Reduced-intensity allogeneic transplant effective salvage therapy in follicular lymphoma

Patients with follicular lymphoma who experienced disease recurrence after autologous stem cell transplant demonstrated benefit from reduced-intensity allogeneic transplant salvage therapy, according to retrospective results.

Between 70% and 80% of patients with follicular lymphoma relapse after autologous hematopoietic stem cell transplantation (HSCT), many of whom will die of their disease. The optimal salvage therapy for patients who experience relapse has not been established.

Although it has been suggested that reduced-intensity allogeneic HSCT may overcome the poor prognostic impact of early relapse after initial autologous HSCT, there are little data describing the outcomes of patients who undergo this regimen.

Stephen P. Robinson, PhD , of the bone marrow transplant unit at University Hospital Bristol NHS Foundation Trust, United Kingdom, and colleagues evaluated data from 183 patients (median age, 45 years; range, 21-69) who underwent reduced-intensity allogeneic HSCT as salvage therapy a median of 30 months after autologous HSCT. Prior to allogeneic HSCT, patients had received a median of four lines (range, 3-10) of therapy.

Sixteen percent of patients had chemotherapy-resistant disease, whereas 81% had chemotherapy-sensitive disease.

Siblings (47%) and unrelated donors (53%) provided grafts for reduced-intensity allogeneic HSCT.

Median follow-up after reduced-intensity allogeneic HSCT was 58.8 months (range, 3-159).

Overall, 171 patients (93%) engrafted, nine patients (5%) did not engraft and two patients experienced secondary graft failure.

Eighty patients developed acute graft-versus-host disease (GVHD), 26% was grade I and 27.9% was grade II to grade IV. Ninety-three patients developed chronic GVHD and the 2-year cumulative incidence of chronic GVHD was 51.2%.

Nonrelapse death occurred in 51 patients as a result of infection (n = 13), GVHD (n = 10), infection and GVHD (n = 11), GVHD and multiorgan failure (n = 6) or other causes (n = 11).

The cumulative incidence of nonrelapse mortality was 11.9% at 100 days and 27.4% at 2 years.

Twenty-six patients experienced relapse or disease progression a median of 5.6 months (range, 1-90) after reduced-intensity allogeneic HSCT. The estimated cumulative incidence of relapse at 5 years was 16%.

Age older than 45 years increased risk for nonrelapse mortality (RR = 2.1; 95% CI, 1.2-3.6) and disease relapse (RR = 2; 95% CI, 1.2-3.5), whereas having chemotherapy-sensitive disease reduced risk for nonrelapse mortality (RR = 0.5; 95% CI, 0.2-1) and disease relapse (RR = 0.2; 95% CI, 0.1-0.5). Donor source did not appear associated with risks for nonrelapse mortality or disease relapse.

Among 122 patients who engrafted and did not die of nonrelapse mortality or a secondary malignancy, the median remission following reduced-intensity allogeneic HSCT was 43 months (range, 1-156), whereas the median remission following initial autologous HSCT was 14 months (range, 1-204).

Rates of PFS were 61.8% at 2 years and 47.7% at 5 years. Overall, 63.3% of patients achieved 2-year OS and 51.1% achieved 5-year OS.

Again, results of a multivariate analysis indicated age older than 45 years and chemotherapy refractoriness at reduced-intensity allogeneic transplant were the only factors associated with poorer PFS and OS.

“Of note, the disease control achieved in this high-risk group of patients was impressive with only 15.7% of patients experiencing a relapse after prolonged follow-up,” the researchers wrote. “The latest relapse event in this cohort occurred at 90 months with the majority of relapses occurring within the first year of the transplant. Later relapses may yet occur with longer follow-up, but the plateaus observed in the relapse curve in this and other studies of transplant are suggestive that these procedures are a curative treatment for patients with multiply relapsed follicular lymphoma.” – by Jennifer Southall

Disclosure: The researchers report no relevant financial disclosures.