms, respectively.

Overall response rates (ORR) were 91.0% and 88.0% with ABR and PBR, respectively, with corresponding complete response rates of 66.6% and 53.5%. Median PFS was 66.4 months with ABR compared to 49.6 months with PBR (HR 0.73; 95% CI 0.57, 0.94; P=0.0160). OS data showed a positive trend favoring the ABR arm (HR 0.86; 95% CI 0.65, 1.13; P=0.27), despite 51 patients crossing over to acala after disease progression with PBR. COVID-19 deaths significantly influenced study outcomes.

After censoring for COVID-19 deaths, median PFS improved in both arms: not reached with ABR vs 61.6 months with PBR (HR 0.65; 95% CI 0.49, 0.86; P=0.0027). A similar trend was observed in OS (HR 0.78; 95% CI 0.56, 1.07; P=0.12).

Regarding safety, grade ≥3 adverse events (AEs) and serious AEs were comparable between both arms. Among grade ≥3 AEs of clinical interest, atrial fibrillation, hypertension, neutropenia, infections, and pneumonia were reported in both arms. COVID-19-related events and deaths were also reported, with discontinuation of acala due to AEs occurring in a higher proportion of patients compared to the placebo arm, primarily due to COVID-19.

The study concluded that adding acalabrutinib to BR in the ECHO trial for elderly patients with untreated MCL resulted in a statistically significant enhancement in PFS over a 45-month median follow-up period. Additionally, a favorable trend in OS was observed, particularly evident in patients unaffected by COVID-19.

The trial was sponsored by the Acerta Pharma BV.

Source: https://library.ehaweb.org/eha/2024/eha2024-congress/4136515/michael.wang.acalabrutinib.plus.bendamustine.and.rituximab.in.untreated.mantle.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Amarker%3D5097%2Afeatured%3D18498

Clinical Trial: https://clinicaltrials.gov/study/NCT02972840

Wang M, Mayer J, Belada D, Song Y, et al. (2024). “CALABRUTINIB PLUS BENDAMUSTINE AND RITUXIMAB IN UNTREATEDMANTLE CELL LYMPHOMA: RESULTS FROM THE PHASE 3, DOUBLE-BLIND,PLACEBO-CONTROLLED ECHO TRIAL.” Presented at EHA 2024. (LB3439)

Advancing Therapeutic Solutions for MCL: Bridging the Gap

KEY TAKEAWAYS

  • The study aimed to investigate real-world outcomes of post-cBTKi treatment in patients with r/r MCL for comprehensive understanding.
  • The results revealed the critical importance of ongoing development of novel therapeutics to address unmet patient needs.

Covalent Bruton’s tyrosine kinase inhibitors (cBTKis) are standard treatment for relapsed/refractory mantle cell lymphoma (r/r MCL), but limited response duration and resistance are observed.

Patrick Squires and the team aimed to assess post-cBTKi clinical and economic outcomes in patients with r/r MCL, addressing existing evidence gaps.

Researchers utilized 2010-2019 U.S. Medicare claims to identify elderly patients (aged ≥66 years) newly diagnosed with MCL. These patients received third-line (3L) treatment and previously demonstrated evidence of cBTKi use. Outcomes evaluated ≥12 months post third-line treatment initiation included treatment patterns, healthcare resource utilization, costs, and overall survival related to both all-cause and mantle cell lymphoma-specific factors.

About 230 elderly patients with r/r MCL who underwent 3L treatment revealed that all had previously been exposed to cBTKis in earlier therapy regimens. Their mean age was 75.0, with 21.7% aged over 80 years, and the majority were male (67.4%) and White (93.9%).

Among the common 3L treatments administered, chemotherapy (26.1%), lenalidomide (18.7%), and bortezomib (18.3%) were prominent. A quarter of patients (25.7%) received a cBTKi, predominantly ibrutinib (17.8%) and acalabrutinib (7.8%).

The overall survival post-3L treatment initiation was notably low, with a median of 9.4 months and a 1-year survival rate of 43.7%. Patients exhibited elevated healthcare resource utilization, with 73.6% experiencing hospitalization, and incurred substantial costs, averaging $145,726 within the 12 months following 3L initiation.

The study concluded that within this patient subpopulation, a significant unmet need persists, underscoring the critical importance of continued advancement in the development of novel therapeutics.

This study was supported by Bristol Myers Squibb.

Source: https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)00226-X/abstract#articleInformation

Squires P, Puckett J, Ryland KE, et al. (2024). “Real-world Treatment Patterns, Survival, and Economic Burden among Elderly MCL Patients Previously Treated with cBTKis.” DOI: https://doi.org/10.1016/j.clml.2024.05.023

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