Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients
dc.contributor.author | Zangari, Maurizio | en_US |
dc.contributor.author | Aujay, Monette | en_US |
dc.contributor.author | Zhan, Fenghuang | en_US |
dc.contributor.author | Hetherington, Kristina L. | en_US |
dc.contributor.author | Berno, Tamara | en_US |
dc.contributor.author | Vij, Ravi | en_US |
dc.contributor.author | Jagannath, Sundar | en_US |
dc.contributor.author | Siegel, David | en_US |
dc.contributor.author | Keith Stewart, A. | en_US |
dc.contributor.author | Wang, Luhua | en_US |
dc.contributor.author | Orlowski, Robert Z. | en_US |
dc.contributor.author | Belch, Andrew | en_US |
dc.contributor.author | Jakubowiak, Andrzej J. | en_US |
dc.contributor.author | Somlo, George | en_US |
dc.contributor.author | Trudel, Suzanne | en_US |
dc.contributor.author | Bahlis, Nizar | en_US |
dc.contributor.author | Lonial, Sagar | en_US |
dc.contributor.author | Singhal, Seema | en_US |
dc.contributor.author | Kukreti, Vishal | en_US |
dc.contributor.author | Tricot, Guido | en_US |
dc.date.accessioned | 2011-11-10T15:31:07Z | |
dc.date.available | 2012-07-12T17:42:23Z | en_US |
dc.date.issued | 2011-06 | en_US |
dc.identifier.citation | Zangari, Maurizio; Aujay, Monette; Zhan, Fenghuang; Hetherington, Kristina L.; Berno, Tamara; Vij, Ravi; Jagannath, Sundar; Siegel, David; Keith Stewart, A.; Wang, Luhua; Orlowski, Robert Z.; Belch, Andrew; Jakubowiak, Andrzej; Somlo, George; Trudel, Suzanne; Bahlis, Nizar; Lonial, Sagar; Singhal, Seema; Kukreti, Vishal; Tricot, Guido (2011). "Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients." European Journal of Haematology 86(6). <http://hdl.handle.net/2027.42/86807> | en_US |
dc.identifier.issn | 0902-4441 | en_US |
dc.identifier.issn | 1600-0609 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/86807 | |
dc.description.abstract | The ubiquitin–proteasome pathway regulates bone formation through osteoblast differentiation. We analyzed variation alkaline phosphatase (ALP) during carfilzomib treatment. Data from 38 patients enrolled in the PX‐171‐003 and 29 patients in PX‐171‐004 studies, for patients with relapsed/refractory myeloma, were analyzed. All patients received 20 mg/m 2 of carfilzomib on Days 1, 2, 8, 9, 15, and 16 of a 28‐day cycle. Sixty‐seven patients from ALP data were evaluable. In PX‐171‐003, the ORR (>PR) was 18% and the clinical benefit response (CBR; >MR) was 26%, while in PX‐171‐004, the ORR was 35.5% overall and 57% in bortezomib‐naive patients. ALP increment from baseline was statistically different in patients who achieved ≥VGPR compared with all others on Days 1 ( P = 0.0049) and 8 ( P = 0.006) of Cycle 2. In patients achieving a VGPR or better, ALP increased more than 15 units per liter at Cycle 2 Day 1 over baseline. An ALP increase over the same period of time was seen in 26%, 13% and 11% of patients achieving PR, MR, and SD, respectively. This retrospective analysis of patients with relapsed or refractory myeloma treated with single‐agent carfilzomib indicates that early elevation in ALP is associated with subsequent myeloma response. | en_US |
dc.publisher | Blackwell Publishing Ltd | en_US |
dc.publisher | Wiley Periodicals, Inc. | en_US |
dc.subject.other | Multiple Myeloma | en_US |
dc.subject.other | Alkaline Phosphatase | en_US |
dc.subject.other | Carfilzomib | en_US |
dc.title | Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Oncology and Hematology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Myeloma Program, University of Michigan Cancer Center, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationother | Division of Hematology, University of Utah, Blood/Marrow Transplant and Myeloma Program, Salt Lake City, UT, USA | en_US |
dc.contributor.affiliationother | Department of Cancer Biology, Stem Cent Rx, LLC, South San Francisco, CA, USA | en_US |
dc.contributor.affiliationother | Department of Hematology and Clinical Immunology, University of Padua, Padua, Italy | en_US |
dc.contributor.affiliationother | BMT and Leukemia Program, Washington University, St Louis, MO, USA | en_US |
dc.contributor.affiliationother | Department of Hematology, Mount Sinai Medical Center, New York, NY, USA | en_US |
dc.contributor.affiliationother | Myeloma Division, John Theuer Cancer Center, Hackensack, NJ, USA | en_US |
dc.contributor.affiliationother | Mayo Clinic, Phoenix/Scottsdale, Scottsdale, AZ, USA | en_US |
dc.contributor.affiliationother | MD Anderson Cancer Center, Houston, TX, USA | en_US |
dc.contributor.affiliationother | University of Alberta, Edmonton, Canada | en_US |
dc.contributor.affiliationother | City of Hope National Medical Center, Duarte, CA, USA | en_US |
dc.contributor.affiliationother | Princess Margaret Hospital, Toronto, Canada | en_US |
dc.contributor.affiliationother | Division of Hematology, University of Calgary, Calgary, Canada | en_US |
dc.contributor.affiliationother | Winship Cancer Institute of Emory University, Atlanta, GA, USA | en_US |
dc.contributor.affiliationother | Multiple Myeloma Program, Northwestern University Medical School/Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA | en_US |
dc.identifier.pmid | 21477075 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/86807/1/j.1600-0609.2011.01602.x.pdf | |
dc.identifier.doi | 10.1111/j.1600-0609.2011.01602.x | en_US |
dc.identifier.source | European Journal of Haematology | en_US |
dc.identifier.citedreference | Pearse RN, Sordillo EM, Yaccoby S, Wong BR, Liau DF, Colman N, Michaeli J, Epstein J, Choi Y. Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci USA 2001; 98: 11581 – 6. | en_US |
dc.identifier.citedreference | Giuliani N, Rizzoli V, Roodman GD. Multiple myeloma bone disease: pathophysiology of osteoblast inhibition. Blood 2006; 108: 3992 – 6. | en_US |
dc.identifier.citedreference | Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr. The role of the Wnt‐signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003; 349: 2483 – 94. | en_US |
dc.identifier.citedreference | Garrett IR, Chen D, Gutierrez G, et al. Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J Clin Invest 2003; 111: 1771 – 82. | en_US |
dc.identifier.citedreference | Mukherjee S, Raje N, Schoonmaker JA, et al. Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Invest 2008; 118: 491 – 504. | en_US |
dc.identifier.citedreference | Pennisi A, Li X, Ling W, Khan S, Zangari M, Yaccoby S. The proteasome inhibitor, bortezomib suppresses primary myeloma and stimulates bone formation in myelomatous and nonmyelomatous bones in vivo. Am J Hematol 2009; 84: 6 – 14. | en_US |
dc.identifier.citedreference | Munemasa S, Sakai A, Kuroda Y, Okikawa Y, Katayama Y, Asaoku H, Kubo T, Shimose S, Kimura A. Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation. Int J Oncol 2008; 33: 129 – 36. | en_US |
dc.identifier.citedreference | Breitkreutz I, Raab MS, Vallet S, et al. Lenalidomide inhibits osteoclastogenesis, survival factors and bone‐remodeling markers in multiple myeloma. Lenalidomide, bortezomib inhibit osteoclasts in MM. Leukemia 2008; 22: 1925 – 32. | en_US |
dc.identifier.citedreference | Zangari M, Esseltine D, Lee CK, et al. Response to bortezomib in associated to osteoblastic activation in patients with multiple myeloma. Br J Haematol 2005; 131: 71 – 3. | en_US |
dc.identifier.citedreference | Zangari M, Esseltine D, Cavallo F, Neuwirth R, Elice F, Burns MJ, Yaccoby S, Richardson P, Sonneveld P, tricot G. Predictive value of alkaline phosphatase for response and time to progression in bortezomib‐treated multiple myeloma patients. Am J Hematol 2007; 82: 831 – 3. | en_US |
dc.identifier.citedreference | San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008; 359: 906 – 17. | en_US |
dc.identifier.citedreference | Delforge M, Kropff M, Spicka I, et al. VMP results in fewer bone events and greater ALP increases versus MP in the VISTA study in front‐line MM. Clin Lymphoma Myeloma 2009; 9: S43 (abstr A246). | en_US |
dc.identifier.citedreference | Suzuki E, Demo S, Arastu‐Kapur S, Kirk CJ, Bennett MK. Bortezomib‐resistant cell lines have increased proteasome levels but remain sensitive to carfilzomib. Blood 2009; 114: 2852 (abstract). | en_US |
dc.identifier.citedreference | Deleu S, Lemaire M, Arts J, et al. Bortezomib alone or in combination with the histone deacetylase inhibitor JNJ‐26481585: effect on myeloma bone disease in the 5T2MM murine model of myeloma. Cancer Res 2009; 69: 5307 – 11. | en_US |
dc.identifier.citedreference | De Matteo M, Brunetti AE, Maiorano E, Cafforio P, Dammacco F, Silvestris F. Constitutive down‐regulation of Osterix in osteoblasts from myeloma patients: in vitro effect of Bortezomib and Lenalidomide. Leuk Res 2010; 34: 243 – 9. | en_US |
dc.identifier.citedreference | Zangari M, Yaccoby S, Pappas L, et al. A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients. Haematologica 2011; 96: 333 – 6. | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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