DLBCL

ASCO 2016 Abstract #7506: No Improved DFS, But Improved OS and LSS, Observed with Adjuvant Everolimus Therapy Versus Placebo for Poor-Risk DLBCL

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 abstract was presented by Dr Thomas E Witzig of the Mayo Clinic Cancer Center in Rochester, MN.

PILLAR2 is a randomized, double-blind, multicenter, phase III study investigating everolimus (EVE) adjuvant therapy versus placebo (PBO) in patients with poor-risk Diffuse Large B-Cell Lymphoma (DLBCL) who have achieved a complete response with first-line rituximab-chemotherapy. The primary outcome measure of PILLAR2 was Disease Free Survival (DFS). The secondary outcome measures were Overall Survival (OS), Lymphoma-Specific Survival (LSS) and a comparison of the safety profiles of EVE versus PBO. LSS is the time from randomization to death caused by lymphoma. 741 patients enrolled on the trial which began in July 2009.

Adjuvant EVE for 1 year did not improve DFS when compared to PBO; the two year DFS rates were 78% (73-82%) and 77% (72-81%) in the adjuvant EVE and PBO arms, respectively. However, improved OS and LSS were observed with adjuvant EVE compared with PBO. The authors conclude that additional exploration into adjuvant EVE therapy for high-risk DLBCL should be undertaken.

Abstract 7506

Background: The goal of PILLAR-2 (NCT00790036) was to reduce DLBCL relapse by providing 1 year of adjuvant EVE to poor-risk (International Prognostic Index [IPI] ≥3) pts who had achieved a CR with R-chemo.

Methods: PILLAR-2 was a multicenter double-blind, placebo (PBO)-controlled, phase 3 study. Pts with histologically confirmed stage III/IV poor-risk (IPI ≥3) DLBLC who had a PET/CT-confirmed CR to first-line R-chemo were randomized 1:1 to EVE 10 mg/day or PBO for 1 year or until disease relapse, unacceptable toxicity, or death. The primary endpoint was disease-free survival (DFS) by local assessment using revised IWRC; secondary endpoints were overall survival (OS), lymphoma-specific survival (LSS), and safety.

Results: Median study follow-up was 50.4 months (range, 24.0–76.9 months). Of the 742 pts randomized, 177 (48%) pts in the EVE and 249 (67%) in the PBO arms completed the study treatment as per protocol. Overall, 47% pts were ≥65 years, 50% were male and 42% had an IPI of 4+5. Adjuvant EVE did not improve DFS vs. PBO (Log-rank p = 0.276) (Table). The 2-yr DFS rates (95% CI) were 78% (73-82%) in EVE vs 77% (72-81%) in PBO. However, trends favoring EVE were observed for OS and LSS, and for exploratory analyses of DFS and OS in males and those with IPI 4+5. Common grade 3/4 AEs with > 3% difference for EVE vs PBO included neutropenia, stomatitis, CD4 lymphocytes decreased, lymphopenia and anemia.

Conclusions: In poor-risk DLBCL patients with a CR after R-chemo, adjuvant EVE for 1 year did not improve DFS. A trend favoring EVE for OS and LSS, overall and for DFS in selected patient subgroups suggests that everolimus may provide anti-lymphoma activity in high-risk DLBCL, and warrant further investigation. Clinical trial information: NCT00790036.

 

EVE vs PBO
Hazard ratio (95% confidence interval)

DFS*

 

Overall (n = 742)

0.92 (0.69–1.22)

IPI 4+5 (n = 313)

0.65 (0.42–1.01)

Male (n = 372)

0.68 (0.45–1.05)

OS*

 

Overall (n = 742)

0.75 (0.51–1.10)

IPI 4+5 (n = 313)

0.63 (0.37–1.07)

Male (n = 372)

0.55 (0.32–0.94)

LSS* (n = 742)

0.64 (0.39–1.04)

Reference

Witzig TE, et al. PILLAR-2: a randomized, double-blind, placebo-controlled, phase III study of adjuvant everolimus (EVE) in patients (pts) with poor-risk diffuse large B-cell lymphoma (DLBCL). J Clin Oncol 34, 2016 (suppl; abstr 7506).