NOVEL THERAPIES FOR RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA POST BRUTON’S TYROSINE KINASE INHIBITOR: A TARGETED LITERATURE REVIEW
Author(s)
Nissen Weisman, RPh, PharmD, Andrea Lo-Rossi, PhD, Chia-Wei Lin, PhD, Carolina Reyes, PhD;
Genentech, Inc., South San Francisco, CA, USA
Genentech, Inc., South San Francisco, CA, USA
OBJECTIVES: We identified therapies evaluated in adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL) post-Bruton’s tyrosine kinase inhibitor (BTKi) to assess the evolving treatment landscape.
METHODS: A targeted literature review was conducted to assess R/R MCL post-BTKi global phase 2 and 3 trials. Exclusions included preclinical studies and non-English publications. Conference abstracts and databases (PubMed, Embase, Cochrane) were searched from 2016-2025. Screening and data extraction were performed by a single reviewer using an AI-enabled tool called Nested Knowledge, validated by human review.
RESULTS: Of 578 records, 17 studies were included after full-text review, and 12 studies reported outcomes. Five ongoing studies without outcomes reported are evaluating ixazomib, odronextamab, and rocbrutinib. All studies that reported outcomes were phase 2. Drugs evaluated included antibody-drug conjugates (ADCs) (zilovertamab, polatuzumab + obinutuzumab), bispecific antibodies (BsAbs) (mosunetuzumab-based, glofitamab), noncovalent BTKi (ncBTKi) (pirtobrutinib), chimeric antigen receptor T-cell (CAR-T) (brexucabtagene, lisocabtagene, tisagenlecleucel), ViPOR regimen (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide), proteasome inhibitor (PI) (carfilzomib). ADCs (n = 9-40) showed a 40% overall response rate (ORR), 11.1-13% complete response (CR), 3 months median duration of response (mDOR), 3.4 months median progression-free survival (mPFS), and 9 months median overall survival (mOS). BsAbs (n = 25-31) demonstrated 44-88% ORR, 24-79% CR, 10.3-12.6 months mDOR, 3.7-19 months mPFS, and 7.3-21 months mOS. NcBTKi (n = 35-52) showed 52-62.9% ORR, 11.4% CR, 6.8 months mPFS, 15.5 months mOS. CAR-T therapies (n = 10-83) reported 80-93% ORR, 67-72% CR, 15.7 months mDOR, 3.2-15.3 months mPFS, and 9.4-18.2 months mOS. ViPOR regimen (n = 8) reported 87.5% ORR and CR. PI demonstrated 18.75% ORR and 6.25% CR.
CONCLUSIONS: Preliminary data indicate promising but heterogenous results within drug classes. Interpretation is limited by small sample sizes and differences in study design, underscoring the need for further investigation in this area of high unmet need.
METHODS: A targeted literature review was conducted to assess R/R MCL post-BTKi global phase 2 and 3 trials. Exclusions included preclinical studies and non-English publications. Conference abstracts and databases (PubMed, Embase, Cochrane) were searched from 2016-2025. Screening and data extraction were performed by a single reviewer using an AI-enabled tool called Nested Knowledge, validated by human review.
RESULTS: Of 578 records, 17 studies were included after full-text review, and 12 studies reported outcomes. Five ongoing studies without outcomes reported are evaluating ixazomib, odronextamab, and rocbrutinib. All studies that reported outcomes were phase 2. Drugs evaluated included antibody-drug conjugates (ADCs) (zilovertamab, polatuzumab + obinutuzumab), bispecific antibodies (BsAbs) (mosunetuzumab-based, glofitamab), noncovalent BTKi (ncBTKi) (pirtobrutinib), chimeric antigen receptor T-cell (CAR-T) (brexucabtagene, lisocabtagene, tisagenlecleucel), ViPOR regimen (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide), proteasome inhibitor (PI) (carfilzomib). ADCs (n = 9-40) showed a 40% overall response rate (ORR), 11.1-13% complete response (CR), 3 months median duration of response (mDOR), 3.4 months median progression-free survival (mPFS), and 9 months median overall survival (mOS). BsAbs (n = 25-31) demonstrated 44-88% ORR, 24-79% CR, 10.3-12.6 months mDOR, 3.7-19 months mPFS, and 7.3-21 months mOS. NcBTKi (n = 35-52) showed 52-62.9% ORR, 11.4% CR, 6.8 months mPFS, 15.5 months mOS. CAR-T therapies (n = 10-83) reported 80-93% ORR, 67-72% CR, 15.7 months mDOR, 3.2-15.3 months mPFS, and 9.4-18.2 months mOS. ViPOR regimen (n = 8) reported 87.5% ORR and CR. PI demonstrated 18.75% ORR and 6.25% CR.
CONCLUSIONS: Preliminary data indicate promising but heterogenous results within drug classes. Interpretation is limited by small sample sizes and differences in study design, underscoring the need for further investigation in this area of high unmet need.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO147
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology