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Clinical Trial
. 2016 Oct;122(19):2996-3004.
doi: 10.1002/cncr.30137. Epub 2016 Jun 28.

Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496)

Stefan K Barta  1 , Hailun Li  2 , Howard S Hochster  3 , Fangxin Hong  2 , Edie Weller  2 , Randy D Gascoyne  4 , Thomas M Habermann  5 , Leo I Gordon  6 , Natalia Colocci  7 , Elizabeth M Bengtson  8 , Sandra J Horning  9 , Brad S Kahl  10
Affiliations
Clinical Trial

Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496)

Stefan K Barta et al. Cancer. 2016 Oct.

Abstract

Background: In an ECOG-ACRIN Cancer Research Group study (E1496), maintenance rituximab (MR) was reported to prolong progression-free survival (PFS) in comparison with observation (OBS) alone in patients with indolent lymphoma after induction chemotherapy. Here the long-term follow-up of the same patient cohort is presented.

Methods: Patients with indolent lymphoma received induction chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). Patients with stable disease or a better response were then randomized to weekly rituximab (375 mg/m(2) × 4 doses) every 6 months for 2 years (MR) or to OBS. The primary endpoint was PFS; the secondary endpoints were overall survival (OS), response rate, and toxicities.

Results: Of the 387 patients who initially received CVP induction, 158 were randomized to MR, and 153 were randomized to OBS. After a median follow-up of 11.5 years, patients on MR had longer median PFS (4.8 years) than patients on OBS (1.3 years; hazard ratio [HR], 0.49; P < .0001). However, there was no difference in OS between MR and OBS (10-year OS, 67% vs 59%; median OS, 13.5 years vs not reached; HR, 0.91; P = .69). Other than MR, only minimal residual disease after induction therapy was significantly associated with PFS on multivariate analysis (HR, 0.71; P = .02). A low initial tumor burden, minimal residual disease, follicular histology, a low Follicular Lymphoma International Prognostic Index score, and female sex were associated with longer OS. There was no increase in the rate of second primary malignancies with MR vs OBS.

Conclusions: With long-term follow-up, MR did not influence OS. The PFS benefit was maintained. MR should be considered optional for patients with indolent B-cell lymphoma. Cancer 2016;122:2996-3004. © 2016 American Cancer Society.

Keywords: follicular lymphoma; indolent lymphoma; non-Hodgkin lymphoma; rituximab; rituximab maintenance.

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Conflict of interest statement

disclosures: S.H. is an employee of Genentech; the authors report no other relevant conflicts of interests

Figures

Figure 1
Figure 1
Consort diagram for E1496
Figure 2
Figure 2
Progression-free survival for a) all evaluable patients (n=311) and b) patients with follicular lymphoma (n=228)
Figure 3
Figure 3
Overall survival for a) all evaluable patients (n=311) and b) patients with follicular histology (n=228)
See this image and copyright information in PMC

References

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