Photo by Chad McNeeley
Tandem autologous/allogeneic hematopoietic stem cell transplant (HSCT) may cure multiple myeloma (MM), according to a phase 2 study.
The study included newly diagnosed patients who received induction therapy followed by an autograft and a non-myeloablative allograft from a matched sibling donor.
The patients have been followed for a median of 8.8 years.
The probability of progression-free survival at 10 years is 41%, and the overall survival is 62%.
The rate of chronic graft-vs-host disease (GVHD) is high, but the rate of non-relapse mortality is low.
“In many hospitals, doctors have abandoned the use of allografts for multiple myeloma due to the risk of toxicity and relapse,” said study author Jean Roy, MD, of the Maisonneuve-Rosemont Hospital and University of Montreal in Quebec, Canada.
“Our results, on the other hand, have led us to offer the treatment to more patients, especially younger patients and those with poorer prognoses.”
Dr Roy and his colleagues reported these results in Bone Marrow Transplantation.
The researchers assessed 92 patients newly diagnosed with MM between 2001 and 2010. Their median age was 52 (range, 39-64), and 97% had Durie–Salmon stage II or III disease.
Patients received an induction regimen consisting of vincristine, doxorubicin, and dexamethasone (2001–2007, n=75) or a bortezomib-based regimen (2008–2010, n=17).
After induction, patients underwent autologous HSCT using melphalan 200 mg/m2.
A median of 4 months later (range, 2-13), after complete clinical recovery, the patients received an allogeneic transplant from a 6/6 HLA-matched sibling donor. Fifty-seven percent of patients had achieved at least a very good partial response before the second transplant.
The allogeneic transplant was performed on an outpatient basis. The graft consisted of G-CSF-mobilized peripheral blood stem cells (target dose ≥ 4×106 CD34+cells/kg).
The conditioning regimen consisted of fludarabine at 30 mg/m2 and cyclophosphamide at 300 mg/m2 for 5 days. GVHD prophylaxis was oral tacrolimus and mycophenolate mofetil.
Results
At a median follow-up of 8.8 years, 56 patients were still alive (and 36 had died).
Forty patients had no evidence of progression, including 11 patients who were still taking systemic immunosuppressive drugs for GVHD. The remaining 16 patients who were still alive had relapsed after allogeneic HSCT.
A total of 45 patients relapsed. Thirty-nine went on to receive treatment with at least 1 new drug (thalidomide, lenalidomide, bortezomib, or pomalidomide).
They received a median of 2 lines of therapy (range, 1–6), and their 5-year overall survival from first relapse was 49%. Ten of these patients were in very good partial response or greater at last follow-up.
Ten patients died from causes other than refractory MM—6 from refractory GVHD, 3 from lung adenocarcinoma (1 smoker), and 1 from invasive aspergillosis.
The cumulative incidence of extensive chronic GVHD was 79%. The cumulative incidence of grade 2-4 acute GVHD at 6 months was 9%. And 3 patients developed grade 3-4 acute GVHD.
Among the 56 patients who were still alive at last follow-up, the probability of being on any systemic immunosuppressive treatment for GVHD is 38% at 5 years and 22% at 10 years.
The probability of overall survival at 10 years is 62%, the probability of progression-free survival is 41%, and the cumulative incidence of non-relapse mortality is 10%.
