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Multicenter Study
. 2023 Aug;202(4):749-759.
doi: 10.1111/bjh.18519. Epub 2022 Oct 18.

Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study

Georg Hess  1 , Martin Dreyling  2 , Lucie Oberic  3 , Eva Gine  4 , Pier Luigi Zinzani  5 , Kim Linton  6 , Adam Vilmar  7 , Mats Jerkeman  8 , Jenny M H Chen  9 , Anke Ohler  1 , Stephan Stilgenbauer  10 , Catherine Thieblemont  11 , Jonathan Lambert  12 , Vittorio Ruggero Zilioli  13 , Juan-Manuel Sancho  14 , Ana Jiménez-Ubieto  15 , Luca Fischer  2 , Toby A Eyre  16 , Sam Keeping  9 , Julie E Park  9 , James J Wu  17 , Rubina Siddiqi  17 , John Reitan  18 , Sally Wade  19 , Gilles Salles  20
Affiliations
Multicenter Study

Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study

Georg Hess et al. Br J Haematol. 2023 Aug.

Abstract

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6-20.0) in the overall cohort, 5.5 months (95% CI 3.9-8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9-30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3-12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure.

Keywords: Bruton tyrosine kinase inhibitor; mantle cell lymphoma; post-BTKi; real-world evidence; survival.

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Conflict of interest statement

Conflicts of interest

GH has received research support for the submitted work from Kite, a Gilead Company; has received grants or contracts from Celgene, Kite, a Gilead Company, Incyte, Janssen, Morphosys, Pfizer, and Roche; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, ADC, AstraZeneca, Genmab, Kite, a Gilead Company, Incyte, Janssen, Morphosys, Novartis, Roche, and Takeda; has received support for attending meetings and/or travel from Kite, a Gilead Company, and Janssen; and has participated in on a Data Safety Monitoring Board or Advisory Board for Miltenyie. LO has received support for attending meetings and/or travel from Roche and AstraZeneca; and has participated on a Data Safety Monitoring Board or Advisory Board for Roche and Gilead Sciences. PLZ has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Takeda, Gilead Sciences, Sanofi, Incyte, Novartis, Merck, Bristol-Myers Squibb (BMS), AstraZeneca, and Kyowa Kirin. KL has received consulting fees from Genmab, Roche, Kite, a Gilead Company, and Beigene; has received payment or honoraria for educational events from Abbvie and Celgene/BMS; has received support for attending meetings from BMS and Takeda; and has leadership or fiduciary role in NCRI, EHA LyG, WiL, and Epcoritamab Global Council. MJ has received grants or contracts from Roche, Abbvie, and BMS; has received consulting fees from Gilead Sciences, Janssen, and Abbvie; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen; has participated on Data Safety Monitoring board or Advisory Board for GenMab. SS has received grants or contracts; consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; support for attending meetings and/or travel; equipment, materials, drugs, medical, writing, gifts or other services; and payments for participation on a Data Safety Monitoring Board or Advisory Board from AbbVie, Acerta, Amgen, AstraZeneca, BeiGene, BMS, Celgene, Genentech, Gilead Sciences, GSK, Hoffmann-La Roche, Incyte, Infinity, Janssen, Novartis, Pharmacyclics, Sunesis, and Verastem. JL has received payment or honoraria for educational events and support for attending meetings from Kite, a Gilead Company. VRZ has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or education events from Janssen; has received support for attending meetings and/or travel from Janssen; and has participated on Data Safety Monitoring board or Advisory Board for Gilead Sciences and Novartis. JMS has received honoraria for educational events from Roche, Kite, a Gilead Company, Celgene/BMS, Novartis, Janssen, Takeda, and Incyte; has received support for attending meetings and/or travel from Roche; and has received honoraria for participation in Advisory Board from Roche, Kite, a Gilead Company, Celgene/BMS, Novartis, Janssen, Incyte, Beigene, Lilly. TAE has received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Loxo Oncology, Eli Lilly, Beigene, AstraZeneca, Janssen, Incyte, Abbvie, Roche, and Kite, a Gilead Company; has received grants or contracts from AstraZeneca and Beigene; has received consulting fees from Loxo Oncology, Eli Lilly, Beigene, AstraZeneca, Janssen, Incyte, Secura Bio, Abbvie, Roche, and Kite a Gilead Company; and has received payments for travel to scientific congress from Abbvie. JJW is an employee of Kite, a Gilead Company; has received honoraria from the Patient-Centered Outcomes Research Institute (PCORI), both as a member of the Rare Disease Advisory Panel, and as a grants reviewer for the Improving Methods Program; has received travel/meeting support from Kite, a Gilead Company, and Amgen; owns stock in Gilead Sciences, Amgen, Abbott, AbbVie, Pfizer, Roche, Curis, Avid Biosciences, Evofem, Lensar, VBI Vaccines, and Viracta Therapeutics. RS is an employee of Kite, a Gilead Company, and was previously employed by Amgen; has led advisory boarding meeting for Kite, a Gilead Company; and owns stocks in Gilead Sciences and Amgen. SW has received writing support for the submitted work from Kite, a Gilead Company; has received consulting fees from Kite, a Gilead Company, Allergan, Amgen, and Johnson & Johnson; and has received support for attending meetings from Kite, a Gilead Company. GS has received consulting fees from Abbvie, Celgene/BMS, Epizyme, Genmab, Incyte, Janssen, Kite, a Gilead Company, Loxo, Milteniy, Molecular Partners, Morphosys, Nordic Nanovector, Novartis, Rapt, and Takeda; has received payment or honoraria for speaking in symposium from Bayer, Epizyme, and Regeneron; has participated on a Data Safety Monitoring board or Advisory Board for Beigene; and has stock or stock options from Owkin. JMHC, SK, and JEP are employees of PRECISIONheor which received funding for this study from Kite, a Gilead Company. MD, EG, AV, AO, CT, AJU, LF, and JR declare no competing interests.

Figures

Fig 1.
Fig 1.. Patient flow diagram and treatment overview.
The top three most common treatments received are listed in the grey-shaded boxes; treatments were classified into 11 mutually exclusive sub-categories according to the following hierarchy: BTKi regimens, chemotherapies (BR, R-BAC, cytarabine-containing regimen, gemcitabine-containing regimens or other chemotherapy +/− antibodies), targeted therapies (lenalidomide-containing regimens, bortezomib-containing regimens, temsirolimus-containing regimens, and other targeted therapies +/− antibodies), and other treatments such as anti-metabolite, radioimmunotherapy, radiotherapy, or unknown. BR, bendamustine + rituximab; BTKi, Bruton tyrosine kinase inhibitor; CAR, chimeric antigen receptor; MCL, mantle cell lymphoma; R-BAC, rituximab + bendamustine + cytarabine aOne patient had multiple reasons for exclusion
Fig 2.
Fig 2.. Sankey diagram of treatment patterns (from 1L up to 5L).
Treatment patterns of patients from 1L up to 5L (left to right) among 240 patients with relapsed/refractory mantle cell lymphoma who received BTKi between July 2012 to July 2018. The proportions (%) shown are based on total number of patients (N) receiving the preceding line of treatment (except for 1L which is based on 240 patients). 1L, first-line; 2L, second-line; 3L, third-line; 4L, fourth-line; 5L, fifth-line; BR, bendamustine + rituximab; BTKi, Bruton tyrosine kinase inhibitor; MCL, mantle cell lymphoma; R-BAC, rituximab + bendamustine + cytarabine *Others included anti-metabolite, radioimmunotherapy, radiotherapy, or unknown
Fig 3.
Fig 3.. Kaplan-Meier plots of overall survival from initial diagnosis of mantle cell lymphoma.
Tick marks indicate censored data. BTKi, Bruton tyrosine kinase inhibitor; CI, confidence interval
Fig 4.
Fig 4.. Kaplan-Meier plots of overall survival from initiation or discontinuation of treatment for mantle cell lymphoma.
Kaplan-Meier plots of overall survival A) from date of initiation of first BTKi therapy, B) from date of discontinuation of first BTKi therapy, C) from date of initiation of first post-BTKi therapy (among all 149 patients who received post-BTKi therapy), and D) from date of initiation of first post-BTKi therapy, by subgroup based on lines of therapy. Tick marks indicate censored data. BTKi, Bruton tyrosine kinase inhibitor; CI, confidence interval; LOT, lines of prior therapy
See this image and copyright information in PMC

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