Combination chemotherapy before blood stem cell transplant improves progression-free survival

A randomized Phase III clinical trial combining two common chemotherapy agents as a pre-stem cell transplant treatment at The University of Texas MD Anderson Cancer Center demonstrated significantly increased progression-free survival in multiple myeloma patients.

The study, which followed 202 patients, compared busulfan with melphalan versus melphalan alone. Progression-free survival was 65 months for patients receiving combination chemotherapy versus 43 months for patients receiving melphalan alone. Results were reported online at The Lancet Haematology.

“To our knowledge, this study is the first prospective randomized clinical trial reporting the benefit of busulfan plus melphalan as conditioning regimens before autologous stem cell transplantation for multiple myeloma,” said Muzaffar Qazilbash, M.D., professor of Stem Cell Transplantation and Cellular Therapy, the principal investigator and the senior author on the study.

“Our data suggest that busulfan-melphalan conditioning can serve as a useful platform for further improvement of transplant outcomes in myeloma patients,” Qazilbash says.

Chemotherapy conditioning regimens are routinely used before transplantation as a means to eradicate the underlying disease, and to improve the ability for new blood stem cells to rebuild the blood and immune system.  Melphalan and busulfan are alkylating agents that work by damaging DNA in rapidly dividing cells.

The study followed patients ages 70 years or younger with newly diagnosed, stable multiple myeloma. Study participants were randomized between October 2011 and April 2017 in a single-center, open-label trial.

In the trial, 74 percent of patients receiving combination chemotherapy experienced grade 2-3  mucositis, painful inflammation of the mucous membranes in the digestive tract, while only 14 percent of patients who received melphalan alone reported the adverse effect.

A higher incidence of mucositis with busulfan plus melphalan was anticipated due to findings in previous clinical trials. The incidence of grade 3 (severe) mucositis caused by the combination was low at 14%. No patient had grade 4 (life-threatening or disabling) mucositis.

“Despite the higher adverse event burden, busulfan-melphalan together is a superior conditioning regimen,” said Qazilbash. “These results are from a single institution with a large volume of myeloma patients. There is also an ongoing multi-center trial in Spain addressing the same issue. Based on results from these two studies, we are considering a randomized multi-center trial in the U.S. in the near future.”

Median overall survival was not reached in either group. Three-year overall survival was 91% with busulfan plus melphalan versus 89% with melphalan alone. A longer follow up is needed to identify any difference in overall survival.

The study was funded by the National Institutes of Health (CA016672).