A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma

A. Larocca, S. Bringhen, Maria T. Petrucci, S. Oliva, A.P. Falcone, T. Caravita, O. Villani, Giulia Benevolo, A. M. Liberati, F. Morabito, V. Montefusco, R. Passera, L. Rosa, P. Omedé, I.D. Vincelli, S. Spada, A.M. Carella, E. Ponticelli, Daniele Derudas, M. Genuardi & 10 others Tommasina Guglielmelli, C. Nozzoli, E. Aghemo, Lorenzo Paoli, C. Conticello, Caterina Musolino, M. Offidani, M. Boccadoro, P. Sonneveld, A. A. Palumbo

Research output: Contribution to journalArticle

Abstract

This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ≥75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ≥3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ≥3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients . © 2016 Macmillan Publishers Limited.
Original languageEnglish
Pages (from-to)1320-1326
Number of pages7
JournalLeukemia
Volume30
Issue number6
DOIs
Publication statusPublished - 2016

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Frail Elderly
Multiple Myeloma
Maintenance
Melphalan
Peripheral Nervous System Diseases
Drug Combinations
Prednisone
Cyclophosphamide
Disease-Free Survival
Bortezomib
Infection
Pharmaceutical Preparations

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A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma. / Larocca, A.; Bringhen, S.; Petrucci, Maria T.; Oliva, S.; Falcone, A.P.; Caravita, T.; Villani, O.; Benevolo, Giulia; Liberati, A. M.; Morabito, F.; Montefusco, V.; Passera, R.; Rosa, L.; Omedé, P.; Vincelli, I.D.; Spada, S.; Carella, A.M.; Ponticelli, E.; Derudas, Daniele; Genuardi, M.; Guglielmelli, Tommasina; Nozzoli, C.; Aghemo, E.; Paoli, Lorenzo; Conticello, C.; Musolino, Caterina; Offidani, M.; Boccadoro, M.; Sonneveld, P.; Palumbo, A. A.

In: Leukemia, Vol. 30, No. 6, 2016, p. 1320-1326.

Research output: Contribution to journalArticle

Larocca, A, Bringhen, S, Petrucci, MT, Oliva, S, Falcone, AP, Caravita, T, Villani, O, Benevolo, G, Liberati, AM, Morabito, F, Montefusco, V, Passera, R, Rosa, L, Omedé, P, Vincelli, ID, Spada, S, Carella, AM, Ponticelli, E, Derudas, D, Genuardi, M, Guglielmelli, T, Nozzoli, C, Aghemo, E, Paoli, L, Conticello, C, Musolino, C, Offidani, M, Boccadoro, M, Sonneveld, P & Palumbo, AA 2016, 'A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma', Leukemia, vol. 30, no. 6, pp. 1320-1326. https://doi.org/10.1038/leu.2016.36
Larocca, A. ; Bringhen, S. ; Petrucci, Maria T. ; Oliva, S. ; Falcone, A.P. ; Caravita, T. ; Villani, O. ; Benevolo, Giulia ; Liberati, A. M. ; Morabito, F. ; Montefusco, V. ; Passera, R. ; Rosa, L. ; Omedé, P. ; Vincelli, I.D. ; Spada, S. ; Carella, A.M. ; Ponticelli, E. ; Derudas, Daniele ; Genuardi, M. ; Guglielmelli, Tommasina ; Nozzoli, C. ; Aghemo, E. ; Paoli, Lorenzo ; Conticello, C. ; Musolino, Caterina ; Offidani, M. ; Boccadoro, M. ; Sonneveld, P. ; Palumbo, A. A. / A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma. In: Leukemia. 2016 ; Vol. 30, No. 6. pp. 1320-1326.
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title = "A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma",
abstract = "This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ≥75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64{\%} with VP, 67{\%} with VCP and 86{\%} with VMP, and very good partial response rate or better was 26{\%}, 28.5{\%} and 49{\%}, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60{\%}, 70{\%} and 76{\%} in VP, VCP, VMP, respectively. At least one drug-related grade ≥3 non-hematologic adverse event (AE) occurred in 22{\%} of VP, 37{\%} of VCP and 33{\%} of VMP patients; the discontinuation rate for AEs was 12{\%}, 14{\%} and 20{\%}, and the 6-month rate of toxicity-related deaths was 4{\%}, 4{\%} and 8{\%}, respectively. The most common grade ≥3 AEs included infections (8-20{\%}), and constitutional (10-14{\%}) and cardiovascular events (4-12{\%}); peripheral neuropathy was limited (4-6{\%}). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients . {\circledC} 2016 Macmillan Publishers Limited.",
author = "A. Larocca and S. Bringhen and Petrucci, {Maria T.} and S. Oliva and A.P. Falcone and T. Caravita and O. Villani and Giulia Benevolo and Liberati, {A. M.} and F. Morabito and V. Montefusco and R. Passera and L. Rosa and P. Omed{\'e} and I.D. Vincelli and S. Spada and A.M. Carella and E. Ponticelli and Daniele Derudas and M. Genuardi and Tommasina Guglielmelli and C. Nozzoli and E. Aghemo and Lorenzo Paoli and C. Conticello and Caterina Musolino and M. Offidani and M. Boccadoro and P. Sonneveld and Palumbo, {A. A.}",
note = "Cited By :2 Export Date: 16 March 2017 CODEN: LEUKE Correspondence Address: Palumbo, A.; Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU), Via Genova, 3, Italy; email: appalumbo@yahoo.com References: Kumar, S.K., Rajkumar, S.V., Dispenzieri, A., Lacy, M.Q., Hayman, S.R., Buadi, F.K., Improved survival in multiple myeloma and the impact of novel therapies (2008) Blood, 111, pp. 2516-2520; Brenner, H., Gondos, A., Pulte, D., Expected long-term survival of patients diagnosed with multiple myeloma in 2006-2010 (2009) Haematologica, 94, pp. 270-275; Altekruse, S.F., Kosary, C.L., Krapcho, M., Neyman, N., Aminou, R., Waldron, W., SEER Cancer Statistics Review, 1975-2007, , http://seer.cancer.gov/csr/19752007/S, Available at (last accessed 10 July 2015; Palumbo, A., Bringhen, S., Mateos, M.V., Larocca, A., Facon, T., Kumar, S.K., Geriatric assessment predicts survival and toxicities in elderly myeloma patients: An International Myeloma Working Group report (2015) Blood, 125, pp. 2068-2074; Bringhen, S., Mateos, M.V., Zweegman, S., Larocca, A., Falcone, A.P., Oriol, A., Age and organ damage correlate with poor survival in myeloma patients: Meta-analysis of 1435 individual patient data from 4 randomized trials (2013) Haematologica, 98, pp. 980-987; San Miguel, J.F., Schlag, R., Khuageva, N.K., Dimopoulos, M.A., Shpilberg, O., Kropff, M., Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma (2008) N Engl J Med, 359, pp. 906-917; Fayers, P.M., Palumbo, A., Hulin, C., Waage, A., Wijermans, P., Beksa{\cc}, M., Thalidomide for previously untreated elderly patients with multiple myeloma: Meta-analysis of 1685 individual patient data from 6 randomized clinical trials (2011) Blood, 118, pp. 1239-1247; San Miguel, J.F., Schlag, R., Khuageva, N.K., Dimopoulos, M.A., Shpilberg, O., Kropff, M., Continued overall survival benefit after 5 years' follow-up with bortezomibmelphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with previously untreated multiple myeloma, and no increased risk of second primary malignancies: Final results of the Phase 3 VISTA Trial [abstract] (2011) Blood, 118; Mateos, M.V., Richardson, P.G., Schlag, R., Khuageva, N.K., Dimopoulos, M.A., Shpilberg, O., Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: Updated follow-up and impact of subsequent therapy in the phase III VISTA trial (2010) J Clin Oncol, 28, pp. 2259-2266; Wijermans, P., Schaafsma, M., Termorshuizen, F., Ammerlaan, R., Wittebol, S., Sinnige, H., Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: The HOVON 49 Study (2010) J Clin Oncol, 28, pp. 3160-3166; Hulin, C., Facon, T., Rodon, P., Pegourie, B., Benboubker, L., Doyen, C., Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial (2009) J Clin Oncol, 27, pp. 3664-3670; Niesvizky, R., Flinn, I.W., Rifkin, R., Gabrail, N., Charu, V., Clowney, B., Communitybased phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens (2015) J Clin Oncol, 33, pp. 3921-3929; Kumar, S., Flinn, I., Richardson, P.G., Hari, P., Callander, N., Noga, S.J., Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma (2012) Blood, 119, pp. 4375-4382; Facon, T., Mary, J.Y., P{\'e}gourie, B., Attal, M., Renaud, M., Sadoun, A., Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high dose therapy (2006) Blood, 107, pp. 1292-1298; Durie, B.G., Kyle, R.A., Belch, A., Bensinger, W., Blade, J., Boccadoro, M., Myeloma management guidelines: A consensus report from the Scientific Advisors of the International Myeloma Foundation (2003) Hematol J, 4, pp. 379-398; Kyle, R.A., Rajkumar, S.V., Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma (2009) Leukemia, 23, pp. 3-9; Lawton, M.P., Scales to measure competence in everyday activities (1988) Psychopharmacol Bull, 24, pp. 609-614; Charlson, M.E., Pompei, P., Ales, K.L., MacKenzie, C.R., A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation (1987) J Chronic Dis, 40, pp. 373-383; Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0, , http://ctep.cancer.gov/protocolDevelopment/electronicapplications/docs/ctcaev3.pdf, National Cancer Institute Available at (accessed 3 January 2015); Simon, R., Optimal two-stage designs for phase II clinical trials (1989) Control Clin Trials, 10, pp. 1-10; Kaplan, E.L., Meier, P., Nonparametric estimation from incomplete observations (1958) J Am Stat Assoc, 53, pp. 457-481; Mateos, M.V., Oriol, A., Mart{\'i}nez-L{\'o}pez, J., Guti{\'e}rrez, N., Teruel, A.I., De Paz, R., Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: A randomised trial (2010) Lancet Oncol, 11, pp. 934-941; Palumbo, A., Bringhen, S., Rossi, D., Cavalli, M., Larocca, A., Ria, R., 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; Mateos, M.V., Oriol, A., Mart{\'i}nez-L{\'o}pez, J., Guti{\'e}rrez, N., Teruel, A.I., L{\'o}pez De La Gui{\'a}, A., Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial (2012) Blood, 120, pp. 2581-2588; Palumbo, A., Hajek, R., Delforge, M., Kropff, M., Petrucci, M.T., Catalano, J., Continuous lenalidomide treatment for newly diagnosed multiple myeloma (2012) N Engl J Med, 366, pp. 1759-1769",
year = "2016",
doi = "10.1038/leu.2016.36",
language = "English",
volume = "30",
pages = "1320--1326",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma

AU - Larocca, A.

AU - Bringhen, S.

AU - Petrucci, Maria T.

AU - Oliva, S.

AU - Falcone, A.P.

AU - Caravita, T.

AU - Villani, O.

AU - Benevolo, Giulia

AU - Liberati, A. M.

AU - Morabito, F.

AU - Montefusco, V.

AU - Passera, R.

AU - Rosa, L.

AU - Omedé, P.

AU - Vincelli, I.D.

AU - Spada, S.

AU - Carella, A.M.

AU - Ponticelli, E.

AU - Derudas, Daniele

AU - Genuardi, M.

AU - Guglielmelli, Tommasina

AU - Nozzoli, C.

AU - Aghemo, E.

AU - Paoli, Lorenzo

AU - Conticello, C.

AU - Musolino, Caterina

AU - Offidani, M.

AU - Boccadoro, M.

AU - Sonneveld, P.

AU - Palumbo, A. A.

N1 - Cited By :2 Export Date: 16 March 2017 CODEN: LEUKE Correspondence Address: Palumbo, A.; Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU), Via Genova, 3, Italy; email: appalumbo@yahoo.com References: Kumar, S.K., Rajkumar, S.V., Dispenzieri, A., Lacy, M.Q., Hayman, S.R., Buadi, F.K., Improved survival in multiple myeloma and the impact of novel therapies (2008) Blood, 111, pp. 2516-2520; Brenner, H., Gondos, A., Pulte, D., Expected long-term survival of patients diagnosed with multiple myeloma in 2006-2010 (2009) Haematologica, 94, pp. 270-275; Altekruse, S.F., Kosary, C.L., Krapcho, M., Neyman, N., Aminou, R., Waldron, W., SEER Cancer Statistics Review, 1975-2007, , http://seer.cancer.gov/csr/19752007/S, Available at (last accessed 10 July 2015; Palumbo, A., Bringhen, S., Mateos, M.V., Larocca, A., Facon, T., Kumar, S.K., Geriatric assessment predicts survival and toxicities in elderly myeloma patients: An International Myeloma Working Group report (2015) Blood, 125, pp. 2068-2074; Bringhen, S., Mateos, M.V., Zweegman, S., Larocca, A., Falcone, A.P., Oriol, A., Age and organ damage correlate with poor survival in myeloma patients: Meta-analysis of 1435 individual patient data from 4 randomized trials (2013) Haematologica, 98, pp. 980-987; San Miguel, J.F., Schlag, R., Khuageva, N.K., Dimopoulos, M.A., Shpilberg, O., Kropff, M., Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma (2008) N Engl J Med, 359, pp. 906-917; Fayers, P.M., Palumbo, A., Hulin, C., Waage, A., Wijermans, P., Beksaç, M., Thalidomide for previously untreated elderly patients with multiple myeloma: Meta-analysis of 1685 individual patient data from 6 randomized clinical trials (2011) Blood, 118, pp. 1239-1247; San Miguel, J.F., Schlag, R., Khuageva, N.K., Dimopoulos, M.A., Shpilberg, O., Kropff, M., Continued overall survival benefit after 5 years' follow-up with bortezomibmelphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with previously untreated multiple myeloma, and no increased risk of second primary malignancies: Final results of the Phase 3 VISTA Trial [abstract] (2011) Blood, 118; Mateos, M.V., Richardson, P.G., Schlag, R., Khuageva, N.K., Dimopoulos, M.A., Shpilberg, O., Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: Updated follow-up and impact of subsequent therapy in the phase III VISTA trial (2010) J Clin Oncol, 28, pp. 2259-2266; Wijermans, P., Schaafsma, M., Termorshuizen, F., Ammerlaan, R., Wittebol, S., Sinnige, H., Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: The HOVON 49 Study (2010) J Clin Oncol, 28, pp. 3160-3166; Hulin, C., Facon, T., Rodon, P., Pegourie, B., Benboubker, L., Doyen, C., Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial (2009) J Clin Oncol, 27, pp. 3664-3670; Niesvizky, R., Flinn, I.W., Rifkin, R., Gabrail, N., Charu, V., Clowney, B., Communitybased phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens (2015) J Clin Oncol, 33, pp. 3921-3929; Kumar, S., Flinn, I., Richardson, P.G., Hari, P., Callander, N., Noga, S.J., Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma (2012) Blood, 119, pp. 4375-4382; Facon, T., Mary, J.Y., Pégourie, B., Attal, M., Renaud, M., Sadoun, A., Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high dose therapy (2006) Blood, 107, pp. 1292-1298; Durie, B.G., Kyle, R.A., Belch, A., Bensinger, W., Blade, J., Boccadoro, M., Myeloma management guidelines: A consensus report from the Scientific Advisors of the International Myeloma Foundation (2003) Hematol J, 4, pp. 379-398; Kyle, R.A., Rajkumar, S.V., Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma (2009) Leukemia, 23, pp. 3-9; Lawton, M.P., Scales to measure competence in everyday activities (1988) Psychopharmacol Bull, 24, pp. 609-614; Charlson, M.E., Pompei, P., Ales, K.L., MacKenzie, C.R., A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation (1987) J Chronic Dis, 40, pp. 373-383; Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0, , http://ctep.cancer.gov/protocolDevelopment/electronicapplications/docs/ctcaev3.pdf, National Cancer Institute Available at (accessed 3 January 2015); Simon, R., Optimal two-stage designs for phase II clinical trials (1989) Control Clin Trials, 10, pp. 1-10; Kaplan, E.L., Meier, P., Nonparametric estimation from incomplete observations (1958) J Am Stat Assoc, 53, pp. 457-481; Mateos, M.V., Oriol, A., Martínez-López, J., Gutiérrez, N., Teruel, A.I., De Paz, R., Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: A randomised trial (2010) Lancet Oncol, 11, pp. 934-941; Palumbo, A., Bringhen, S., Rossi, D., Cavalli, M., Larocca, A., Ria, R., 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; Mateos, M.V., Oriol, A., Martínez-López, J., Gutiérrez, N., Teruel, A.I., López De La Guiá, A., Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial (2012) Blood, 120, pp. 2581-2588; Palumbo, A., Hajek, R., Delforge, M., Kropff, M., Petrucci, M.T., Catalano, J., Continuous lenalidomide treatment for newly diagnosed multiple myeloma (2012) N Engl J Med, 366, pp. 1759-1769

PY - 2016

Y1 - 2016

N2 - This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ≥75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ≥3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ≥3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients . © 2016 Macmillan Publishers Limited.

AB - This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ≥75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ≥3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ≥3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients . © 2016 Macmillan Publishers Limited.

U2 - 10.1038/leu.2016.36

DO - 10.1038/leu.2016.36

M3 - Article

VL - 30

SP - 1320

EP - 1326

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 6

ER -