Originally published as JCO Early Release 10.1200/JCO.2008.17.9721 on November 10 2008

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Influence of Pre- and Post-Transplantation Responses on Outcome of Patients With Multiple Myeloma: Sequential Improvement of Response and Achievement of Complete Response Are Associated With Longer Survival

Juan José Lahuerta, Maria Victoria Mateos, Joaquin Martínez-López, Laura Rosiñol, Anna Sureda, Javier de la Rubia, José García-Laraña, Rafael Martínez-Martínez, Miguel T. Hernández-García, Dolores Carrera, Joan Besalduch, Felipe de Arriba, José María Ribera, Lourdes Escoda, Belén Hernández-Ruiz, Javier García-Frade, Concepción Rivas-González, Adrían Alegre, Joan Bladé, Jesús F. San Miguel

From the Hospital Universitario 12 de Octubre; Hospital Universitario Ramón y Cajal; Clínico San Carlos; and Hospital Universitario de la Princesa, Madrid; Hospital Universitario de Salamanca, Centro de Investigación del Cáncer–Instituto de Biolia Molecula y Celular del Cancer de Salamanca (Universidad de Salemanca-Centros Superior de Investigaciones Aèntîficas) Salamanca; Hospital Clinic, Institut d’Investigacions Biomédiques August Pi I Sunyer; Hospital de la Santa Creu i Sant Pau, Barcelona; Hospital La Fe, Valencia; Hospital Universitario de Canarias, Canarias; Hospital Central de Asturias, Asturias; Complejo Asistencial Son Dureta, Palma de Mallorca; Hospital General Morales Messeguer, Murcia; Hospital Gemans Trias I Pujol, Badalona; Hospital Joan XXIII, Tarragona; Hospital Nuestra Señora de Alarcos, Ciudad Real; Hospital del Rio Ortega, Valladolid; and Hospital General Universitario, Alicante, Spain

Corresponding author: Jesús F. San-Miguel, MD, PhD, Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain; e-mail: sanmigiz{at}usal.es

Purpose Complete response (CR) is considered an important goal in most hematologic malignancies. However, in multiple myeloma (MM), there is no consensus regarding whether immunofixation (IF)-negative CR, IF-positive near-CR (nCR), and partial response (PR) are associated with different survivals. We evaluated the prognostic influence on event-free survival (EFS) and overall survival (OS) of these responses pre- and post-transplantation in newly diagnosed patients with MM.

Patients and Methods We analyzed 632 patients from the prospective Grupo Español de Mieloma 2000 protocol who were uniformly treated with vincristine, carmustine, cyclophosphamide, melphalan, and predisone/vincristine, carmustine, adryamcine, and dexamethasone induction followed by high-dose therapy and autologous stem-cell transplantation.

Results Post-transplantation response markedly influenced outcomes. Patients achieving CR had significantly longer EFS (median, 61 v 40 months; P < 10^–5) and OS (medians not reached; P = .01) versus patients achieving nCR, who likewise had somewhat better outcomes compared with patients achieving PR (median EFS, 34 months, P = .07 v nCR; median OS, 61 months, P = .04). EFS and OS and influence of response were similar among older (age 65 to 70 years) and younger (age < 65 years) patients. Similar findings were observed with pretransplantation response, with trends toward EFS (P = .1; P = .05) and OS (P = .1; P = .07) benefit in patients achieving CR versus nCR and PR, respectively. Post-transplantation response was markedly influenced by pretransplantation response; improvements in response were associated with prolonged survival.

Conclusion Quality of response post-transplantation, notably CR, is significantly associated with EFS and OS prolongation in newly diagnosed patients with MM. There were trends toward similar associations with pretransplantation response status.

published online ahead of print at www.jco.org on November 10, 2008.

Supported by Grant No. PI051284 from the Fondo de Investigación Sanitaria, Instituto Carlos III, Ministerio de Sanidad, Cooperative Research Thematic Network (Grant No. RD06/0020/0006; M.M.J., S.L.F.) and Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (Grants No. PI060339 and 02/0905).

Written on behalf of the Grupo Español de Mieloma and the Programa Español de Tratamientos en Hematología

Presented at the XIth International Myeloma Workshop and IVth International Workshop on Waldenström's Macroglobulinemia, June 25-30, 2007, Kos Island, Greece.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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