Rituximab confers EFS benefit in B-lineage ALL

The addition of rituximab to standard chemotherapy improved EFS in adult patients with CD20–positive, Philadelphia chromosome–negative B-lineage acute lymphoblastic leukemia, according to randomized study results published in The New England Journal of Medicine.

However, the improvement in EFS did not translate into significantly improved OS, results showed.

“The outcome for adults with ALL has significantly improved over the past decade, notably because of treatment with more intensive chemotherapy, similar to that used for pediatric ALL, and risk-adapted use of allogeneic hematopoietic stem cell transplantation,” Hervé Dombret, MD, director of clinical research in hematology and head of the adult clinical hematology unit at Paris Diderot University, and colleagues wrote. “Biologic features of some ALL subtypes have also offered opportunities for targeted treatments.”

Rituximab (Rituxan; Genentech, Biogen) — which targets the CD20 antigen — has improved outcomes among patients with B-cell non-Hodgkin lymphoma and Burkitt’s leukemia and lymphoma. Prior single-arm studies have suggested it might hold a benefit for patients with B-lineage ALL, which also may have the CD20 antigen.

Dombret and colleagues evaluated whether the addition of rituximab to standard chemotherapy led to better EFS outcomes in patients with CD20–positive, Philadelphia chromosome (Ph)–negative ALL in a randomized trial.

The study included data from 209 patients (median age, 40.2 years; interquartile range, 24.5-52.6), whom the researchers randomly assigned to chemotherapy with (n = 105) or without (n = 104) 375 mg/m² IV rituximab.

EFS served as the primary endpoint. Secondary outcome measures included rate of hematologic remission, cumulative incidences of relapse and death during first remission, OS and safety.

After a median follow-up of 30 months, 101 patients (rituximab, n = 44; control, n = 57) had experienced at least one event. Seventeen patients (rituximab, n = 8; control, n = 9) experienced induction failure, and 57 patients (rituximab, n = 22; control, n = 35) relapsed. Twenty-seven patients (rituximab, n = 14; control, n = 13) died in remission.

Two patients — both in the rituximab group — were lost to follow-up during the first 12 months.

EFS significantly favored patients assigned rituximab (HR = 0.66; 95% CI, 0.45-0.98). The researchers estimated a 2-year EFS of 65% (95% CI, 56-75) among patients assigned rituximab, compared with 52% (95% CI, 43-63) among patients in the control group.

The researchers attributed the EFS difference to the lower number of relapses seen among patients assigned rituximab (subdistribution HR = 0.52; 95% CI, 0.31-0.89).

The prolonged EFS associated with rituximab did not correspond with a significant OS benefit (HR = 0.7; 95% CI, 0.46-1.07).

A total of 246 serious adverse events occurred, with similar rates in both groups (rituximab, n = 128; control, n = 118). More patients assigned rituximab experienced infections (71 vs. 55), and significantly more experienced allergic reactions (14 vs. 2; P = .002).

“Our study has several limitations related to the multiple comparisons required for prespecified secondary endpoints and post-hoc analyses,” Dombret and colleagues wrote. “Despite these limitations, the results provide evidence of a beneficial effect of the addition of rituximab to chemotherapy in adults with CD20–positive, Ph–negative B-cell precursor ALL. Other surface antigens, such as CD19 or CD22, which ALL blasts express more frequently than they express CD20, may also be targeted by various antibodies or chimeric antigen receptor T cells that have already shown efficacy in patients with relapsed or refractory ALL.” – by Cameron Kelsall

Disclosures: Dombret reports grant support from the French Ministry of Health and nonfinancial support from Roche during the conduct of the study, as well as grant support and personal fees from Genentech/Roche and multiple other pharmaceutical companies outside the submitted work. Please see the full study for a list of all other researchers’ relevant financial disclosures.