ASCO 2016 Abstract #7507: E2408 Phase II Trial – Addition of Bortezomib to Bendamustine-Rituximab Greatly Improves CR Rates in Patients with Untreated High-Risk Follicular Lymphoma
This ASCO 2016 oral abstract presentation took place on Sunday June 5, 9:45am–12:45pm, during the ‘Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia’ session. This session was chaired by Pr Gilles Salles, Head of the Hematology Department in South Lyon hospitals, Lyon, France.
The presentation was given by Dr Andrew M Evens, Director of the Tufts Cancer Center, Chief of the Division of Hematology/Oncology, Director of the Lymphoma Program and Professor at Tufts University School of Medicine, Boston, MA, USA.
This phase IIa, open-label, multicenter study, conducted by the ECOG-ACRIN Cancer Research Group, began in May 2013 and the primary outcome measure was Overall Response Rate (ORR).
ORR for bendamustine-rituximab (BR) plus bortezomib (V) was 91% versus 90% for BR alone. However, BVR demonstrated much higher rates of Complete Remission (CR); 74% for BVR and 58% for BR (2-sided P= 0.016).
Background: Treatment strategies to improve outcomes in HR FL are needed. E2408 tested whether bortezomib (V) improves the CR rate when added to standard BR induction in untreated HR FL and whether lenalidomide (len) improves remission duration when added to maintenance rituximab (MR).
Methods: Eligible pts had untreated HR grade I/II or IIIa FL. HR was defined as high tumor burden by GELF and/or FLIPI 3-5. Pts were randomized to 1 of 3 arms in a 1:2:2 ratio: A) BR x 6 followed by MR x 2 years (yrs) vs B) BVR x 6 (V 1.3 mg/m2 IV/SQ days 1, 4, 8, 11) then MR x 2 yrs vs C) BR x 6 then MR x 2 yrs + len 20 mg/day x 1 yr. Pts enrolled 1/11-5/15. Response was assessed by 2007 IWG criteria using PET/CT. This analysis reports on the first primary objective of CR rate with induction therapy (Tx) with arms A) + C) combined for induction comparison (90% power at 1-sided α of 0.15).
Results: Among 250 randomized HR FL pts, 28 were excluded for not starting Tx (n = 5), ineligibility (n = 8) or central pathology review (n = 15). Analyses are based on 222 pts (BVR n = 85 vs BR n = 137); the arms were well balanced. Among all pts, GELF was high 92%; FLIPI 3-5 55%; ECOG PS 0 = 55%, 1 = 42% and 2 = 3%; marrow involvement 55%; and stages II 7%, III 27% and IV 66%. 86% of all pts received 6 induction cycles without differences between arms. The overall response for BVR was 91% vs 90% for BR, while CR rates were 74% vs 58%, respectively (2-sided P= 0.016). Respective ‘off treatment’ reasons for BVR vs BR were progressive disease in 4% and 7% and toxicity in 6% and 4%. The most common grade 3-4 toxicities (n = 241) for BVR vs BR were neutropenia (35%/30%), sensory neuropathy (SN) (12%/1%), thrombocytopenia (10%/5%), fatigue (6%/7%), febrile neutropenia (3%/5%) and diarrhea (5%/1%); 91% of grade 3 SN occurred with IV bortezomib (grade 3 SN incidence: 14% IV vs 4% SQ, OR = 3.7, P= 0.2). During induction Tx, there were 3 deaths (2 due to disease), all on arm C.
Conclusions: This initial report of E2408 for untreated HR FL shows that the CR rate for BVR induction Tx was significantly superior compared with BR. Continued follow up is needed to assess survival and if len added to MR improves outcomes. Clinical trial information: NCT01685008.
Evens AM, et al. Effect of bortezomib on complete remission (CR) rate when added to bendamustine-rituximab (BR) in previously untreated high-risk (HR) follicular lymphoma (FL): a randomized phase II trial of the ECOG-ACRIN Cancer Research Group (E2408). J Clin Oncol 34, 2016 (suppl; abstr 7507).