Abstract:
Botezomib-based induction is highly effective for the treatment of newly diagnosed multiple myeloma (NDMM). We investigated the outcomes of NDMM patients who failed to respond to bortezomib-based induction in a real-life clinical setting. In a cohort of 295 consecutive NDMM patients in 3 medical centers, 74 (25%) failed to achieve at least partial response after 4 induction cycles, and were classified as non-responsive. Compared to induction responders, they were older, more frequently anemic, had a higher incidence of del17p and ISS-3, and a worse performance status. In multivariable analysis, bortezomib-based induction failure occurred in 25% of patients and was the strongest independent factor predicting mortality with a 5-fold hazard ratio (95% CI 1.44-8.68). Three-year overall survival in responsive vs. non-responsive patients were 76% vs. 53%, respectively (p < 0.0001). Survival from time of salvage second-line treatment was significantly shorter among induction non-responders vs. responders (25 months vs. not-reached, p = 0.024). © 2015 Taylor & Francis.
Notes:
Cited By :2Export Date: 18 February 2017References: Moreau, P., Richardson, P.G., Cavo, M., Proteasome inhibitors in multiple myeloma: 10 years later (2012) Blood, 120, pp. 947-959;Harousseau, J.L., Attal, M., Avet-Loiseau, H., Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: Results of the IFM 2005-01 phase III trial (2010) J Clin Oncol, 28, pp. 4621-4629;
Sonneveld, P., Schmidt-Wolf, I.G.H., Van Der Holt, B., Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: Results of the randomized phase III HOVON-65/GMMG-HD4 trial (2012) J Clin Oncol, 30, pp. 2946-2955;
San Miguel, J.F., Schlag, R., Khuageva, N.K., Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma (2008) N Engl J Med, 359, pp. 906-917;
Niesvizky, R., Flinn, I.W., Rifkin, R., Efficacy and safety of three bortezomib-based combinations in elderly, newly diagnosed multiple myeloma patients: Results from all randomized patients in the community-based, phase 3b UPFRONT study (2011) Blood, 118. , Abstract 478;
Palumbo, A., Bringhen, S., Rossi, D., Bortezomib-melphalan-prednisone-Thalidomide followed by maintenance with bortezomib-Thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: A randomized controlled trial (2010) J Clin Oncol, 28, pp. 5101-5109;
Reeder, C.B., Reece, D.E., Kukreti, V., Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: High response rates in a phase II clinical trial (2009) Leukemia, 23, pp. 1337-1341;
Durie, B.G.M., Harousseau, J.-L., Miguel, J.S., International uniform response criteria for multiple myeloma (2006) Leukemia, 20, pp. 1467-1473;
Bassan, R., Hoelzer, D., Modern therapy of acute lymphoblastic leukemia (2011) J Clin Oncol, 29, pp. 532-543;
Evens, A.M., Kostakoglu, L., The role of fdg-pet in defining prognosis of hodgkin lymphoma for early-stage disease (2015) Hematology Am Soc Hematol Educ Program, 124, pp. 135-143;
Murray, M.Y., Auger, M.J., Bowles, K.M., Overcoming bortezomib resistance in multiple myeloma (2014) Biochem Soc Trans, 42, pp. 804-808;
Greipp, P.R., Miguel, J.S., Dune, B.G.M., International staging system for multiple myeloma (2005) J Clin Oncol, 23, pp. 3412-3420;
Zhuang, J., Da, Y., Li, H., Cytogenetic and clinical risk factors for assessment of ultra high-risk multiple myeloma (2014) Leuk Res, 38, pp. 188-193;
Chng, W.J., Dispenzieri, A., Chim, C.-S., IMWG consensus on risk stratification in multiple myeloma (2014) Leukemia, 28, pp. 269-277;
Ludwig, H., Miguel, J.S., Dimopoulos, M., International Myeloma Working Group recommendations for global myeloma care (2014) Leukemia, 28, pp. 981-992;
Moreau, P., Avet-Loiseau, H., Facon, T., Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma (2011) Blood, 118, pp. 5752-5758;
Cavo, M., Tacchetti, P., Patriarca, F., Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: A randomised phase 3 study (2010) Lancet, 376, pp. 2075-2085;
Cavo, M., Rajkumar, S.V., Palumbo, A., International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation (2011) Blood, 117, pp. 6063-6073;
Benboubker, L., Dimopoulos, M.A., Dispenzieri, A., Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma (2014) N Engl J Med, 371, pp. 906-917;
Palumbo, A., Magarotto, V., Bringhen, S., A randomized phase 3 trial of melphalan-lenalidomide-prednisone (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) vs. Lenalidomide plus dexamethasone (Rd) in elderly newly diagnosed multiple myeloma patients (2013) Blood, 122. , Abstract 536;
Hideshima, T., Richardson, P., Chauhan, D., The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells (2001) Cancer Res, 61, pp. 3071-3076;
Landis-Piwowar, K.R., Milacic, V., Chen, D., The proteasome as a potential target for novel anticancer drugs and chemosensitizers (2006) Drug Resist Update, 9, pp. 263-273;
Palumbo, A., Rajkumar, S.V., San Miguel, J.F., International myeloma working group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation (2014) J Clin Oncol, 32, pp. 587-600;
Hari, P., Vij, R., Zhang, M.J., Non-response to initial MM induction-is there benefit to additional therapy to upgrade response pre-Transplant (AHCT (2013) Clin Lymphoma Myeloma Leuk, 13, p. S115
Website
