Subscribe

Advertisement

MCL

(Mantle Cell Lymphoma)

Relevant Articles About MCL (Mantle Cell Lymphoma)
Research and Clinical Trials

RELATED :DLBCL (Diffuse Large B Cell Lymphoma):FL (Follicular Lymphoma):MZL (Marginal Zone Lymphoma)

Stories to Watch

VIEW ALL

VIEW ALL

Advertisement

OncWeekly Featured Trials

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

CLL (Chronic Lymphocytic Leukemia)FL (Follicular Lymphoma)MCL (Mantle Cell Lymphoma)Other CancersIbrutinibEnrolling by invitationArgentinaAustraliaBelgiumBrazilCanadaChinaColombiaCzechiaFranceGermanyGreeceHungaryIrelandIsraelItalyJapanKorea, Republic ofMexicoNetherlandsPolandPortugalPuerto RicoRussian FederationSpainSwedenTaiwanTurkeyUkraineUnited KingdomUnited States 9NCT01804686Phase 3CAN3001
A Long-term Extension Study of PCI-32765 (Ibrutinib)

A Long-term Extension Study of PCI-32765 (Ibrutinib)

Advertisement

Advertisement

LATEST

View More

Advertisement

Sign up for our emails

Trusted insights straight to your inbox and get the latest updates from OncWeekly

Privacy Policy

Latest Conferences

VIEW MORE

Brain View in 3D
Brain Cancer

Effective PT in Largest IM Patient Series

KEY TAKEAWAYS The study aimed to report outcomes from a substantial series of IM treated with curative-intent proton therapy. The study's findings concluded proton therapy effectively treated IM with acceptable toxicity, representing a substantial patient cohort....

Jun 28, 2024

Latest Conferences

VIEW ALL

VIEW ALL

RELATED CONTENT

VIEW ALL

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.

Axi-Cel: Cost-Effective Choice Over Mosun in Treatment Analysis

KEY TAKEAWAYS

  • The study aimed to evaluate axi-cel’s cost-effectiveness vs. mosun in 3L+ r/r FL patients from a US payer perspective.
  • The study concluded that axi-cel proves cost-effective over mosun, aligning with the $150k/QALY US threshold.

Recently, the US Food and Drug Administration has approved novel therapies for 3L+ relapsed/refractory follicular lymphoma (FL). These include anti-CD19 CAR-T therapies like axicabtagene ciloleucel (axi-cel) and CD20 × CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun).

Olalekan O Oluwole and the team aimed to evaluate the cost-effectiveness of axi-cel vs. mosun in 3Lpatients with r/r FL from a US payer standpoint.

The study utilized a three-state partitioned-survival model compared two treatments over a lifetime horizon in a hypothetical cohort of US adults (age ≥18) receiving 3L+ treatment for r/r FL. Trial data from ZUMA-5 and GO29781 informed progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via HRs applied to axi-cel survival curves.

The PFS HR value was estimated through a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial population differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted.

Scenario analyses included applying the mosun HRs to the weighted (adjusted) ZUMA-5 24-month data to most accurately reflect the MAIC, applying mosun HR values to axi-cel 48-month follow-up data, and incorporating recent axi-cel health state utility values in diffuse large B-cell lymphoma patients.

The results revealed that compared to mosun, axi-cel showed estimated increases of 1.82 life years (LY) and 1.89 quality-adjusted life years (QALY). Patients receiving axi-cel experienced a PFS of 6.42 LY, compared to 1.60 LY for those on mosun.

The analysis indicated a $257,113 increase in costs during the progression-free state, primarily due to one-time axi-cel treatment expenses. Axi-cel incurred total incremental costs of $204,377, resulting in an incremental cost-effectiveness ratio (ICER) of $108,307 per QALY gained. OWSA produced ICERs ranging from $240,255 to $75,624, with the majority falling below the $150,000/QALY threshold.

In PSA, axi-cel demonstrated a 64% probability of being cost-effective over 5,000 iterations, using a $150,000 willingness-to-pay threshold. Scenarios 1 and 2 yielded ICERs of $105,353 and $102,695, respectively.

The study concluded that axi-cel proves to be cost-effective in comparison to mosun, aligning with the commonly cited $150,000/QALY US willingness-to-pay threshold. The findings remained robust across various sensitivity analyses, effectively addressing parameter uncertainty.

Funding was received from Kite Pharma, Inc.

Source: https://pubmed.ncbi.nlm.nih.gov/38855109/

Oluwole OO, Ray MD, Zur RM, et al. (2024). “Cost-effectiveness of treating relapsed or refractory 3L+ follicular lymphoma with axicabtagene ciloleucel vs mosunetuzumab in the United States.” Front Immunol. 2024 May 24;15:1393939. doi: 10.3389/fimmu.2024.1393939. PMID: 38855109; PMCID: PMC11157123.

ARG Signature Prognosis & Treatment Promise in DLBCL

KEY TAKEAWAYS

  • The study aimed to investigate the role of anoikis in patients with DLBCL, shedding light on its implications for metastasis and aggressiveness.
  • Researchers noticed that the ARG-based signature offers a promising avenue for improving prognosis prediction and treatment optimization.

Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B-cell lymphoma (DLBCL).

Mingze Guan and the team aimed to fill this gap by investigating the significance of anoikis in DLBCL.

Researchers performed an inclusive analysis utilizing RNA sequencing data and matched clinical information sourced from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in the GSE10846 training cohort and subsequently validated in 3 additional cohorts. Furthermore, the half-maximal inhibitory concentration (IC50) of drugs was predicted using a bioinformatics method, and the actual IC50 values for some chemotherapy drugs were obtained via cytotoxicity assay.

About the study results, the high-risk group, as determined by the signature, demonstrated a correlation with poorer prognosis and an immunosuppressive environment in DLBCL. Additionally, the nomogram based on 8 variables displayed superior prognostic forecasting ability compared to the international prognostic index in DLBCL.

Prediction of IC50 indicated heightened sensitivity to doxorubicin (1), IPA-3 (2), lenalidomide (3), gemcitabine (4), and CEP.701 (5) in patients with DLBCL classified as high-risk by the signature, while those in the low-risk group showed sensitivity to cisplatin (6) and dasatinib (7). Consistent with the prediction, the cytotoxicity assay affirmed higher sensitivity to doxorubicin and gemcitabine and lower sensitivity to dasatinib in the high-risk group in DLBCL.

The study concluded that the ARG-based signature offers a promising direction for enhancing prognosis prediction and optimizing treatment strategies for patients with DLBCL.

This study was sponsored by National Natural Science Foundation of China, Doctoral Startup Scientific Research Foundation of Liaoning Province and 1+X program for clinical competency enhancement-improvement of MDT project, Dalian Medical University.

Source: https://pubmed.ncbi.nlm.nih.gov/38709202/

Guan M, Zhao H, Zhang Q, et al. (2024). “A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma.” Expert Rev Mol Diagn. 2024 May;24(5):439-457. doi: 10.1080/14737159.2024.2351465. Epub 2024 May 11. PMID: 38709202.

VIEW ALL

SELECT ONCOLOGY JOURNAL ARTICLES

Optimization Strategies in CAR T-cell Therapy: A Comprehensive Evaluation of Cytopenia, HLH/MAS, and Other Adverse Events

Optimization Strategies in CAR T-cell Therapy: A Comprehensive Evaluation of Cytopenia, HLH/MAS, and Other Adverse Events

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for various hematological malignancies. Still, its remarkable efficacy is accompanied by unique adverse events that must be carefully managed. This comprehensive literature review …

American Journal of Clinical Oncology

Efficacy of Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: A Comprehensive Systematic Review and Meta-analysis

Efficacy of Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: A Comprehensive Systematic Review and Meta-analysis

Objectives: Breast cancer is the most diagnosed cancer in women, with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) being the predominant subtype. Sacituzumab govitecan (SG), a novel antibody-drug conjugate, has emerged as a promising …

American Journal of Clinical Oncology

Bevacizumab Combination Therapy Versus Standard Chemotherapy for Ovarian Cancer in Shorter and Longer Follow-Up Duration: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Bevacizumab Combination Therapy Versus Standard Chemotherapy for Ovarian Cancer in Shorter and Longer Follow-Up Duration: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective: This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period. Methods: We searched Medline, Cochrane CENTRAL, Scopus, and Google …

American Journal of Clinical Oncology