A recent paper published in the Journal of Clinical Oncology updated the outcomes of multiple myeloma trials conducted by the Intergroupe Francophone du Myelome, the Southwest Oncology Group, and the University of Arkansas for Medical Sciences.

The update provides a fuller, long-term picture of the advantages of some of the autotransplant regimens being tested. It represents the first international effort at systematically updating previously reported trial results, which had indicated that autotransplantation with high-dose melphalan (Alkeran) therapy significantly extends the survival of multiple myeloma patients.

Autologous stem cell transplantation, or autotransplantation, is a common treatment option for newly diagnosed myeloma patients. Stem cells are collected from the patient before chemotherapy and then transplanted afterward to replace the stem cells destroyed during the chemotherapy treatment.

“Given the fortunately extended survival now enjoyed by many myeloma patients, it is critical to provide long-term follow-up analyses as done in this paper,” said Dr. Bart Barlogie, lead author of the paper.

The report updated the results for eight autotransplantation trials. The trials are summarized in the table below:

Following up on these studies resulted in several important observations.

Increased survival in newer trials. The 10-year overall survival estimates increased in more recent trials, from 20 percent to 30 percent in IFM90, IFM94, S9321, and TT1.

New longer-term information on thalidomide use. Although the original results from IFM9902 noted a survival benefit with thalidomide maintenance therapy, the longer follow-up could not confirm these findings. Dr. Barlogie said that it is currently not fully understood why the initial observations, though statistically significant, did not hold up over time.

However, this long-term follow-up study uncovered that patients who received TT2 experienced significant survival improvement with thalidomide induction therapy, though this was noted almost eight years after the trial and after 80 percent of patients had discontinued its use. It is not yet known why the survival benefit of thalidomide in TT2 was not observed for so long, but this delay has also been observed with high-dose glucocorticoid therapy in an acute form of pediatric lymphoblastic leukemia.

Dr. Barlogie, who leads the research group that conducted the original TT2 trial, speculated that thalidomide may be particularly effective at the start of therapy, resulting in a survival benefit. In order to compare the efficacy of the thalidomide-based treatment versus the control, Dr. Barlogie’s group plans on examining bone marrow samples from patients in both treatment groups obtained periodically over the first year of treatment.

Better survival rates for some trials over others. Researchers also analyzed the eight trials using four variables that independently affect overall survival: albumin, B2M, LDH, and hemoglobin levels. They observed superior survival rates for the TT2, TT3, and IFM9902 trials, compared to the other five trials; for tandem transplantations, compared to both single transplantations and standard therapies; and for tandem transplantations with thalidomide, compared to trials without thalidomide.

The authors of the study concluded that longer follow-up is needed in order to fully appreciate the collective impact of successful therapeutic interventions. Although the current paper only updated the results of three research groups, the authors encourage other groups to follow their lead.

In order to have a complete understanding of the survival effects of therapeutic trials, Dr. Barlogie recommended that clinical trial participants be followed for the rest of their lives.

For more information, please see the study in the Journal of Clinical Oncology (abstract).