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Autologous, nonmyeloablative HSCT show promise for advanced multiple myeloma
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A frontline transplant tandem approach consisting of autologous and nonmyeloablative allogeneic transplantation demonstrated promising OS and PFS among patients with multiple myeloma, according to phase 2 study results.
Although new drug therapies and autologous hematopoietic stem cell transplantation have improved outcomes for multiple myeloma, the condition remains largely incurable, according to study background.
“Allogeneic HSCT represents a potential curative option for multiple myeloma patients,” Jean Roy, MD, associate professor of medicine at University of Montreal and department head of hematology and oncology at Maisonneuve-Rosemont Hospital, and colleagues wrote. “Early studies using myeloablative regimens in patients with advanced disease have reported a PFS range from 34% to 70% at 4 years to 6 years in those achieving complete remission after allogeneic transplant. Factors associated with improved PFS included fewer treatments before transplant, grade I acute graft-versus-host disease [GVHD] and presence of chronic GVHD.”
However, myeloablative HSCT appeared associated with a higher incidence of nonrelapse mortality, according to the researchers.
Thus, to maximize the anti-myeloma effect and minimize nonrelapse mortality, Roy and colleagues developed a nonmyeloablative regimen associated with a high incidence of chronic GVHD.
The analysis included data from 92 newly diagnosed patients (median age, 52 years; range, 39-64; 57% men) treated between 2001 and 2010. Each patient underwent autologous HSCT. Sixty to 100 days later, the patients underwent an outpatient nonmyeloablative allogeneic HSCT from a 6/6 HLA-matched sibling donor with fludarabine and cyclophosphamide conditioning.
Median follow-up was 8.8 years.
The researchers observed classical acute GVHD in 9% of patients (95% CI, 4-17).
Patients treated with the combined autologous and nonmyeloablative regimens experienced a 10-year PFS probability of 41% (95% CI, 30-52; median, 4.3 years). The 10-year OS probability was 62% (95% CI, 51-72; median not reached).
Despite a high cumulative incidence of chronic GVHD (79%), the majority of long-term survivors discontinued immunosuppressive drugs by 5 years after treatment. Among survivors, the probability of being on any systemic immunosuppressive treatment at 5 years was 38% (95% CI, 27-49); by 10 years, it was 22% (95% CI, 7-39).
The 10-year incidence of nonrelapse mortality was 10% (95% CI, 4-18).
Ten patients died of causes other than multiple myeloma, including refractory GVHD (n = 6), lung cancer (n = 3, including one smoker) and invasive aspergillosis (n = 1).
“In many hospitals, doctors have abandoned the use of allografts for multiple myeloma due to the risk for toxicity and relapse,” Roy said in a press release. “Our results, on the other hand, have led us to offer the treatment to more patients, especially younger patients and those with poorer prognoses.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
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