Time to progression of mantle cell lymphoma after high‐dose cytarabine‐based regimens defines patients risk for death

Visco, Carlo; Tisi, Maria Chiara; Evangelista, Andrea; Rocco, Alice Di; Zoellner, Anna-Katharina; Zilioli, Vittorio Ruggero; Hohaus, Stefan; Sciarra, Roberta; Re, Alessandro; Tecchio, Cristina; Chiappella, Annalisa; Morello, Lucia; Gini, Guido; Nassi, Luca; Perrone, Tommasina; Molinari, Anna Lia; Fabbri, Alberto; Cox, Maria Christina; Finolezzi, Erica; Ferrero, Simone; Puccini, Benedetta; Celis, Maria Isabel Alvarez De; Arcari, Annalisa; Marino, Dario; Merli, Michele; Piazza, Francesco; Gentile, Massimo; Pelosini, Matteo; Loseto, Giacomo; Hermine, Olivier; Dreyling, Martin; Ruggeri, Marco; Martelli, Maurizio; Hoster, Eva; Vitolo, Umberto; Linfomi, Fondazione Italiana

doi:10.1111/bjh.15643

Cited by 56 publications

(50 citation statements)

References 11 publications

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“…With this update of the MCL01 study we can confirm the efficacy of the HyperCVAD‐AM regimen without ASCT, as an active frontline regimen for young patients with MCL (≤65 years). Interestingly, we were able to confirm that patients experiencing early relapse share a high risk of death, similar to what was observed for follicular lymphoma, marginal and more recently mantle cell lymphoma, 15 and treatment of this group of patients (POD24) represents an unmet clinical need. Even if randomised comparison with more commonly recommended strategies (immunochemotherapy plus ASCT consolidation) is lacking, we believe that HyperCVAD‐AM should still be considered one of the available options.…”

Section: Discussionsupporting

confidence: 79%

Long‐term results of the MCL01 phase II trial of rituximab plus HyperCVAD alternating with high‐dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma

et al. 2020

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Summary Mantle cell lymphoma is a rare and incurable lymphoproliferative disorder. In the MCL01 trial, patients were treated with the R‐HCVAD regimen [rituximab plus HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; R‐CVAD) alternating with high‐dose methotrexate and cytarabine (AM)] for four cycles followed by autologous stem cell transplantation (ASCT) for those who reached only a partial response. After a median follow‐up of 10·5 years, we reported 10‐year progression‐free and overall survival rates of 35% and 61% respectively, with a 10‐years cumulative incidence rate of second malignancies of 10·6%. Mature results of the MCL01 trial confirmed the efficacy of HyperCVAD‐AM as a frontline regimen for younger patients (≤65 years).

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Section: Discussionsupporting

confidence: 79%

Long‐term results of the MCL01 phase II trial of rituximab plus HyperCVAD alternating with high‐dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma

et al. 2020

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“…It has been observed that early POD following frontline therapy in younger MCL patients is an independent predictor for inferior survival at time of relapse, and this cohort had superior outcomes receiving second-line ibrutinib compared to chemotherapy. [12][13] In our study early POD was associated with inferior PFS and OS, but this association was lost in multivariable analysis indicating in our more heterogeneous population other variables were more predictive of survival.…”

Section: Discussionmentioning

confidence: 46%

Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real‐world analysis of outcomes in 211 patients

et al. 2021

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Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse. We aimed to investigate outcomes and tolerability for ibrutinib when given second line in a real-world setting. Our multicentre retrospective analysis included 211 R/R MCL patients, median age 73 years, receiving ibrutinib second-line within the United Kingdom's National Health Service. Overall response to ibrutinib was 69% (complete response 27%). The median progression-free survival (PFS) was 17Á8 months (95% CI 13Á1-22Á2) and median overall survival (OS) 23Á9 months (95% CI 15Á0-32Á8). Drug-related adverse event led to dose reduction in 10% of patients and discontinuation in 5%. In patients with progressive disease, accounting for 100 of 152 patients stopping ibrutinib, 43% received further systemic therapy. Post-ibrutinib rituximab, bendamustine and cytarabine (R-BAC) showed a trend toward improved survival compared to alternative systemic treatments (post-ibrutinib median OS 14Á0 months, 95% CI 8Á1-19Á8, vs. 3Á6 months, 95% CI 2Á6-4Á5, P = 0Á06). Our study confirms the clinical benefit and good tolerability of ibrutinib at first relapse in a real-world population. Patients progressing on ibrutinib had limited survival but outcomes with R-BAC in select patients were promising.

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“…Achievement of complete remission (CR) by CT or PET-CT has been repeatedly correlated with longer PFS [101]. Interestingly, time to progression is a strong, independent prognostic factor in patients with R/R MCL [102]. Minimal residual disease (MRD) is detection of a residual disease clone, which is not detectable by standard restaging procedures including CT, PET-CT, or trephine biopsy.…”

Section: Prognostic Factors During and After Inductionmentioning

confidence: 99%

Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma

Klener

2019

IJMS

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Mantle cell lymphoma (MCL) is a heterogeneous malignancy with a broad spectrum of clinical behavior from indolent to highly aggressive cases. Despite the fact that MCL remains in most cases incurable by currently applied immunochemotherapy, our increasing knowledge on the biology of MCL in the last two decades has led to the design, testing, and approval of several innovative agents that dramatically changed the treatment landscape for MCL patients. Most importantly, the implementation of new drugs and novel treatment algorithms into clinical practice has successfully translated into improved outcomes of MCL patients not only in the clinical trials, but also in real life. This review focuses on recent advances in our understanding of the pathogenesis of MCL, and provides a brief survey of currently used treatment options with special focus on mode of action of selected innovative anti-lymphoma molecules. Finally, it outlines future perspectives of patient management with progressive shift from generally applied immunotherapy toward risk-stratified, patient-tailored protocols that would implement innovative agents and/or procedures with the ultimate goal to eradicate the lymphoma and cure the patient.

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Time to progression of mantle cell lymphoma after high‐dose cytarabine‐based regimens defines patients risk for death

Cited by 56 publications

References 11 publications

Long‐term results of the MCL01 phase II trial of rituximab plus HyperCVAD alternating with high‐dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma

Long‐term results of the MCL01 phase II trial of rituximab plus HyperCVAD alternating with high‐dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma

Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real‐world analysis of outcomes in 211 patients

Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma

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