Abstract
Multi-center real world analysis of treatment outcomes of non-COVALENT btki, pirtobrutinib, in patients with COVALENT btki relapsed/refracdtory Mantle Cell Lymphoma
Blood, Vol.146(Supplement 1), pp.5351-5351
11/03/2025
DOI: 10.1182/blood-2025-5351
Abstract
Introduction: cBTKi have made a substantial impact in pts w/ MCL, but pts who develop PD while on treatment w/ cBTKi have historically had poor responses to subsequent lines of therapy (LOT). Brexucel, lisocel, and the non-covalent BTKi pirto have been approved in this population. While two RW studies have substantiated the benefit of brexucel, similar data for pirto are lacking. Accordingly, we aimed to evaluate the outcomes of pts treated w/ pirto in the RW setting.
Methods: We performed a multi-center retrospective cohort study of adult pts w/ a diagnosis of MCL who experienced PD after any approved cBTKi and subsequently received pirto. Pts who received pirto w/ bridging intent and those who switched to pirto due to intolerance of cBTKi were excluded. The 95% exact binomial confidence intervals (CI) were calculated for overall response rate (ORR) and complete response rate (CRR). Progression-free survival (PFS) and overall survival (OS) were defined as the time from pirto start to PD or death, whichever occurred first, and the time from pirto start to death, respectively, and calculated w/ the Kaplan-Meier method. The log-rank test was used to compare survival curves. A multivariate (MV) Cox proportional hazard model was built to calculate adjusted hazard ratio (aHR). Analyses were performed w/ SAS, version 9.4.
Results: Data on 111 pts w/ MCL treated across 21 institutions were collected. Median (mdn) age was 72 (range 33 – 93) years. Twenty-seven pts (24%) were female, 3 (3%) were Asian, 5 (5%) Black, 9 (8%) Hispanic, 86 (77%) White. Among the 53 (48%) pts w/ available MIPI-c at diagnosis, 28 (53%) pts were high-risk. Ki67 at diagnosis was available in 84 (76%) pts: of those, 58 (69%) had a Ki67 ≥30%, and 41 (49%) ≥50%. TP53 mutational status was available in 70 (63%) pts: 33 (47%) had documented TP53 mutation and 10/52 (19%) pts had a disease w/ complex karyotype. Pts had a mdn of 3 (range 1 – 9) prior LOT (n=106). Ninety-one pts (86%) received chemo-immunotherapy (CIT), 16 (15%) autologous stem cell transplant, 19 (18%) venetoclax (ven), 29 (27%) chimeric antigen receptor T-cell, 4 (4%) allogeneic stem cell transplant. For cBTKi, 39 (35%) pts received ibrutinib, 56 (50%) pts acalabrutinib, 33 (30%) pts zanubrutinib, and 17 (15%) pts received more than one cBTKi. The mdn time from the last dose of cBTKi to pirto start was 55 (range 0 – 2587) days, w/ 51 (46%) pts who switched from a cBTKi directly to pirto. Thirty (27%) pts had no response (stable disease or PD as best response) to cBTKi, and 40 (36%) pts had no response to the last LOT. Two (2%) pts received pirto in combination w/ CIT, 8 (7%) w/ an anti-CD20 monoclonal antibody (mAb), 11 (10%) w/ ven ± a mAb, while 86 (77%) pts as single agent. In 104 (94%) pts, pirto was given at full dose, 10 (9%) pts had a subsequent dose reduction. A total of 35 serious (grade ≥3) adverse events (AE) were documented in 27 (24%) pts: 4 (4%) pts had a serious bleeding AE, 5 (5%) pts a serious cardiac AE, 10 (9%) a serious GI AE, and 16 (14%) a serious infectious AE. Ninety-eight (88%) pts were evaluable for response. The ORR was 40% (95% CI 30% – 50%) w/ a CRR of 29% (95% CI 20%– 39%). At the last follow-up, 29 (26%) pts remained on pirto w/ a mdn treatment duration of 15.1 months (range 0.4 – 26). Fifty-eight (52%) pts died, 35 (78%) because of PD. At a mdn follow-up of 15.8 (range 0.4 – 26) months among survivors, the mdn PFS was 4.7 months (95% CI 3.3 – 8.2) and the mdn OS was 13 months (95% CI 9.2 – not available). Using the log-rank test, age (quartile groups), number of LOT (1-2 vs. 3-4 vs. 5+), time from cBTKi to pirto (quartile groups), Ki67≥30%, and high MIPI-C did not result in a statistically significant difference in PFS (p>0.05). Presence of TP53 mutation was associated w/ a non-statistically significant adverse trend in PFS (p=0.0585). No response to cBTKi and Ki67≥50% were associated w/ a statistically significant inferior PFS in log-rank test (p=<0.05), which persisted in a MV Cox regression model (aHR 2.4, 95% CI 1.4-4.2, and aHR 2.6, 95% CI 1.6-4.4, respectively).
Conclusions: This is the first RW report on pirto in MCL pts. In this high-risk population, ORR to pirto was comparable to the BRUIN trial, while PFS was significantly worse, especially in pts w/ no response to cBTKi and w/ a high Ki67. However, prolonged remissions were seen in a subset of pts, suggesting that a better characterization of this population w/ durable benefit from pirto is needed.
Details
- Title: Subtitle
- Multi-center real world analysis of treatment outcomes of non-COVALENT btki, pirtobrutinib, in patients with COVALENT btki relapsed/refracdtory Mantle Cell Lymphoma
- Creators
- Paolo Lopedote - City Of Hope National Medical CenterAdrienne Nedved - Rochester Institute of TechnologyLu Chen - City Of Hope National Medical CenterMarcus Watkins - Saint Louis UniversityArian Roua - Nemours Children's ClinicMuhamad Alhaj Moustafa - lymphoma epidemiology of outcomes consortium (Iowa), Iowa City, United StatesSeyi Abidoye - Scottsdale Community CollegeYun Choi - The Ohio State UniversityGeorgios Pongas - University of MiamiTony Zhuang - The University of Texas MD Anderson Cancer CenterJean Clement - University of VirginiaMegan Searssmith - Levine Cancer InstituteLaura Sun - Emory UniversityHannah Willis - Huntsman Cancer InstituteBrad Kahl - Saint Louis UniversityDavid Bond - The Ohio State UniversityJavier Munoz - lymphoma epidemiology of outcomes consortium (Iowa), Iowa City, United StatesIzidore S. Lossos - Miami UniversityCraig Portell - University of VirginiaMichael Wang - The University of Texas MD Anderson Cancer CenterNilanjan Ghosh - Levine Cancer InstituteJonathon Cohen - Emory UniversityPeter Martin - Outcomes Research ConsortiumJeremy Abramson - Massachusetts General HospitalAnne Beaven - University of North Carolina at Chapel HillPatrick Reagan - University of RochesterDaniel Ermann - Huntsman Cancer InstituteTaylor Brooks - Cleveland ClinicAshlee Joseph - Kettering UniversityNazila Shafagati - University of BaltimoreDaniel McLoughlin - Midwestern UniversityKira Rosenlind - Oregon Health & Science UniversityBrian Hill - Cleveland ClinicNina Wagner-Johnston - University of BaltimoreAnita Kumar - Kettering UniversityUmar Farooq - University of IowaReem Karmali - Midwestern State UniversityTanaya Shree - Oregon Health & Science UniversityMatthew Lunning - University of Nebraska at OmahaStacy Pak - City Of Hope National Medical CenterAlexey Danilov - City Of Hope National Medical CenterYucai Wang - Outcomes Research ConsortiumTycel Phillips - City Of Hope National Medical Center
- Resource Type
- Abstract
- Publication Details
- Blood, Vol.146(Supplement 1), pp.5351-5351
- DOI
- 10.1182/blood-2025-5351
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Publisher
- Elsevier Inc; AMSTERDAM
- Language
- English
- Date published
- 11/03/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985116170502771
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