Double-intensive therapy in high-risk multiple myeloma

Abstract

A high remission rate is achieved with high-dose melphalan (HDM) in multiple myeloma (MM), and autologous transplantation of hematopoietic stem cells allows a prompt hematologic recovery after high-dose therapy. We treated 97 patients with high-risk MM (group 1:44 advanced MM including 14 primary resistances and 30 relapses; group 2: 53 newly diagnosed MM) with a first course of HDM. For responding patients a second course of high-dose therapy with hematopoietic stem cell support was proposed. After the first HDM, the overall response and complete remission rates were 71% and 25% with no significant difference between the two groups. The median durations of neutropenia and thrombocytopenia were significantly longer in group 1 (29.5 days and 32 days, respectively) than in group 2 (23 days and 17 days, respectively). This severe myelosuppression led to eight toxic deaths and the fact that only 38 of the 69 responders could proceed to the second course (three allogenic and 35 autologous transplantations). Among the 35 patients undergoing autologous transplantation (10 in group 1, 25 in group 2), 31 received their marrow unpurged collected after the first HDM, and four received peripheral blood stem cells. The median durations of neutropenia and thrombocytopenia after autologous transplantation were 24 days and 49 days, respectively. Two toxic deaths and nine prolonged thrombocytopenias were observed. The median survival for the 97 patients was 24 months (17 months in group 1, 37 months in group 2) and the median duration of response was 20 months. The only parameters that have a significant impact on the survival are the age (+/- 50 years) and the response to HDM. The median survival of the 35 patients undergoing autologous transplantation is 41 months, but the median duration of remission is 28 months with no plateau of the remission duration curve. Patients responding to HDM may have prolonged survival, but even a second course of high-dose therapy probably cannot eradicate the malignant clone.

Autologous stem cell transplantation after first remission induction treatment in multiple myeloma: A report of the french registry on autologous transplantation in multiple myeloma

“…Patients in apparent CR had a median survival of 67 months versus 33 months for patients who did not achieve CR (and 47 months for patients achieving only PR). In a previous study on double-intensive therapy, we have already shown that the response to the first course of HDM has a great impact on survival [6]. In a pilot study of ABMT for previously untreated patients, one of us also reported that the duration of response was affected by the magnitude of response [4].…”

Presenting Features and Prognosis in 72 Patients With Multiple Myeloma Who Were Younger Than 40 Years

“…The median survival of our patients younger than 40 years who had normal renal function or low serum 2 -microglobulin levels was about 8 years. This long survival in young patients with MM treated with conventional chemotherapy should be considered when evaluating the results in patients receiving more intensive therapy such as bone marrow transplantation (Gahrton et al, 1991;Attal et al, 1992;Harousseau et al, 1992;Jagannath et al, 1992). Patients who also have a low plasma cell labelling index might have an even longer median survival.…”

“…The effect of chemotherapy in MM is palliative and does not usually result in long-lasting responses, even when intensive regimens such as VAD or high-dose melphalan are used (Gore et al, 1989;Samson et al, 1989;Lokhorst et al, 1992). For this reason, the efficacy of high-dose therapy followed by autologous or allogeneic stem cell support is currently being investigated (Gahrton et al, 1991;Attal et al, 1992;Harousseau et al, 1992;Jagannath et al, 1992;Alexanian & Dimopoulos, 1994). Although a median survival of 54 months is the longest reported so far in long-term studies of MM, it is still unsatisfactory, especially in persons younger than 40 years.…”

Pharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant

“…Prolonged severe neutropenia is one of the major adverse effects and dose-limiting toxicities of HDM, which in some patients leads to serious infections and other complications. 6,7 Granulocyte-colony stimulating factor (G-CSF) is given to restore circulating neutrophils after chemotherapyinduced neutropenia in MM, although the timing for starting G-CSF after transplant varies among institutions. 8 Recent studies conducted by our group and prior studies by others have also demonstrated that the G-CSF regimen can significantly influence the duration of neutropenia following ASCT.…”