Revlimid Maintenance Therapy After Donor Stem Cell Transplantation Is Not Recommended For Multiple Myeloma Patients One Comment By Howard Chang
Published: Aug 19, 2011 11:14 am Results of a recent small Phase 2 study conducted in the Netherlands suggest that Revlimid maintenance therapy improves responses in multiple myeloma patients receiving “mini” donor stem cell transplants. However, the study authors also observed a rapid onset of graft-versus-host disease in these patients after the start of Revlimid treatment.
Based on these findings, the study authors recommended against Revlimid maintenance therapy for myeloma patients receiving “mini” donor stem cell transplants.
“Acute graft-versus-host disease is a life-threatening complication after donor stem cell transplantation, and our primary aim of the article was to warn the myeloma community about this [risk],” the study’s lead author Dr. Monique Minnema of the University Medical Center Utrecht in the Netherlands told the Myeloma Beacon.
“In my view, patients should not be treated with Revlimid maintenance after donor stem cell transplantation outside of clinical trials. If [clinical trials] are to be designed, another strategy has to be followed, like the combination of Revlimid with dexamethasone,” she added.
Donor (allogeneic) stem cell transplantation is the process in which a patient receives high-dose chemotherapy followed by an infusion of stem cells from a matched donor to replace the stem cells destroyed during chemotherapy.
Donor stem cell transplantation may give myeloma patients with advanced disease a better chance for long-term remission than transplantation with their own cells. However, donor stem cell transplantation is also associated with high rates of transplant-related complications, including graft-versus-host disease (GVHD), in which the donor cells attack the recipient’s own cells.
A new strategy known as non-myeloablative (“mini”) donor stem cell transplantation has been shown to decrease the risks associated with traditional donor stem cell transplants by using lower doses of chemotherapy and radiation in preparation for the transplantation.
Past studies have shown that thalidomide (Thalomid) and Velcade (bortezomib) maintenance therapy may improve response in myeloma patients following donor stem cell transplantation without aggravating GVHD.
Two recent studies indicated that Revlimid (lenalidomide) maintenance therapy increases the time to disease progression in myeloma patients following autologous stem cell transplantation (see related Beacon news).
In this study, the Dutch researchers investigated whether Revlimid maintenance is effective in myeloma patients receiving a “mini” donor stem cell transplant.
The study included 30 newly diagnosed myeloma patients with a median age of 53 years.
All patients received three cycles of induction therapy followed by stem cell mobilization with cyclophosphamide, one cycle of high-dose melphalan (Alkeran), and a stem cell transplant with their own cells. All patients also received a “mini” donor stem cell transplant two to six months after receiving the first transplant.
After a median of 12 weeks following the second transplant, they began maintenance therapy with 10 mg Revlimid daily for 21 days in successive 28-day cycles. Patients were scheduled to complete 24 cycles of Revlimid maintenance, but ultimately completed a median of three cycles.
Patients also received medication to suppress the immune system, called immunosuppressive therapy, and to reduce the patients’ risk of developing GVHD. Immunosuppressive therapy was gradually reduced after the first two cycles of Revlimid maintenance in the absence of GVHD.
After a median follow-up of 22 months, 37 percent of patients improved their responses with Revlimid maintenance therapy.
The progression-free survival rate one year from the start of Revlimid maintenance was 69 percent and decreased to 60 percent after two years. The overall survival rate was 93 percent after two years.
According to Dr. Minnema, these results were “not very promising” because they were similar to results of other studies in which patients received a donor stem cell transplant without maintenance therapy.
Eighty-seven percent of patients discontinued Revlimid therapy before completing all 24 cycles, mainly because of GVHD (43 percent), other severe side effects (17 percent), and disease progression (17 percent).
Of the 30 patients included in the study, 53 percent developed GVHD during Revlimid maintenance therapy. Thirty-seven percent developed acute GVHD, which occurs within the first 100 days after the transplant; 30 percent developed acute GVHD within the first two cycles of Revlimid maintenance.
According to the study authors, GVHD frequently develops in patients after they begin receiving reduced doses of immunosuppressive therapy. Patients in the study did not receive reduced doses of immunosuppressive therapy until after the first two cycles of Revlimid maintenance; however, patients frequently developed GVHD soon after starting Revlimid maintenance.
Based on these observations, the study authors attributed the rapid onset of GVHD to the Revlimid therapy itself.
“We think the immune-stimulatory effects of Revlimid are responsible for the induction of GVHD,” explained Dr. Minnema.
For more information, please see the study in the journal Blood (abstract).
Published: Aug 19, 2011 11:14 am Results of a recent small Phase 2 study conducted in the Netherlands suggest that Revlimid maintenance therapy improves responses in multiple myeloma patients receiving “mini” donor stem cell transplants. However, the study authors also observed a rapid onset of graft-versus-host disease in these patients after the start of Revlimid treatment.
Based on these findings, the study authors recommended against Revlimid maintenance therapy for myeloma patients receiving “mini” donor stem cell transplants.
“Acute graft-versus-host disease is a life-threatening complication after donor stem cell transplantation, and our primary aim of the article was to warn the myeloma community about this [risk],” the study’s lead author Dr. Monique Minnema of the University Medical Center Utrecht in the Netherlands told the Myeloma Beacon.
“In my view, patients should not be treated with Revlimid maintenance after donor stem cell transplantation outside of clinical trials. If [clinical trials] are to be designed, another strategy has to be followed, like the combination of Revlimid with dexamethasone,” she added.
Donor (allogeneic) stem cell transplantation is the process in which a patient receives high-dose chemotherapy followed by an infusion of stem cells from a matched donor to replace the stem cells destroyed during chemotherapy.
Donor stem cell transplantation may give myeloma patients with advanced disease a better chance for long-term remission than transplantation with their own cells. However, donor stem cell transplantation is also associated with high rates of transplant-related complications, including graft-versus-host disease (GVHD), in which the donor cells attack the recipient’s own cells.
A new strategy known as non-myeloablative (“mini”) donor stem cell transplantation has been shown to decrease the risks associated with traditional donor stem cell transplants by using lower doses of chemotherapy and radiation in preparation for the transplantation.
Past studies have shown that thalidomide (Thalomid) and Velcade (bortezomib) maintenance therapy may improve response in myeloma patients following donor stem cell transplantation without aggravating GVHD.
Two recent studies indicated that Revlimid (lenalidomide) maintenance therapy increases the time to disease progression in myeloma patients following autologous stem cell transplantation (see related Beacon news).
In this study, the Dutch researchers investigated whether Revlimid maintenance is effective in myeloma patients receiving a “mini” donor stem cell transplant.
The study included 30 newly diagnosed myeloma patients with a median age of 53 years.
All patients received three cycles of induction therapy followed by stem cell mobilization with cyclophosphamide, one cycle of high-dose melphalan (Alkeran), and a stem cell transplant with their own cells. All patients also received a “mini” donor stem cell transplant two to six months after receiving the first transplant.
After a median of 12 weeks following the second transplant, they began maintenance therapy with 10 mg Revlimid daily for 21 days in successive 28-day cycles. Patients were scheduled to complete 24 cycles of Revlimid maintenance, but ultimately completed a median of three cycles.
Patients also received medication to suppress the immune system, called immunosuppressive therapy, and to reduce the patients’ risk of developing GVHD. Immunosuppressive therapy was gradually reduced after the first two cycles of Revlimid maintenance in the absence of GVHD.
After a median follow-up of 22 months, 37 percent of patients improved their responses with Revlimid maintenance therapy.
The progression-free survival rate one year from the start of Revlimid maintenance was 69 percent and decreased to 60 percent after two years. The overall survival rate was 93 percent after two years.
According to Dr. Minnema, these results were “not very promising” because they were similar to results of other studies in which patients received a donor stem cell transplant without maintenance therapy.
Eighty-seven percent of patients discontinued Revlimid therapy before completing all 24 cycles, mainly because of GVHD (43 percent), other severe side effects (17 percent), and disease progression (17 percent).
Of the 30 patients included in the study, 53 percent developed GVHD during Revlimid maintenance therapy. Thirty-seven percent developed acute GVHD, which occurs within the first 100 days after the transplant; 30 percent developed acute GVHD within the first two cycles of Revlimid maintenance.
According to the study authors, GVHD frequently develops in patients after they begin receiving reduced doses of immunosuppressive therapy. Patients in the study did not receive reduced doses of immunosuppressive therapy until after the first two cycles of Revlimid maintenance; however, patients frequently developed GVHD soon after starting Revlimid maintenance.
Based on these observations, the study authors attributed the rapid onset of GVHD to the Revlimid therapy itself.
“We think the immune-stimulatory effects of Revlimid are responsible for the induction of GVHD,” explained Dr. Minnema.
For more information, please see the study in the journal Blood (abstract).