DLBCL,   FL

A standardized comparison of SCHOLAR-1 versus ZUMA-1 and interim results from a phase II study of tazemetostat – oral abstracts in R/R DLBCL and FL at SOHO 2017

The fifth Annual Meeting of the Society of Hematologic Oncology (SOHO) took place at the Westin Galleria in Houston, Texas, between 13th–16th September 2017.

In 2012, SOHO was established and the society “aims to promote worldwide research, education, prevention, clinical studies and optimal patient care in all aspects of hematologic malignancies and related disorders.” SOHO has over 2,000 members and is led by a Board of Directors with six voting members, a Steering Committee of clinician-scientists, a Scientific Committee, and an Education Committee.

The 2017 meeting was a dynamic and informative event with internationally recognized speakers representing the spectrum of hem-onc diseases. This year, it is thought that over 1,000 physicians, nurses, and related healthcare specialists attended the 3.5-day event.

The eighth session of the meeting was dedicated to Non-Hodgkin Lymphoma (NHL), took place on 15th September 2017, and was co-chaired by Simon Rule, MD, from Derriford Hospital, Plymouth, UK, and Barbara Pro, MD, from Northwestern University, Chicago, Illinois, USA.

Two abstracts on Relapsed or Refractory (R/R) NHL, in particular Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) were presented during this session.

NHL-023 ­– SCHOLAR-1 versus ZUMA-1: a standardized comparison of outcomes in patients with refractory, aggressive NHL1

This abstract was presented by Sattva Neelapu, MD, from the University of Texas MD Anderson Cancer Center, Houston, USA. SCHOLAR-1 was an international, retrospective, multi-cohort study and found consistent poor outcomes for patients with refractory NHL (read more here). ZUMA-1 is the first, multicenter trial of an anti-CD19 Chimeric Antigen Receptor (CAR) T-cell therapy (KTE-19, axicabtagene ciloleucel, axi-cel) in refractory NHL. The Lymphoma Hub has reported on the primary results of the trial presented at AACR by Frederick L. Locke (view here), at ICML by Sattva Neelapu (view here), and at EHA by Yi Lin (view here).

  • Eligible pts in both studies had refractory NHL (SD or PD as best response to last previous therapy, or relapse within 1 year post-ASCT)
  • ZUMA-1, 10 pts received KTE-C19; SCHOLAR-1, 508 pts included
  • In ZUMA-1 versus SCHOLAR-1: age ≥65 years (24% vs 15%), primary refractory (2% vs 20%), refractory to ≥2L (77% vs 62%), relapse <12 months post-ASCT (21% vs 18%), median prior lines of therapy (3 vs 2), ECOG PS 0–1 (100% vs 80%), and IPI score ≥2 (73% vs 66%)
  • ZUMA-1 median follow-up = 8.7 months
  • SCHOLAR-1: estimated ORR = 20%; estimated CR = 6%; standardized 6-month survival rate = 35%
  • Risk of death in ZUMA-1 was reduced by 77% relative to SCHOLAR-1 (P < 0.0001)

The group acknowledge that there are imbalances between the two studies; however, KTE-C19 seems to be a “significantly improved treatment option for patients with rNHL” versus current strategies assessed in SCHOLAR-1.

Abstract:

The SCHOLAR-1 (Crump, ASCO 2016) pooled analysis of rNHL demonstrated poor outcomes: objective response rate (ORR), 26%; complete response (CR), 8%. ZUMA-1 is the first, multicenter trial of anti-CD19 CAR T cells (axicabtagene ciloleucel, axi-cel) in rNHL and reported positive results: ORR, 82%; CR, 54%; 6-month OS, 80% (Locke, Neelapu, et al. AACR, 2017).

NHL-255 – Interim report from a phase II multicenter study of tazemetostat, an EZH2 inhibitor: clinical activity and favorable safety2

This abstract was presented by Sarit Assouline, MD, a member of our Innovation Committee, from the McGill University, Montreal, Quebec and reported interim results (as of June 1st 2017) from an open-label, multicenter, phase II study which aimed to determine the efficacy and safety of the potent, selective, EZH2 inhibitor tazemetostat.

  • Eligible pts had mutated or Wild Type (WT) EZH2 R/R DLBCL or FL (n=210)
  • Tazemetostat administered po BID, 800mg
  • Grade ≥3 treatment-emergent AEs reported in 18% of pts
  • Most common (>10%) all-grade AEs = nausea, thrombocytopenia, anemia, cough, and fatigue
  • ORR results (n=203):
    • DLBCL with mutated EZH2 (n=17) = 29%
    • DLBCL with WT EZH2 (n=119) = 15%
    • FL with mutated EZH2 (n=13) = 92%
    • FL with WT EZH2 (n=54) = 26%

This oral abstract presentation concluded by stating that tazemetostat appears to be tolerable and demonstrated preliminary clinical activity, especially in patients harboring mutated EZH2. Patient follow-up continues in order to monitor any delayed responses or response evolution.

In May of this year, tazemetostat was granted Fast Track Designation by the U.S. Food and Drug Administration (read more here.)

Abstract:

New treatments with novel mechanisms of action are needed for patients with relapsed/refractory (R/R) DLBCL and FL. These tumor cells may depend on the histone methyltransferase EZH2 to perpetuate a less-differentiated state, and activating mutations may be oncogenic drivers. Tazemetostat, a potent, selective EZH2 inhibitor, shows antitumor activity in preclinical models and a phase 1 study in patients (pts) with mutated or wild-type (wt) EZH2 tumors.

References
  1. Neelapu S. et al. SCHOLAR-1 versus ZUMA-1: A Standardized Comparison of Outcomes in Patients (Pts) with Refractory, Aggressive Non-Hodgkin Lymphoma (rNHL). Clinical Lymphoma, Myeloma, and Leukemia. 2017 Sep; 17(suppl 2):S362–S363. DOI: http://dx.doi.org/10.1016/j.clml.2017.07.197.
  2. Morschhauser F. et al. Interim Report from a Phase 2 Multicenter Study of Tazemetostat, an EZH2 Inhibitor: Clinical Activity and Favorable Safety in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma. Clinical Lymphoma, Myeloma, and Leukemia. 2017 Sep; 17(suppl 2):S380–S381. DOI: http://dx.doi.org/10.1016/j.clml.2017.07.227.