Transplant Response May Not Benefit Myeloma
Transplant Response May Not Benefit Myeloma
Abstract & Commentary
By Andrew S. Artz, MD Section of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationships with this field of study.
Synopsis: The results of this study show that HDT intensification, when given to myeloma patients who have responded to the initial chemotherapy, significantly increases the CR rate but has no significant impact on PFS or OS.
Source: Blade J, et al. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood. 2005;106:3755-3759.
Blade and colleagues report a randomized trial for multiple myeloma (MM) comparing high-dose therapy (HDT) and autologous stem cell support compared to non-transplant intensive therapy. Only patients who at least achieved a minor response after 4 cycles of chemotherapy were randomized. Standard therapy consisted of alternating courses of VBMCP/VBAD. Randomized patients in both arms received maintenance interferon and dexamethasone. Among the 164 patients eventually randomized, the complete remission (CR) rate at 6 months was higher for the HDT arm 30% vs 11% (P = .002), but overall survival did not differ (61 months for HDT and 66 months for standard therapy; P = .89). Despite a higher response rate, HDT with autologous stem cell support for patients in response to initial therapy did not enhance compared to intensive chemotherapy and maintenance.
Standard chemotherapy regimens have been disappointing for MM. HDT with autologous stem cell support has shown a significant increase in CR rate and overall survival.1,2 Other series published in abstract form by Barlogie et al and Fermand et al have not supported a benefit from HDT.3,4
PETHEMA, a Spanish cooperative group, report a randomized, controlled trial comparing chemotherapy to intensification with HDT and autologous stem cell support. They enrolled 216 patients aged younger than 70 from May 1994 through October 1999. All patients were initially treated with a chemotherapy regimen of VBMCP (vincristine, BCNU, melphalan, cyclophosphamide, prednisone) alternating with VBAD (vincristine, BCNU, adriamycin, dexamethasone). Patients with at least a minor response after four cycles were randomized to receive either 8 additional courses of VMBCP/VBAD or HDT. In the HDT arm, the preparative regimen consisted of either melphalan 200 mg/m2 or TBI of 12 Gy plus melphalan 14 mg/m2. Stem cell support was with autologous peripherally mobilized progenitor cells. Patients in response to either chemotherapy or HDT received maintenance with interferon and dexamethasone.
One-hundred eighty-five (85%) responded to initial chemotherapy, of whom 164 were eventually randomized. The arms were not completely balanced as more patients in the HDT arm had a hemoglobin < 10 g/dL and IgA subtype. The CR rate of 30% six months after HDT was higher than the 11% CR rate after completion of 12 courses of chemotherapy (P = .002). Ten patients in the chemotherapy arm eventually underwent HDT for relapse while 7 in the HDT arm received a second transplant. Overall survival was similar at 61 months of the HDT arm and 66 months for the chemotherapy arm (P = .89). Survival after relapse was also similar in both arms.
Commentary
The decision to purse HDT and autologous transplant in MM remains challenging. Randomized studies suggest conflicting results, but most clinicians for relatively young or fit patients will consider autologous transplant. Delayed transplantation represents another option. In this randomized study, Blade et al show an increased CR rate but no survival benefit for HDT with autologous stem cell support compared to non-transplant therapy.
The lack of benefit in this study compared to others probably relates to the fact that the non-transplant study arm probably fared better, making HDT appear less beneficial. This related to only randomizing responding patients, employing a very intensive regimen for “standard” therapy, and administering maintenance interferon and dexamethasone. This also may explain a median overall survival of more than 5 years, superior to prior reports. There also appeared to be a slight treatment imbalance in the randomization process with potentially more adverse prognostic factors in the HDT arm. Treatment recommendations become even less clear since a host of novel agents with enhanced activity (eg, bortezomib, thalidomide, and lenalidomide) have become available since accrual was completed in 1999.
Despite these negative results, autologous transplant remains a viable option. To the extent transplant does appear to offer a higher response rate, it may serve as a platform for consolidation with novel agents. However, these data reiterate the importance of steering patients toward a clinical trial, especially if pursuing high-dose therapy with autologous stem cell rescue.
References
1. Attal M, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996;335:91-97.
2. Child JA, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875-1883.
3. Barlogie B, et al. Treatment of multiple myeloma. Blood. 2004;103:20-32.
4. Fermand JP, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998;92:3131-3136.
The results of this study show that HDT intensification, when given to myeloma patients who have responded to the initial chemotherapy, significantly increases the CR rate but has no significant impact on PFS or OS.Subscribe Now for Access
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