Novel chemotherapy‐free combination regimen for ibrutinib‐resistant mantle cell lymphoma

Srour, Samer A.; Lee, Hun J.; Nomie, Krystle; Ye, Haige; Chen, Wendy; Oriabure, Onyekachukwu; Romaguera, Jorge; Wang, Michael L.

doi:10.1111/bjh.14669

Cited by 10 publications

(6 citation statements)

References 10 publications

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“…Bortezomib has also been studied in combination with rituximab and dexamethasone, with an ORR of 81% (44% CR) and a median PFS of 12 months [52]. Finally, the combination of rituximab, bortezomib, lenalidomide, and dexamethasone has been reported to be feasible and clinically active in a small series of heavily pretreated MCL patients sequenced after BTKi treatment [53], and in the authors' experience has been a generally well tolerated and effective chemotherapy free regimen in this setting. However, it should be noted that the combination of lenalidomide and bortezomib has been studied in a prospective study which reported a high incidence of treatment discontinuation due to AEs and the toxicity profile is such that this combination would not be favored prior to BTKi treatment [54].…”

Section: Lenalidomide and Bortezomibmentioning

confidence: 85%

Relapsed Mantle Cell Lymphoma: Current Management, Recent Progress, and Future Directions

Bond

Martin

Maddocks

2021

JCM

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The increasing number of approved therapies for relapsed mantle cell lymphoma (MCL) provides patients effective treatment options, with increasing complexity in prioritization and sequencing of these therapies. Chemo-immunotherapy remains widely used as frontline MCL treatment with multiple targeted therapies available for relapsed disease. The Bruton’s tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib, and zanubrutinib achieve objective responses in the majority of patients as single agent therapy for relapsed MCL, but differ with regard to toxicity profile and dosing schedule. Lenalidomide and bortezomib are likewise approved for relapsed MCL and are active as monotherapy or in combination with other agents. Venetoclax has been used off-label for the treatment of relapsed and refractory MCL, however data are lacking regarding the efficacy of this approach particularly following BTKi treatment. Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies have emerged as highly effective therapy for relapsed MCL, with the CAR-T treatment brexucabtagene autoleucel now approved for relapsed MCL. In this review the authors summarize evidence to date for currently approved MCL treatments for relapsed disease including sequencing of therapies, and discuss future directions including combination treatment strategies and new therapies under investigation.

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Section: Lenalidomide and Bortezomibmentioning

confidence: 85%

Relapsed Mantle Cell Lymphoma: Current Management, Recent Progress, and Future Directions

Bond

Martin

Maddocks

2021

JCM

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“…42 A subsequent report suggested that the combination of dexamethasone, rituximab, lenalidomide, and bortezomib was active in this setting. 43 Importantly, both series reported low rates of treatment-emergent toxicity, which is particularly relevant to a population being treated for mainly palliative purposes. Patients who have highly treatment-resistant disease (to both chemotherapy and ibrutinib) appear to have poor outcomes after ibrutinib failure, and clinicians need to carefully consider whether intensive therapy and its associated toxicity is consistent with a palliative approach.…”

Section: Most Patients With MCL Have Poor Outcomes After Ibrutinib Failurementioning

confidence: 97%

Optimizing therapy for mantle cell lymphoma

Martin

2017

Hematology

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Most people with mantle cell lymphoma (MCL) present with diffuse adenopathy and benefit from early initiation of rituximab and high-dose cytarabine- or bendamustine-based therapies. Some patients, however, present with primarily nonnodal disease that can follow either an indolent or a rapidly progressive, treatment-resistant clinical course. Rarely, patients present with explosive disease that can be challenging to manage and often involves the central nervous system. New agents with improved therapeutic indices facilitate treatment while maintaining quality of life, but also present new complications at the time of treatment failure. Although uncommon presentations are not new to clinicians who treat MCL, the increasing clarity of underlying biology and prognostic implications may help us develop more specialized treatment strategies.

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“…However, the combination of rituximab, bortezomib, lenalidomide, and dexamethasone (DR2IVE) was reported to be generally well-tolerated and was active in a very small population of heavily pretreated MCL patients sequenced after BTKi treatment. A median of 2 cycles was received, with an ORR of 100% in 3 out of 5 patients still alive at the last follow-up, ranging from 3 to 11 months [ 67 ]. A trial with a larger sample size is needed to better understand the safety and efficacy of this regimen after BTKi treatment.…”

Section: Beyond Btk Inhibitors: Combination Therapiesmentioning

confidence: 99%

Relapsed/Refractory Mantle Cell Lymphoma: Beyond BTK Inhibitors

Burkart

Karmali

2022

JPM

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Mantle cell lymphoma (MCL) is a rare mature B-cell non-Hodgkin lymphoma (B-NHL) with historically poor outcomes. Virtually all patients will eventually experience refractory or relapsed (R/R) disease, with a virulent course of resistance and serial relapses, making treatment challenging. The available therapies for R/R MCL are not curative with conventional therapy, their goal being to palliate and prolong survival. A variety of agents approved for R/R MCL, including Bruton’s tyrosine kinase inhibitors (BTKi), changed the treatment landscape of R/R MCL. In the pre-BTKi era, the median progression-free survival (PFS) in R/R disease was 4–9 months. With the introduction of ibrutinib, the median PFS improved to 13–14.6 months. Despite these impressive results, the duration of response is limited, and resistance to BTKi inevitably develops in a subset of patients. Outcomes after progression on BTKi are extremely poor, with a median overall survival (OS) of 6 to 10 months. Certain therapies, such as chimeric antigen receptor (CAR) T cells, have shown promising results after BTKi failure. The preferred combination and sequencing of therapies beyond BTKi remain unestablished and are currently being investigated. In this review, we describe the current evidence for the available treatment of R/R MCL after progression on BTKi.

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Novel chemotherapy‐free combination regimen for ibrutinib‐resistant mantle cell lymphoma

Cited by 10 publications

References 10 publications

Relapsed Mantle Cell Lymphoma: Current Management, Recent Progress, and Future Directions

Relapsed Mantle Cell Lymphoma: Current Management, Recent Progress, and Future Directions

Optimizing therapy for mantle cell lymphoma

Relapsed/Refractory Mantle Cell Lymphoma: Beyond BTK Inhibitors

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