Association between quality of response and outcomes in patients with newly diagnosed mantle cell lymphoma receiving VR-CAP versus R-CHOP in the phase 3 LYM-3002 study
Language English Country Italy Media print-electronic
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
28183846
PubMed Central
PMC5477608
DOI
10.3324/haematol.2016.152496
PII: haematol.2016.152496
Knihovny.cz E-resources
- MeSH
- Cyclophosphamide administration & dosage MeSH
- Adult MeSH
- Doxorubicin administration & dosage MeSH
- Remission Induction MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphoma, Mantle-Cell drug therapy pathology MeSH
- Antibodies, Monoclonal, Murine-Derived administration & dosage MeSH
- Prednisone administration & dosage MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Rituximab administration & dosage MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Vincristine administration & dosage MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Names of Substances
- Cyclophosphamide MeSH
- Doxorubicin MeSH
- Antibodies, Monoclonal, Murine-Derived MeSH
- Prednisone MeSH
- Rituximab MeSH
- Vincristine MeSH
In the phase 3 LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered or ineligible for transplant, the median progression-free survival was significantly improved with VR-CAP (24.7 versus 14.4 months with R-CHOP; P<0.001). This post-hoc analysis evaluated the association between the improved outcomes and quality of responses achieved with VR-CAP versus R-CHOP in LYM-3002. Patients were randomized to six to eight 21-day cycles of VR-CAP or R-CHOP. Outcomes included progression-free survival, duration of response (both assessed by an independent review committee), and time to next anti-lymphoma treatment, evaluated by response (complete response/unconfirmed complete response and partial response), MIPI risk status, and maximum reduction of lymph-node measurements expressed as the sum of the product of the diameters. Within each response category, the median progression-free survival was longer for patients given VR-CAP than for those given R-CHOP (complete response/unconfirmed complete response: 40.9 versus 19.8 months; partial response: 17.1 versus 11.7 months, respectively); similarly, the median time to next anti-lymphoma treatment was longer among the patients given VR-CAP than among those treated with R-CHOP (complete response/unconfirmed complete response: not evaluable versus 26.6 months; partial response: 35.3 versus 24.3 months). Within the complete/unconfirmed complete and partial response categories, improvements in progression-free survival, duration of response and time to next anti-lymphoma treatment were more pronounced in patients with low-and intermediate-risk MIPI treated with VR-CAP than with R-CHOP. In each response category, more VR-CAP than R-CHOP patients had a sum of the product of the diameters nadir of 0 during serial radiological assessments. Results of this post-hoc analysis suggest a greater duration and quality of response in patients treated with VR-CAP in comparison with those treated with R-CHOP, with the improvements being more evident in patients with low- and intermediate-risk MIPI. LYM-3002 ClinicalTrials.gov: NCT00722137.
Cherkassy Regional Oncology Center Ukraine
Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand
Hospital das Clinicas da Faculdade de Medicina da USP São Paolo Brazil
Janssen Research and Development High Wycombe Buckinghamshire UK
Janssen Research and Development LLC Raritan NJ USA
Masaryk University Hospital Brno Czech Republic
Medical University of Lodz Copernicus Memorial Hospital Poland
Millennium Pharmaceuticals Inc Boston MA USA
Oncology Institute of Southern Switzerland Ospedale San Giovanni Bellinzona Ticino Switzerland
Sun Yat sen University Cancer Center Guangzhou Guangdong China
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Japan
See more in PubMed
Howlader N, Noone A, Krapcho, et al. SEER Cancer Statistics Review, 1975–2012, National Cancer Institute, Bethesda, MD. Based on November 2014 SEER data submission, posted to the SEER website, April 2015. Available at: http://seer.cancer.gov/csr/1975_2012/ (Accessed July 2015).
Smith A, Crouch S, Lax S, et al. Lymphoma incidence, survival and prevalence 2004–2014: sub-type analyses from the UK’s Haematological Malignancy Research Network. Br J Cancer. 2015;112(9):1575–1584. PubMed PMC
Zhou Y, Wang H, Fang W, et al. Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer. 2008;113(4):791–798. PubMed
Dreyling M, Thieblemont C, Gallamini A, et al. ESMO Consensus Conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol. 2013;24(4):857–877. PubMed
McKay P, Leach M, Jackson R, Cook G, Rule S. Guidelines for the investigation and management of mantle cell lymphoma. Br J Haematol. 2012;159(4):405–426. PubMed
Howard OM, Gribben JG, Neuberg DS, et al. Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol. 2002;20(5):1288–1294. PubMed
European Medicines Agency. European Medicines Agency. VELCADE® (bortezomib). Summary of Product Characteristics (updated February 2014). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000539/WC500048471.pdf (Accessed July 2015). 2014.
Millennium Pharmaceuticals Inc. VEL-CADE® (bortezomib) for injection: for subcutaneous or intravenous use. Full prescribing information. October 2014, Revision 17. Available at: http://www.velcade.com/files/PDFs/VELCADE_PRESCRIBING_INFORMATION.pdf (Accessed July 2015).
Japanese Pharmaceuticals and Medical Devices Agency. List of approved products FY 2015. https://www.pmda.go.jp/files/000208993.pdf.
Robak T, Huang H, Jin J, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015; 372(10):944–953. PubMed
Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–586. PubMed
Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008;111(2):558–565. PubMed
Hoster E, Klapper W, Hermine O, et al. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol. 2014;32(13):1338–1346. PubMed
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32(27):3059–3068. PubMed PMC
Juweid ME, Wiseman GA, Vose JM, et al. Response assessment of aggressive non-Hodgkin’s lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography. J Clin Oncol. 2005;23(21):4652–4661. PubMed
Pott C, Hoster E, Delfau-Larue MH, et al. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood. 2010; 115(16):3215–3223. PubMed PMC
Dreyling M. Haematological cancer: bortezomib in MCL–new standard of care or just another option? Nat Rev Clin Oncol. 2015;12(7):376–378. PubMed
Frosch Z, Luskin MR, Landsburg DJ, et al. R-CHOP or R-HyperCVAD with or without autologous stem cell transplantation for older patients with mantle cell lymphoma. Clin Lymphoma Myeloma Leuk. 2015;15(2):92–97. PubMed
Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381(9873):1203–1210. PubMed
ClinicalTrials.gov
NCT00722137