Addition of Rituximab to Salvage Chemotherapy in Aggressive CD20+ Lymphoma Prior to Autologous Stem Cell Transplant (ASCT): A Cohort Comparison from the NCIC CTG Study LY.12
Authors: Baetz Tara , Chen Bingshu E , Couban Stephen , Kouroukis C. Tom , Buckstein Rena , Kuruvilla John , Howson-Jan Kang , Szwajcer David , Federico Massimo , Meyer Ralph M. , Turner Robert , Djurfeldt Marina S , Hay Annette E , Shepherd Lois , Crump Michael 
Published: October 2019

Background: The addition of rituximab (R) to salvage chemotherapy has been shown to improve response rates and proportion of patients subsequently transplanted with Aggressive CD 20+ Non-Hodgkin Lymphoma who were previously R naïve. It is unknown if this benefit would be seen in the era of patients requiring ASCT who had previously been treated with R + chemotherapy.

Methods: The NCIC CTG study LY.12 is a phase III study that evaluated gemcitabine, dexamethasone and cisplatin (GDP) as a salvage regimen compared with dexamethasone, cytarabine, cisplatin (DHAP), and demonstrated that GDP was non-inferior with respect to response rate and showed similar results for rates of transplantation and event-free survival (Crump et al, ASH 2012; in press JCO 2014). In addition GDP resulted in less toxicity and was highly cost effective compared to DHAP. Between Aug 2003 and Oct 2011, 619 patients (pts) were accrued; 414 had CD 20+ lymphoma and received R with their initial treatment. Ninety six pts were accrued between 2003-05 and received GDP or DHAP without R; following a protocol amendment in 2005, 318 pts received R on day 1 of each cycle of salvage chemotherapy. We compared these two cohorts to determine whether there is a benefit to adding R to DHAP or GDP in those pts who have relapsed or are refractory (stable disease or progressive disease) after R containing first-line treatment. Response assessment by CT scan was performed following two cycles of salvage treatment. Subsequent mobilization, choice of high-dose chemotherapy regimen and use of post-transplant radiation were at investigator discretion.

Results: Of the 414 pts in this analysis, median age was 55.7 years (range 18-71); 78% had diffuse large B cell lymphoma and 14.5% transformed from indolent lymphoma; 35% were refractory to first line treatment and 46.9% had relapsed within 1 year; 34.5% had IPI score 3 or higher at study enrolment. 41.3% of pt had an elevated LDH and 33.1% had B symptoms prior to salvage therapy. Most had no prior radiation treatment (78.7%).

Equal number of pts in the R+ and R- groups received DHAP as GDP as salvage chemotherapy. The R- group was slightly younger (53.7 vs 56 years, P=0.03), had a higher ECOG Performance status >1 (19.8% vs 11.6%, P=0.041) and a higher proportion of pts relapsing within 1 year of R-CHOP (59.4% vs 43.1%, P=0.002).

The rate of CR/Cru (15.7% vs 4.2%, p = 0.0032) and overall RR (45.6% vs 25%, P=0.0003) were significantly better in the R+ group. The transplantation rate was significantly greater in the R+ group 165/318 versus the R- group 30/96 (51.9% vs. 31.3%; P=0.0004). Multivariate analysis revealed that response rate was significantly higher in those receiving R with salvage, longer remission after primary therapy and without B symptoms at relapse. We were unable to detect differences in EFS and OS between the groups who received or did not receive R (4 year EFS 22 vs. 20%, HR = 0.85, P=0.26; 4 year OS 35 vs 31%, HR = 0.83, P=0.18).

Conclusion: Although this is a retrospective analysis, these data suggest that in patients with relapsed/refractory CD20+ aggressive lymphoma, the addition of rituximab to subsequent salvage treatment improves RR and the proportion of patients proceeding to ASCT. Additional strategies are required to improve outcomes post-ASCT.

Disclosures

Baetz: Roche: Consultancy; Lundbeck: Consultancy; Bristol-Myers Squibb: Consultancy. Meyer:Celgene: Honoraria.