LBA7005 Background: Despite recent advances, there remains a need for novel therapies for pts with R/R DLBCL. BV, an anti-CD30 antibody-drug conjugate, has shown efficacy and safety when combined with lenalidomide (len) and with rituximab (R) in heavily pretreated populations (Bartlett 2022; Ward 2022). The double-blind, global phase 3 ECHELON-3 study (NCT04404283) compared BV with R+len (R2) vs R2 in pts with R/R DLBCL who are ineligible for HSCT or CAR T-cell therapy. Here, we present results from the interim analysis (IA) for overall survival (OS). Methods: Pts with R/R DLBCL received BV+R2 or placebo+R2 (randomized 1:1). Pts received BV (1.2 mg/kg) or placebo q3w, R (375 mg/m 2 ) q3w, and len (20 mg) qd. The primary endpoint was OS in the intent-to-treat population. Secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. The preplanned IA was performed at 134 OS events with a prespecified efficacy boundary of 2-sided P=0.0232. Results: 230 pts were randomized: 112 to BV+R2 and 118 to R2; all but 2 pts (both in R2 arm) received ≥1 dose of study drug. Median age was 71 yrs (range, 21-89), 56.5% were male, and 10.9% had an ECOG of 2. Median prior lines of therapy was 3 (range, 2-8); 29% had prior CAR T-cell therapy and 68% were CD30- (<1% CD30 tumor expression). At median follow-up of 16.4 months (mos) (range, 0.1-31.5) (cut-off: January 22, 2024), median OS was 13.8 mos (95% CI: 10.3-18.8) with BV+R2 vs 8.5 mos (95% CI: 5.4-11.7) with R2 (HR 0.629; 95% CI: 0.445-0.891; P=0.0085); OS benefit was consistent across key subgroups. Median PFS was 4.2 mos (95% CI: 2.9-7.1) with BV+R2 vs 2.6 mos (95% CI: 1.4-3.1) with R2 (HR 0.527; 95% CI: 0.380-0.729; P<0.0001). ORR was 64.3% (95% CI: 54.7-73.1) with BV+R2 vs 41.5% with R2 (95% CI: 32.5-51.0; P=0.0006); CR rate was 40.2% vs 18.6%, respectively. In CD30+ vs CD30- subgroups, ORR/CR was 72.2%/38.9% vs 60.5%/40.8% with BV+R2, respectively, and 50.0%/26.3% vs 37.5%/15.0% with R2, respectively. Efficacy analysis including cell of origin will be presented. The safety profile of BV+R2 was tolerable vs R2: Grade (Gr) ≥3 treatment-emergent adverse events (TEAEs) were 88% vs 77%, serious TEAEs were 60% vs 50%, and Gr 5 TEAEs were 12% vs 8%, respectively. Most common TEAEs were neutropenia (46% vs 32%), anemia (29% vs 27%), and diarrhea (31% vs 23%). Rates of peripheral neuropathy for BV+R2 vs R2 were 31% vs 24% (all Gr) and 6% vs 2% (Gr 3). Median treatment duration was 3.6 mos with BV+R2 vs 2.0 mos with R2. Conclusions: Treatment with BV+R2 triplet, compared to R2, demonstrated statistically significant and clinically meaningful improvements in all key efficacy outcomes including OS in high-risk subgroups, with manageable safety. This triplet regimen represents a novel treatment option for pts with heavily pretreated R/R DLBCL. Clinical trial information: NCT04404283 .
Long-term primary CNS lymphoma (PCNSL) survivors could have multiple adverse prognostic factors at diagnosis such as age, performance status (PS), site of the tumour (deep vs superficial), lactate dehydrogenase (LDH) level and CSF protein level. Whether these five prognostic factors integrated in the International Extranodal Lymphoma Study Group (IELSG) score have a time-dependent effect is questionable. Among 132 PCNSL patients treated at our institution between 1984 and 2006, 91 available patients for IELSG score were evaluated by time-segmented analysis. Of the 91 patients, 21% had 0-1, 59% had 2-3 and 20% had 4-5 adverse IELSG prognostic scores. With a median follow-up of 102 months, the median overall survival (OS) of the 91 patients with the five prognostic factors of IELSG score was 33 months (95% CI, 17 to 55) compared with 14 months (95% CI, 3 to 23) for the remaining 41 patients whose CSF protein level was lacking in the IELSG score. These 41 patients who did not have lumbar puncture presented a poorer PS at diagnosis and a lower treatment response rate. While confirming the prognostic value of the IELSG score, we observed a time-dependent effect of age, PS and tumour site; all three lost their prognostic value after 6 months from diagnosis, while LDH remained a constant predictor of OS. No prognostic impact of CSF protein level was reported. Patients with older age, poor PS and deep brain involvement are at risk of death during the first months after diagnosis but could have a favourable long-term outcome after the treatment period. New prognostic factors predicting long-term outcome remain to be determined.
// Cédric Rossi 1, 2 , Morgane Mounier 3 , Pauline Brice 4 , Violaine Safar 5 , Emmanuelle Nicolas-Virelizier 6 , Philippe Rey 6 , Aspasia Stamatoullas-Bastard 7 , Marion Alcantara 7 , Adrien Chauchet 8 , Emilie Reboursière 9 , Lauriane Filliatre 10 , Aurore Perrot 10 , Sylvain Garciaz 11 , Gilles Salles 6 , Bertrand Coiffier 6 , Hervé Ghesquières 5, 6 and René-Olivier Casasnovas 1, 12 1 Hématologie Clinique, CHU Le Bocage, Dijon, France 2 INSERM UMR 1037 - Cancer Research Center of Toulouse, Toulouse, France 3 Registre des Hémopathies Malignes de Côte d’Or, EA4184, Université de Bourgogne, Dijon, France 4 Hématologie Clinique, CHU Paris-GH St-Louis Lariboisière F-Widal - Hôpital Saint-Louis, Paris, France 5 Hématologie Clinique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France 6 Hématologie Clinique, Centre Régional de Lutte Contre le Cancer Léon Bérard, Lyon, France 7 Hématologie Clinique, Centre Henri Becquerel, Rouen, France 8 Hématologie Clinique, CHU Besançon, Besançon, France 9 Hématologie Clinique, CHU Caen, Caen, France 10 Hématologie Clinique, CHRU Nancy, Nancy, France 11 Hématologie Clinique, Institut Paoli-Calmettes, Marseille, France 12 INSERM UMR 1231, Université Bourgogne Franche-Comté, Dijon, France Correspondence to: Cédric Rossi, email: cedric.rossi66@gmail.com Keywords: Hodgkin lymphoma, infradiaphragmatic, radiotherapy Received: March 21, 2017 Accepted: June 19, 2017 Published: July 19, 2017 ABSTRACT Introduction: Infradiaphragmatic Hodgkin Lymphoma (IDHL) accounts for 3-11% of adult cases of stage I-II Hodgkin Lymphoma and the treatment strategy in IDHL is still heterogeneous. All previous published studies were conducted before the PET-CT era. PET may provide a more accurate evaluation of IDHL stage. The aim of this study was to analyze the clinical and biological characteristics of IDHL patients staged by CT scan or PET-CT in eight French hematology departments and their impact on outcomes in these patients. Methods: Baseline clinical and biological data and outcomes in patients with a first diagnosis of stage I-II IDHL treated with ABVD +/- radiotherapy were retrospectively collected. Results: Among the 99 patients included, 65 (66%) were staged with PET-CT. These patients were older (53 years vs 46 years, p=0.043), had lower ESR (27 vs 58mm, p=0.022), higher hemoglobin level (13.6 vs 12.8g/dL, p=0.015), less frequent Ann Arbor stage II (74% vs 91%) and less central adenopathy involvement (60% vs 82%, p=0.024). Treatment was chemotherapy alone in 55% of patients and the remaining patients received chemo-radiotherapy (CRT). Five-year PFS and OS rates in PET-CT-staged patients were 78% (95% CI 64-87) and 88% (95% CI 73-95), respectively, compared with 65% (p=0.225) and 82% (p=0.352) in CT-staged patients. The CRT strategy was associated with fewer relapses (p=0.027). Conclusion: This study showed that the characteristics of CT-staged IDHL patients were less favorable than those of PET-CT-staged patients and indicated that CRT provided better PFS than did chemotherapy alone.
Background: In 2010, we reported that the standard IPI developed in the pre-rituximab era remains valid also for DLBCL patients (pts) treated with R(ituximab) plus CHOP (Ziepert et al., JCO 2010; 28: 2373) This study included 1,062 pts with aggressive B-cell lymphoma treated with R-CHOP-14, R-CHOP-21, or dose-escalated R-MegaCHOEP. Here we studied a much larger group of DLBCL pts treated with R-CHOP or variants and compared IPI, R-IPI, and NCCN-IPI to determine which scoring system best identifies subgroups with favorable and poor outcomes that might be well treated with R-CHOP (low-risk) or might benefit most from new approaches (high-risk group). Methods: Individual pt data from 7 multicenter trials (1998-2009) of pts with BCL (86% DLBCL) treated front-line with R-CHOP (or variant) were analyzed to determine whether IPI, R-IPI, or NCCN-IPI best discriminated overall survival (OS). The concordance index (c-index) from a proportional hazards model, stratifying on trial and induction therapy, quantified predictive accuracy of each scoring system. Results: 2561 pts (median age 63 yrs, 56% male) were classified into IPI, R-IPI, and NCCN-IPI risk groups (Table). With a median follow-up of 5 yrs, NCCN-IPI had the greatest absolute difference in OS estimates between the highest and lowest risk groups at 1, 3, and 5 yrs, and best discriminated OS (c-index = 0.631, Table). Conclusions: In an independent and large cohort of pts, NCCN-IPI performed best in risk-stratifying pts with BCL, readily distinguishing pts at high and low risk for treatment failure using clinical parameters (5-yr OS between 48 and 92%). Improvement over the simpler IPI was moderate, and IPI may remain a valuable alternative. Pts with low NCCN-IPI have quite favorable survival outcomes and there is little space for further improvement. Work integrating molecular features of the tumor into the (NCCN-) IPI is in progress to better characterize a high risk group where targeted novel approaches are needed most. Keywords: diffuse large B-cell lymphoma (DLBCL). Disclosures: Schmitz, N: Consultant Advisory Role: Riemser, Takeda, Janssen, Gilead, Novartis; Stock Ownership: Celgene; Honoraria: Riemser, Takeda, Janssen, Gilead, Novartis.
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