Phase 2 Trial of Interim PET Scan-Tailored Therapy in Patients with Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL) in British Columbia (BC)

Abstract

Introduction: While the majority of patients (pts) with advanced stage DLBCL will be cured with R-CHOP, pts who fail front-line therapy continue to have a dismal outcome. Optimization of initial therapy remains an important goal. Interim PET scanning has been demonstrated to be prognostic in DLBCL and may be a promising tool to select pts in whom alternate non-cross-resistant therapies should be considered prior to the emergence of further drug resistance. With this rationale, a phase 2 trial was initiated to assess the feasibility and efficacy of PET-tailored therapy for DLBCL within the province of BC. Methods: This phase II trial was conducted at multiple sites within the BC Cancer Agency. Patients >17 years of age with biopsy proven de novo advanced stage DLBCL, including PMBCL (stages 3 and 4, or stages 1 and 2 with B-symptoms or bulky mass > or = 10cm), with an ECOG PS Results: 155 patients were enrolled between Oct 2006 and May 2014. Patient characteristics: median age 53 y (range 19-79); 54% male; 105 (68%) stages 3 or 4; 52 (34%) age >60 y; 55 (35%) ECOG PS >1; 90 (60%) elevated LDH; 44 (28%) extranodal sites >1; 81 (52%) bulky mass ³10cm; and 65 (42%) IPI score 3-5. 2 patients were non-evaluable: no interim PET due to toxicity (n=1), withdrawal (n=1). 3 pts were taken off study due to progression on R-CHOP. Of the 150 evaluable pts with interim PET, 88 (59%) were PET-neg, 50 (33%) were PET-pos and 12 (8%) were PET-ind. PET-pos pts were more likely to have elevated LDH and bulky disease at diagnosis. All PET-neg pts completed treatment with R-CHOP as intended and none received XRT. Of the 50 PET-pos pts, 2 refused to switch to R-ICE and completed treatment with R-CHOP (both received XRT). 48/50 PET-pos pts proceeded to R-ICE: 9 pts failed to complete all 4 cycles R-ICE due to toxicity and 6/9 switched back to R-CHOP; 3 progressed during R-ICE and did not have a final PET scan. The remaining 36/50 PET-pos pts completed 4 cycles R-ICE and underwent a final PET: 11/36 had a negative PET post R-ICE (2 received XRT, regardless); 25/36 had a positive PET post R-ICE (12 received XRT). Of the 12 PET-ind pts, 10 completed treatment with R-CHOP (1 with XRT), while 2 were switched to R-ICE (no XRT). With a median follow-up time of 45 mos, 4-y PFS and overall survival (OS) for the evaluable cohort were 79% and 87%, respectively. PET-neg pts had a very favorable outcome (4-y PFS 91%, 4-y OS 96%), whereas PET-pos pts had a less favorable outcome (4-y PFS 59%, 4-y OS 73%). PET-ind pts had an intermediate outcome with 4-y PFS 83% and 4-y OS 82%. Conclusions: While PET-tailored therapy in pts with advanced stage DLBCL was feasible in BC, approximately 20% of patients were unable to tolerate the planned 4 cycles of R-ICE due to various toxicities, mainly myelosuppression. Pts who were PET-neg following 4 cycles of R-CHOP had an excellent outcome, without need for XRT. PET-pos pts had a poorer outcome, but did better than expected compared to historical reports. However, relatively few PET-pos pts converted to a negative PET scan following R-ICE, suggesting that simply switching to this alternate non-cross resistant chemotherapy regimen is insufficient to overcome the inherent resistance in this poor risk population. Disclosures Sehn:Roche/Genentech: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Off Label Use: Use of R-ICE chemotherapy in front-line therapy of DLBCL.. Hardy:Roche Canada: Research Funding. Gill:Roche Canada: Research Funding. Al-Tourah:Roche Canada: Research Funding. Shustik:Roche Canada: Research Funding. Macpherson:Roche Canada: Research Funding. Yee:Roche Canada: Research Funding. Lam:Roche Canada: Research Funding. Savage:Roche Canada: Research Funding. Klasa:Roche Canada: Research Funding. Villa:Roche Canada: Research Funding. Gerrie:Roche Canada: Research Funding. Shenkier:Roche Canada: Research Funding. Slack:Roche Canada: Research Funding. Gascoyne:Roche Canada: Research Funding. Benard:Roche Canada: Research Funding. Wilson:Roche Canada: Research Funding. Tonseth:Roche Canada: Research Funding. Connors:Roche Canada: Research Funding.