ASCO 2018 | The Highlights 

Follicular Lymphoma

• PHASE III RELEVANCE study (abstract 7500) – Nathan Fowler
  • R2 (rituximab + lenalidomide) vs R-chemo followed by rituximab maintenance in patients with ND FL
  • 1,030 patients included
  • Efficacy results were similar (ORR, CRu, DoR)
  • No superiority of R2 vs R-chemo in terms of PFS at 120 weeks
  •  More Grade 3 / 4 neutropenia in the R-chemo arm (50%) compared with R2 (32%)
  • Longer follow-up needed for mature PFS and OS data
  • Summary – Expert’s interview
• Current advances in FL – Sonali Smith
  • Results of the RELEVANCE trial: longer follow-up needed
  • New PI3K inhibitor approved in the US (copanlisib)
  • Expert’s interview
• Polatuzumab vedotin in combination with BR (abstract 7507) – Laurie Sehn
  • Randomized controlled trial against BR – 80 R/R FL patients
  • Increase of low grade AEs (peripheral neuropathy) and grade 3-5 AEs (neutropenia, anemia and febrile neutropenia [but no infection])
  • No difference in CRR, mPFS and mOS
  •   Expert’s interview
• Phase 1b/2 of Hu5F9-G4 (abstract 7504) – Ranjana Advani
  • Hu5F9-G4: first-in-class anti-CD47 antibody (5F9)
  • 7 patients with R/R FL
  • MTD not reached
  • In combination with rituximab: CRR = 43%, mDoR not reached
  • Summary 

DLBCL

• TRANSCEND NHL 001 study (abstract 7505) – Jeremy Abramson
  • JCAR017 (lisocabtagene maraleucel)
  • 102 patients included with R/R aggressive NHL
  • DLBCL cohort: ORR = 80%, CRR = 59%
  • 93% patients in remission at 6 months remained in remission at the latest follow-up
  • Most important Grade 3 / 4 events = neutropenia and fatigue, CRS: 37%, NE: 23%
  •  Summary
• Durable responses with axi-cel in R/R DLBCL in the ZUMA-1 trial (abstract 3003) – Frederick Locke
  • 108 patients treated with axi-cel (axicabtagene ciloleucel), follow-up: 15.4 months
  • ORR = 82%, CRR = 58%, mDoR = 11.1 months
  • Responders at 3 months have 80% chance to maintain their response at 1 year. Some PR converted into CR at 1 year
  • Summary - Expert’s interview
• Polatuzumab vedotin in combination with BR (abstract 7507) – Laurie Sehn
  • Randomized controlled trial against BR – 80 R/R DLBCL patients
  • Increase of low grade AEs (peripheral neuropathy) and grade 3-5 AEs (neutropenia, anemia and febrile neutropenia [but no infection])
  • CRR: 40% (vs 15%), mPFS: >6 months (vs 2 months), mOS: >11 months (vs <5 months)
  •  Expert’s interview
• Phase 1b/2 of Hu5F9-G4 (abstract 7504) – Ranjana Advani
  • Hu5F9-G4: first-in-class anti-CD47 antibody (5F9)
  • 15 patients with R/R FL
  • MTD not reached
  • In combination with rituximab: CRR = 33%, mDoR not reached
  • Summary

HL

• Final analysis of the AHL2011 LYSA trial (abstract 7503) – Olivier Casasnovas
  • 823 patients included with untreated HL – early PET-driven treatment de-escalation after 2 cycles of BEACOPPesc vs not PET-     monitored strategy
  • mFU: 50.4 months – 4-y PFS: 87.1% vs 87.4%; 5-y PFS: 85.7% vs 86.2%; 4-y OS: 97.1% vs 96.9%; 5-y OS: 96.4% vs 95.2%
  • Summary – Expert’s interview – G. Salles’s interview
• Novel therapies for R/R HL beyond transplant – Catherine Diefenbach
  • Not all relapsed patients are the same
  • 1st relapse and ASCT = SoC but for patients in CR2
  • BV: 35% CRR in 2nd line salvage prior to SCT, effective in consolidation post AST (mPFS: 42.9% vs 24.1%, but no difference in mOS)
  • BV + B: CRR: 76%, 18-months PFS: 75%
  • Nivolumab: CRR between 9% and 17%
  • BV + ipi: CRR = 48%, 1-y PFS = 58%
  • BV + nivo: CRR = 67%, 6-months PFS = 93%
  • Other new agents tested (mTORi, HDACi)
  • Allo-SCT: 3-y OS = 50% but 20% mortality
  •   Expert’s interview
• Risk-adapted treatment strategies for advanced-stage HL – Joseph Connors
  • Brentuximab vedotin improves effectiveness of CT (improvement of curability?)
  • New agents tested in poorest prognostic patients
  • Expert’s interview

CLL

• Ibrutinib and venetoclax in treatment-naïve CLL (abstract 7502) – William Wierda
  • Undetectable MRD in 77% patients after 6 cycles and 79% after 12 cycles
  • No new safety signals
  •   Summary – Expert’s interview
• High and durable MRD- with venetoclax and rituximab in R/R CLL (abstract 7508) – Peter Hillmen
  • MRD-: VenR = 84% vs BR = 23%
  • 83% of patients maintained MRD-, regardless of risk features
  • Expert’s interview
• The potential of venetoclax for patients with 17p deletion – Michael Hallek
  • Studied in high-risk patients (17p deleted. P53 mutated or complex karyotype)
  • Venetoclax in combination with rituximab (Murano trial) or ibrutinib (Captivate trial) or obinutuzumab induce long-lasting remissions (several years in the Murano trial) and MRD-
  •  Expert’s interview
• Role of chemo-immunotherapy in CLL – Susan O’Brien
• Relapse setting;
  • no role for chemotherapy
  • Retreatment with FCR or BR
  • Ibrutinib for 17p and 11q deleted patients
  • VenR
• Front-line setting: SoC = FCR
  • Patients with IgVH mutation: FCR
  • Fit unmutated and elderly patients : ibrutinib
• Expert’s interview

MISCELLANEOUS

FL

• Retrospective analysis on biopsy-proven FL transformation in the rituximab era – Marek Trnĕný
  • 1200 patients with FL, 546 relapses, 370 tFL; risk of transformation is ≈10%
  • Rituximab might reduce the risk of transformation
  • Expert’s interview
• Definition and management of high-risk FL patients – Stefano Luminari
  • The most important prognostic factor is the duration of response
  • Early relapses have to be considered as aggressive disease (intensified treatment with ASCT)
  •   Expert’s interview

DLBCL

• Real-time CoO subtype identification by genetic profiling (abstract 7548) – Greg Nowakowski
  • Feasible on a global scale (mean time: 2.6 days) – ROBUST phase III trial
  • Incidence of ABC (355-38% in the US, 40% in Europe and 60% in Asia)
  • Expert’s interview
• Tailored therapy for aged patients with aggressive lymphoma – Raoul Cordoba
  • 3 different prognostic factors identified: age, IPI and co-morbidities to define 3 risk-groups: robust (to be treated as younger patients), vulnerable or frail
  •   Expert’s interview

DLBCL, FL

• Overview of immunotherapy – Carol Jacobson
  • TRANSCEND study: CRR = 50%
  • Phase I monoclonal antibody anti CD47 + rituximab in FL, DLBCL
  • ORR = 50%, CR in 1/3 of patients. Very good safety profile
  • Expert’s interview

CTCL

• Novel therapies for CTCL – Francine Foss
  • BV (ALCANZA trial) efficient even in patients with very low expression of CD30
  • Mogamulizumab (anti CCR4), especially efficient in SZ
  • Other investigational agents (targeting CD25 or mRNA155)
  • Expert’s interview

WM

• Acalabrutinib in monotherapy (abstract 7501) – Roger Owen
  • Efficient in treatment-naïve patients: 93% ORR, 24-months duration of response rate = 90%, 90% 24-m PFS, 24-m OS = 92%
  • Activity in R/R patients: 93% ORR, 24-months duration of response rate = 84%, 82% 24-m PFS, 24-m OS = 89%
  • Most common grade ≥3 AEs: neutropenia, pneumonia and low respiratory tract infection
  • Summary

CLL, FL and WM

• Potential for CT-free future – Bruce Cheson
  • FL: R2 regimen; WM: acalabrutinib; CLL: doublets with rituximab idelalisib, ibrutinib or venetoclax
  • Expert’s interview