Nearly all patients will either relapse on or be refractory to 1L therapy, and outcomes worsen with each subsequent line of therapy2

At diagnosis, outcomes are worse in patients with high-risk characteristics3,4

Risk Factor mOS in patients with high-risk characteristics vs patients without
TP53 mutations*

~2× shorter

(42 months vs 80 months, respectively; P<0.0001)

Blastoid morphology*

~3× shorter

(26 months vs 75 months, respectively; P<0.0001)

Ki-67 index ≥30%

3.4 years

with Ki-67 ≥30% vs not reached with Ki-67 <30%

*Data from a real-world study of 4049 patients diagnosed with MCL from 2011 through 2021 and treated with chemotherapy, BTKis, proteasome inhibitors, IMiDs, and Bcl2 inhibitor alone or in combination with other therapies in predominantly community-based oncology practices in the United States. Of 4049 patients, 278 (7%) did not have treatment documented at last follow-up.3

Results of a retrospective analysis of data from 508 patients with MCL registered in either the MCL Elderly trial (aged ≥60 years) or MCL Younger trial (aged <66 years) with Ki-67 index available (median follow-up of 5.7 years). Patients in MCL Younger were treated with HDT + ASCT.4

While evolving therapies have improved outcomes in R/R MCL, relapse is almost universal1,2

of patients

treated with BTKi progress
within 12-18 months5,6§

National Comprehensive Cancer Network® (NCCN®)–suggested regimens for 2L R/R MCL include: covalent BTKis (acalabrutinib, zanubrutinib, ibrutinib), lenalidomide + rituximab, bendamustine + rituximab, R-BAC 500, bortezomib +/- rituximab, GemOx + rituximab, R-DHAP, ibrutinib + venetoclax, venetoclax +/- rituximab, and ibrutinib + rituximab.1

§Data from 2 studies evaluating BTKi therapy in R/R MCL: (1) an open-label, multicenter, phase 3 clinical trial in 280 patients with R/R MCL, who had received ≥1 rituximab-containing treatments, randomized to receive ibrutinib (n=139) or temsirolimus (n=141). The primary efficacy endpoint was PFS. (2) An open-label, single-arm, multicenter, phase 2 clinical trial in 124 patients with R/R MCL who received acalabrutinib. The primary endpoint was overall response (assessed by Lugano classification). PFS was a secondary endpoint.5,6

Following 2L relapse, outcomes are poor

Overall Survival graph Overall Survival graph

Data from a systematic literature review that included studies involving patients who relapsed following 2L, and were treated with non-CAR T-cell therapies in 3L+ R/R MCL.7

There remains a critical need to plan for 2L relapse with a treatment
that can improve responses for patients with R/R MCL2

1L=first-line; 2L=second-line; 3L=third-line; ASCT=autologous stem cell transplantation; Bcl2=B-cell lymphoma 2; BTKi=Bruton’s tyrosine kinase inhibitor; CAR=chimeric antigen receptor; CI=confidence interval; CR=complete response; GemOX=gemcitabine hydrochloride and oxaliplatin; HDT=high-dose chemotherapy; IMiDs=immunomodulatory drugs; MCL=mantle cell lymphoma; mOS=median overall survival; NCCN=National Comprehensive Cancer Network; ORR=objective response rate; PFS=progression-free survival; R-BAC=rituximab, bendamustine, and cytarabine; R-DHAP=rituximab, dexamethasone, cytarabine, and cisplatin; R/R=relapsed or refractory.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas. V.5.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 22, 2023. To view the most recent and complete version of the guideline, go online to 2. Kumar A, Sha F, Toure A, et al. Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse. Blood Cancer J. 2019;9(50):1-10. 3. Narkhede M, Goyal G, Shea L, Mehta A, Giri S. Evaluating real-world treatment patterns and outcomes of mantle cell lymphoma. Blood Adv. 2022;6(14):4122-4131. 4. Hoster E, Rosenwald A, Berger F, et al. Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: results from randomized trials of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2016;34(12):1386-1394. 5. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391:659-667. 6. Dreyling M, Jurczak W, Jerkeman M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387:770-778. 7. Dreyling M, Shah B, Wu J, et al. Unmet need in relapsed/refractory (R/R) mantle cell lymphoma (MCL) post-Bruton tyrosine kinase inhibitor (BTKi): a systematic literature review and meta-analysis. Abstract 603. Abstract presented at the International Conference on Malignant Lymphoma; June 13-17, 2023; Lugano, Switzerland.