Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression

doi:10.3324/haematol.12106

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Multiple Myeloma

Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression

María-Victoria Mateos¹^,*, José M. Hernández²^,*, Miguel T. Hernández³^,*, Norma C. Gutiérrez¹^,*, Luis Palomera⁴^,*, Marta Fuertes⁵^,*, Pedro Garcia-Sanchez⁶^,*, Juán J. Lahuerta⁷^,*, Javier de la Rubia⁸^,*, María-José Terol⁹^,*, Ana Sureda¹⁰^,*, Joan Bargay¹¹^,*, Paz Ribas¹²^,*, Adrian Alegre¹³^,*, Felipe de Arriba¹⁴^,*, Albert Oriol¹⁵^,*, Dolores Carrera¹⁶^,*, José García-Laraña¹⁷^,*, Ramón García-Sanz¹^,*, Joan Bladé¹⁸^,*, Felipe Prósper¹⁹^,*, Gemma Mateo¹^,*, Dixie-Lee Esseltine¹⁰, Helgi van de Velde²¹, Jesús F. San Miguel¹^,*^,+

¹ Hospital Universitario de Salamanca;
² Hospital General de Segovia
³ Hospital Universitario de Canarias
⁴ Hospital Lozano Blesa de Zaragoza
⁵ Hospital Virgen Blanca de León
⁶ Hospital Clínico Universitario San Carlos de Madrid
⁷ Hospital 12 de Octubre de Madrid
⁸ Hospital La Fe de Valencia
⁹ Hospital Clinico Universitario de Valencia
¹⁰ Hospital Santa Creu i Sant Pau de Barcelona
¹¹ Hospital Sont Llatzer de Palma de Mallorca
¹² Hospital Dr Pesset de Alicante
¹³ Hospital la Princesa de Madrid
¹⁴ Hospital Morales Messeguer de Murcia
¹⁵ Hospital Germans Trials I Pujol de Badalona
¹⁶ Hospital Central de Asturias
¹⁷ Hospital Ramón y Cajal de Madrid
¹⁸ Hospital Clinic. IDIBAPS. Barcelona, Spain
¹⁹ Clínica Universitaria de Navarra
^* PETHEMA/GEM (Grupo Español de MM), Spain
⁺ University Hospital, CIC/CSIC Salamanca, Spain
²⁰ Millennium Pharmaceuticals, Inc., Cambridge, MA, USA and
²¹ Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium

Correspondence: Jesús F. San Miguel, Paseo San Vicente 58-182, 37007 Salamanca, Spain. E-mail: sanmigiz{at}usal.es

Background: New treatment options offering enhanced activity in elderly,newly diagnosed patients with multiple myeloma are required.One strategy is to combine melphalan and prednisone with novelagents. We previously reported an 89% response rate, including32% complete responses and 11% near complete responses, in ourphase 1/2 study of bortezomib plus melphalan and prednisone(VMP) in 60 newly diagnosed multiple myeloma patients with amedian age of 75 years. Here, we report updated time-to-eventsdata and the impact of poor prognosis factors on outcome.

Design and Methods: Updated analyses of time to biochemical progression and overallsurvival with VMP were conducted, and compared with those ofhistorical controls treated with melphalan and prednisone. Aunivariate analysis was performed to evaluate the influenceof known prognostic factors on the time to progression.

Results: After a median follow-up of 26 months, the median time to progressionwith VMP was 27.2 months, compared with 20.0 months with melphalanplus prednisone. The median overall survival with VMP was notreached versus 26 months with melphalan and prednisone; thesurvival rate at 38 months was 85% versus 38%, respectively.Time to progression was not significantly affected by elevatedβ₂-microglobulin or lactate dehydrogenase levels, advancedage, or cytogenetic abnormalities, but was shorter in patientswith albumin <3 g/dL, Karnofsky performance status $≤$ 70%, bonemarrow plasma cell infiltration $≥$ 40%, and, particularly, highplasma cell proliferative activity ( $≥$ 2.5% S-phase cells).

Conclusions: VMP is highly active and well tolerated in elderly patientswith newly diagnosed muktiple myeloma, with 85% of patientsalive at 3 years. Moreover, VMP may overcome the poor prognosticimpact of various factors, particularly cytogenetic abnormalities.

Key words: multiple myeloma, bortezomib, melphalan, prednisone, elderly, clinical trial, first-line.