Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities

Desikan, Raman; Barlogie, Bart; Sawyer, Jeffrey R.; Ayers, Dan; Tricot, Guido; Badros, Ashraf; Zangari, Maurizio; Munshi, Nikhil C.; Anaissie, Elias; Spoon, D.; Siegel, David S.; Jagannath, Sundar; Vesole, David H.; Epstein, Joshua; Shaughnessy, John D.; Fassas, Athanasios; Lim, Seah H.; Roberson, Paula K.; Crowley, John

doi:10.1182/blood.v95.12.4008

Cited by 280 publications

(74 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results presented here support the notion that doseintensified MEL, to the level of bone marrow aplasia requiring haematopoietic cellular support, can accomplish 10-and 15-year survival rates in a substantial proportion of patients, one-half of whom have not yet relapsed, including one-fifth (17%) of the initial 41% who are enjoying continuous complete remission. Both the original publication of TT1 data (Barlogie et al, 1997) and the current long-term update support the existence of myeloma sub-entities best captured by cytogenetics, historically (Tricot et al, 1995;Desikan et al, 2000), and now even better by molecular genetics (Avet-Loiseau et al, 2002;Zhan et al, 2002). Although CA was associated with inferior outcome overall, a fraction of such patients enjoyed prolonged survival.…”

Section: Discussionmentioning

confidence: 91%

Long‐term outcome results of the first tandem autotransplant trial for multiple myeloma

et al. 2006

Self Cite

View full text Add to dashboard Cite

Summary Total Therapy 1, the first tandem autotransplant trial for newly diagnosed patients with multiple myeloma, was designed to increase the frequency of complete response (CR) and thereby extend survival. With a median follow‐up of 12 years, 62 of 231 initially enrolled patients are alive (17% at 15 years); 31 remain event free (7% at 15 years) including 16 of 94 (41%) that initially achieved CR. Currently alive patients less frequently had cytogenetic abnormalities (CAs) at baseline (P = 0·002), postenrolment (P < 0·001) and at relapse (P = 0·004); elevations of serum C‐reactive protein (CRP) (P = 0·003) and lactate dehydrogenase (P = 0·029), anaemia (P = 0·029) and they more often completed two transplants within 12 months (P = 0·019). Postenrolment overall survival (OS) and event‐free survival (EFS) were superior in the absence of CA of the hypodiploidy or deletion 13 variety (P < 0·001 and 0·037 respectively) and in the presence of low CRP at baseline (P = 0·001 and 0·017 respectively). Postrelapse survival was longer in the absence of CA at relapse (P < 0·001), IgA isotype (P = 0·002), International Staging System stage 3 (P = 0·014), and when patients had two protocol transplants prior to relapse (P = 0·038). Ten‐year EFS and OS could be accomplished in 15% and 33% of patients, respectively, when all agents available in 1989, especially high‐dose melphalan, were applied together upfront for the management of myeloma.

show abstract

Section: Discussionmentioning

confidence: 91%

Long‐term outcome results of the first tandem autotransplant trial for multiple myeloma

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…The Arkansas group has reported improved complete remissions with tandem transplant with the best results observed in patients with less than 12 months of prior therapy who received tandem transplants within 6 months. 13,17,45 The French Myeloma Intergroup has completed a randomized trial comparing single with tandem transplant.The final analysis of this trial is not yet completed. The preliminary results show no difference in overall survival between groups at a median follow-up of 4 years.…”

Section: Autologous Transplantsmentioning

confidence: 99%

“…50 Unfortunately, even with tandem transplants, there does not appear to be a plateau in post-transplant survival curves indicating that cures are unlikely with this approach. 17,[43][44][45][46][47][48][38][39][40][41][42][43] Novel new approaches are imperative to improve outcomes.…”

Section: Autologous Transplantsmentioning

confidence: 99%

Multiple Myeloma: An Old Disease with New Hope for the Future

Zaidi

2001

CA: A Cancer Journal for Clinicians

View full text Add to dashboard Cite

Multiple myeloma is a currently incurable malignancy of terminally differentiated plasma cells. It typically occurs in older patients (median age 71 years). Clinical manifestations result from monoclonal protein (immunoglobulin) production and its accumulation in the serum and/or urine, anemia, lytic bone disease, hypercalcemia, renal insufficiency, and immune deficiency. Myeloma cells have low proliferative activity—most myeloma experts opine that the initial oncogenic event occurs 10‐15 years before clinical disease manifestation. In addition, myeloma cells develop multiple chromosomal abnormalities, which may explain the native resistance of myeloma patients to conventional therapy and our inability to completely eradicate the disease. Indeed, with conventional therapy, only 5% of patients achieve complete response. Minimal improvement has been observed with conventional therapies over the past 20‐30 years; the median duration of initial response remains approximately 18 months with median survival in the 36‐month range. However, recent clinical trials have established high‐dose therapy with autologous hematopoietic stem cell transplant as superior to conventional therapy: complete remission rates of 25‐30% can be affected with median survival exceeding 5 years. Newer approaches to improve treatment outcomes are in active clinical trials including: more potent induction regimens utilizing thalidomide, alone or in combination with dexamethasone; tandem transplants to improve complete remission rates; newer approaches to maintenance therapy using thalidomide with corticosteroids; non‐myeloablative therapy with allogeneic transplant; and post‐transplant vaccinations.

show abstract

“…CR is achieved in 5-10% of the patients with conventional chemotherapy (1,8). CR with a single course of HDT is reported in the 22-35% range and in range of 30-45% following tandem ASCT (8,(12)(13)(14)(15)(16)(17). Several trials combined the two transplantation modalities to increase CR rate (18)(19)(20): ASCT to cause maximal tumor cytoreduction and NST to eradicate minimal residual disease via the GVM effect.…”

mentioning

confidence: 99%

High complete remission rate and durable remissions achieved with rational use of autologous stem‐cell transplantation, thalidomide maintenance, and non‐myeloablative allogeneic transplantation in patients with multiple myeloma

Oyan

Koç

Özdemir

et al. 2009

Clinical Transplantation

View full text Add to dashboard Cite

Autologous stem-cell transplantation (ASCT) has emerged as the standard approach in patients with multiple myeloma, although it is unlikely to achieve cure. Thalidomide maintenance and non-myeloablative allogeneic transplantation (NST) may increase complete remission (CR) rate and increase overall survival. In this study, 35 ASCT and 10 NST were performed in 33 patients. Patients, who were resistant or relapsed following ASCT, underwent NST if they had an HLA-matched sibling, otherwise treated with a second ASCT. Thalidomide was started as maintenance after ASCT. After first transplantation, three patients underwent second ASCT and 10 patients underwent NST. Following first transplantation, CR rate was 39% and increased to 60% (overall response 93%) with addition of thalidomide, bortezomib, and second transplantation. CR was durable in 14 (42%) patients. During a median follow-up of 24 months, 18 patients progressed and nine patients died. The 100-d transplant-related mortality was <5%. The four-yr progression-free survival (PFS) was 52.4%. In conclusion, ASCT followed by thalidomide and NST in resistant patients can lead to high CR and PFS rates. As a second transplantation has not been performed routinely, patients having durable CR had a chance to avoid or delay a second transplantation without compromising disease control.

show abstract

Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities

Cited by 280 publications

References 15 publications

Long‐term outcome results of the first tandem autotransplant trial for multiple myeloma

Long‐term outcome results of the first tandem autotransplant trial for multiple myeloma

Multiple Myeloma: An Old Disease with New Hope for the Future

High complete remission rate and durable remissions achieved with rational use of autologous stem‐cell transplantation, thalidomide maintenance, and non‐myeloablative allogeneic transplantation in patients with multiple myeloma

Contact Info

Product

Resources

About