Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

Robak, Tadeusz; Jin, Jie; Pylypenko, Halyna; Verhoef, Gregor; Siritanaratkul, Noppadol; Drach, Johannes; Raderer, Markus; Mayer, Jiřı́; Pereira, Juliana; Tumyan, Gayane; Okamoto, Rumiko; Nakahara, Susumu; Hu, Peter; Appiani, Carlos; Nemat, Sepideh; Cavalli, Franco; Hoof, A. van; Sheliga, Adriana; Teixeira, Adriana; Tomita, Akihiro; Rocafiguera, Albert Oriol; Suvorov, Alexander; Kuzmin, Alexy; Khojasteh, Ali; Mézlini, Amel; Голенков, А К; Bosly, André; Belch, Andrew R.; Velde, Ann Van de; Illes, A.; Mukhopadhyay, Ashis; Meddeb, Balkis; Prijck, Bernard De; Garichochea, Bernardo; Ündar, Bülent; Gabarrón, Caballero; Cao, Carmen; Souza, Cármino Antonio De; Farber, Charles M.; Suh, Cheol Won; Burcoveanu, C; Cebotaru, C.; Truica, Cristina-Ligia; Maruyama, Dai; Belada, David; Yehuda, Dina Ben; Udovitsa, Dmitry; Dolores,; Morra, Enrica; Späth‐Schwalbe, E.; González‐Barca, Eva; Osmanov, Evgenii A.; Capote, Francisco; Offner, Fritz; Cárdenas, Gálvez; Heß, Georg; Manikhas, Georgii; Babu, Govind; Rekhtman, Grigoriy; Rossi, Guiseppe; Marques, Herlander; Bumbea, Horia; Wang, Huaqing; Huang, Huiqiang; Choi, Ilseung; Bulavina, Irina; Lysenko, Irina B.; Avivi, Irit; Kryachok, Iryna; Zaucha, Jan Maciej; Novák, Jan; Díaz, Joaquín; Demeter, Judit; Alexeeva, Julia; Zhu, Jun; Vilchevskaya, Kateryna; Ishizawa, Kenichi; Mauricio, Kenny; Tobinai, Kensei; Ando, Kiyoshi; Abdulkadryrov, Kudrat; Shih, Lee‐Yung; Kuzina, Lyudmila; Gümüş, Mahmut; Wit, Maike de; Capra, Marcelo; Marques, Margarida; Golubeva, Marina; Ojeda-Uribe, Mario; Kyselyova, Maryna; Taniwaki, Masafumi; Federico, Massimo; Crump, Michael; Baccarani, Michele; Ogura, Michinori; Egyed, Miklós; Udvardy, M.; Kurosawa, Mitsutoshi; Uike, Naokuni; Khuageva, Nuriet K.; Shpilberg, Ofer; Gladkov, Oleg; Samoilova, Olga; Serduk, Olga; Santi, Patrícia Xavier; Zachée, Pierre; Kaplan, Polina; Stoia, Răzvan; Gressin, Rémy; Arranz, Reyes; Greil, Richard; Grosicki, Sebastian; Cancelado, Sergio; Nair, Sreejith G.; Gouill, Steven Le; Steenweghen, Steven Van; Yoon, Sung‐Soo; Chuncharune, Suporn; Scheider, Tatiana; Shimoyama, Tatsu; Liu, Ting; Kinoshita, Tomohiro; Uchida, Toshiki; Bunworasate, Udomsak; Vitolo, Umberto; Pavlov, Viacheslav; Phooshkooru, V. R.; Lima, Vladimir C.; Merkulov, Vladimir I.; Nawarawong, Weerasak; Hong, Xin; Ke, Xiaoyan; Terui, Yasuhito; Goh, Yeow Tee; Maeda, Yoshiharu; Shi, Yuankai; Dunaev, Yuri; Lorie, Yurii; Wang, Zhao; Shen, Zhi-Xiang; Borbényi, Zita; Gasztonyi, Zoltán; Masliak, Zvenyslava

doi:10.1016/s1470-2045(18)30685-5

Cited by 93 publications

(46 citation statements)

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“…Studies evaluated : Twelve studies of recently approved drugs for indolent non-Hodgkin’s, relapsed/refractory setting of non-DLBCL and Hodgkin’s lymphoma were evaluated (table 5). 46–62…”

Section: Resultsmentioning

confidence: 99%

EHA evaluation of the ESMO—Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies

et al. 2020

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ObjectiveValue frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology—Magnitude of Clinical Benefit Scale (ESMO-MCBS).MethodsHere we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies.ResultsIn general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described.ConclusionsBased on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials.

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Section: Resultsmentioning

confidence: 99%

EHA evaluation of the ESMO—Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies

et al. 2020

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“…Promising overall survival results were obtained from adding bortezomib to the R‐CHOP regimen compared to R‐CHOP alone in a randomized study, but an increase in hematologic toxicity was noted . Recently, a 5 year follow up study on the lenalidomide with rituximab combination was reported.…”

Section: Advances In the Treatment Of MCLmentioning

confidence: 99%

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

2019

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Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX‐11 expression. Cyclin‐D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki‐67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long‐term follow‐up on chemo‐immunotherapy studies has demonstrated durable remissions in some patients; however, long‐term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy‐free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine‐microenvironmental milieu, incorporation of positron emission tomography‐computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next‐generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.

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“…A more recent paper examined the effect of replacing vincristine with bortezomib in R-CHOP therapy (VR-CAP) for previously untreated patients with MCL unsuitable for bone marrow transplantation as part of a large, randomized, phase III LYM-3002 study (Table 4 ) [ 117 – 120 ]. Eligible patients were randomized to receive six to eight 21-day cycles of R-CHOP or VR-CAP.…”

Section: Mantle Cell Lymphomamentioning

confidence: 99%

“…Similar differences were noted in the median time to next therapy: 44.5 vs. 24.8 months, respectively ( p < 0.001). In addition, with a median follow-up of 82 months, median OS improved significantly, and was approximately 3 years longer in the VR-CAP (90.7 months) than the R-CHOP group (55.7 months; p = 0.001) [ 120 ]. Serious AEs were observed in 38% of the patients treated with VR-CAP and 30% of the patients treated with R-CHOP.…”

Section: Mantle Cell Lymphomamentioning

confidence: 99%

Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later

Robak

2019

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Bortezomib is a dipeptidyl boronic acid that selectively inhibits the ubiquitin proteasome pathway, which plays a role in the degradation of many intracellular proteins. It is the first-in-class selective and reversible inhibitor of the 26S proteasome, with antiproliferative and antitumor activity. It exerts its anti-neoplastic action mainly via the inhibition of the nuclear factor-κB pathway components associated with cell proliferation, apoptosis, and angiogenesis. The drug has revolutionized the treatment of multiple myeloma and, more recently, mantle cell lymphoma. In 2003, bortezomib received accelerated approval from the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma and in 2008 for patients with previously untreated multiple myeloma. In 2006, bortezomib was approved for the treatment of refractory/relapsed mantle cell lymphoma and, in 2014, for previously untreated mantle cell lymphoma. Bortezomib has also demonstrated clinical efficacy both as a single drug and in combination with other agents in light chain amyloidosis, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, and peripheral T-cell lymphomas. Furthermore, continued clinical studies are required to confirm its value for patients with indolent and aggressive B-cell non-Hodgkin lymphomas and acute leukemias.

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Cited by 93 publications

References 28 publications

EHA evaluation of the ESMO—Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies

EHA evaluation of the ESMO—Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later

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