High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants

Abstract

One hundred and thirty-five patients with advanced and refractory myeloma received one of three high-dose therapy regimens: melphalan at doses of 90 to 100 mg/m2 (MEL 100; 47 patients) without autotransplant; total body irradiation (TBI; 850 cGy) with either melphalan 140 mg/m2 or thiotepa 750 mg/m2 and autologous bone marrow transplant (ABMT) (< or = 30% plasma cells; 21 patients); melphalan 200 mg/m2 (MEL 200) supported by both peripheral blood stem cells (PBSC) and ABMT plus GM- CSF intended as a double-transplant program (67 patients; 42 have completed and 3 are still awaiting a second autotransplant; 5 additional patients received an allograft for their second transplant). Mortality within 2 months of therapy was 20% to 25% with MEL 100 and TBI regimens, but less than 1% with MEL 200, mainly because severe neutropenia (< 500/microL) was shortened to less than 1 week due to infusion of PBSC and use of growth factor therapy. Low beta 2- microglobulin (beta 2M) levels < or = 2.5 mg/L and MEL 200 therapy were identified as the two most important independent favorable variables associated with prolonged event-free survival (EFS) and overall survival (OS). On the basis of these two parameters, three risk groups were defined: 29 good-risk patients with low beta 2M receiving MEL 200 had the best outcome, with median durations of EFS of 37 months and projected OS of > or = 43 months; 54 intermediate-risk patients displaying one of the two favorable parameters had EFS and OS durations of 16 and 36 months, respectively; and 52 poor-risk patients with high beta 2M not receiving MEL 200 had a dismal prognosis, with EFS of 3 months and OS of 5 months (all P > .0001). Further analysis that excluded treatment as a variable identified high beta 2M and resistant relapse as the two major adverse prognostic factors, one of which was present in 80% of the 135 patients. Among these 108 high-risk patients, prognosis was improved markedly with MEL 200 because of both better supportive care (PBSC and hematopoietic growth factors) and more intensive therapy using the double-transplant approach. This study supports the concept that safer and potentially more-effective therapies can be developed in the setting of advanced and resistant disease.

Conventional induction treatments do not influence overall survival in multiple myeloma

“…These have led to a higher rate of complete remission than conventional chemotherapy (1-3% v 50%), but no cure (Corradini et al, 1995) and all patients finally relapse. These reports contain little information about the strategy, for instance a second transplantation (Vesole et al, 1994), or the regimens used.…”

A combination of anti‐interleukin 6 murine monoclonal antibody with dexamethasone and high‐dose melphalan induces high complete response rates in advanced multiple myeloma

“…To improve the response rates and especially the CR rates which are correlated with survival ( Vesole et al , 1994; Samuels & Bitran, 1995) without increasing the toxicity, we have investigated a new approach, i.e. the combination of high‐dose therapy HDM220 with anti‐IL‐6 murine mAb and DXM.…”

VAD or VMBCP in multiple myeloma refractory to or relapsing after cyclophosphamide–prednisone therapy (protocol MY 85)

“…The poor results with these two regimens led to other therapies for these patients: high‐dose chemotherapy ( Vesole et al , 1994 ), allogeneic bone marrow transplantation ( Garhton et al , 1991 ), use of cytokines or anti‐cytokines alone or in association with chemotherapy ( Avvisati et al , 1995 ), modulation of multidrug resistance ( Sonneveld et al , 1992 ).…”