Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Clinical Research, Therapies, Immunotherapy
Methods: E7777 was given at 9 mcg/kg/day for 5 days every 21 days up to 8 cycles in patients with relapsed/refractory CTCL. Key inclusion/exclusion criteria: histopathologic diagnosis of CTCL; ECOG PS 0 or 1; no prior exposure to ONTAK. Evaluation of safety included incidence and severity of treatment-emergent AEs (TEAEs), and adverse events of special interest (AESIs). Key AESIs include capillary leak syndrome (CLS), infusion reaction, visual impairment (these three AEs were listed as Box warnings in the ONTAK label); and hepatotoxicity.
Results: The Primary Efficacy endpoint, ORR (95% CI) by IRC, was 36.2% (95% CI: 25.0%, 48.7%), with 8.7% achieving a CR; detailed efficacy data will be presented in a separate abstract. In the subset of patients with Stage I-III disease (n=69), the median age was 64 years and the median number of E7777 cycles received was 6 (range 1 to 42); 66 patients had mycosis fungoides and 3 had Sezary syndrome, and 39 (57%) had disease of stage IIb or worse.
The most common TEAEs were nausea (43.5%); fatigue (31.9%); and increased ALT, chills, and peripheral edema (27.5% each). Thirty patients (43.5%) had a Grade ≥3 TEAE (90% Grade 3; 10% Grade 4)). The most common serious adverse events (≥ 5%) were capillary leak syndrome (10%) and infusion reactions (9%). Overall, the mean numbers of TEAEs per subject were higher in the first 1 to 2 treatment cycles.
Most patients [92.8%] had at least 1 AESI (mostly Grade 1/2). Overall, 22 patients (31.9%) experienced AESIs that were Grade ≥3; (7.2%) had drug discontinuation; (4.3%) had drug dose reduction, and (26.1%) had drug dose interruption.
Fourteen patients (20.3%) had CLS. CLS was defined as the occurrence of at least 2 of the following: hypotension, edema, or serum albumin < 3.0 g/dL. CLS was Grade 1 in 2.9%, Grade 2 in 11.6%, Grade 3 in 4.3%, and Grade 4 in 1.4%. Nine patients (13.0%) underwent drug modification: (4.3%) discontinued E7777; and (10.1%) had either dose reduction or temporary dose interruption. CLS typically occurred in the first 1/2 cycles. Risk/severity of CLS was mitigated by fluid management; confirmation of serum albumin levels (≥ 3.0 g/dl); close monitoring of weight, edema, and BP; early drug interruption; and rapid initiation of diuretic therapy on recovery.
Fifty-one patients (73.9%) had an AESI related to infusion reaction. Grade 1 in 43.5%, Grade 2 in 26.1%, and Grade 3 in 4.3%. One patient (1.4%) had study drug discontinuation, and (11.6%) had either study drug dose reduction or interruption. In the event of infusion-related reactions, systemic corticosteroids may be added to premedication for subsequent E7777 infusions.
Nine patients (13.0%) had an event related to visual impairment; all were AEs of blurred vision, which was Grade 1 in 11.6% and Grade 2 in 1.4%; no Grades 3, 4, or 5. One patient (1.0%) had drug interruption; no events led to study drug dose reduction.
Twenty-five patients (36.2%) had AESI related to hepatoxicity. The TEAEs were Grade 1 in 17.4%, Grade 2 in 7.2%, Grade 3 in 11.6%, and no Grade 4/5. The majority of hepatic adverse events were elevations in transaminases that occurred within the first or second cycle, resolved without medical intervention, and did not require treatment discontinuation.
Conclusion: No new safety signals were observed with E7777 when compared to the safety profile of ONTAK. There is no evidence of cumulative toxicity. Most patients had at least 1 TEAE which were mostly Grade 1/2. Specific AESIs: CLS, infusion reactions, and visual impairment (prior ONTAK Box warnings) were mostly Grade 1/2 and effectively managed. Overall, E7777 was well-tolerated with the use of pre-medications, close patient monitoring, and prompt initiation of supportive measures and drug management.
Disclosures: Geskin: Eisai Inc.: Other: Clinical trial support; Kyowa Kirin: Consultancy, Honoraria, Research Funding; Mallinckrodt: Research Funding; Helsinn: Consultancy, Honoraria, Research Funding. Kuzel: CVS: Consultancy; Kyowa Kirin: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cardinal Health: Membership on an entity's Board of Directors or advisory committees; Merck-Sharpe-Dohme: Membership on an entity's Board of Directors or advisory committees; SeaGen: Membership on an entity's Board of Directors or advisory committees. Querfeld: Bristol Meyer Squibb: Other: Clinical Investigator; Trillium: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Investigator; Celgene: Research Funding; Helsinn: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Mallinckrodt: Membership on an entity's Board of Directors or advisory committees; Bioniz: Membership on an entity's Board of Directors or advisory committees. Ooi: Eisai Inc.: Current Employment. Xing: Eisai Inc.: Current Employment. Sauter: Eisai Inc.: Current Employment. Singh: Citius Pharmaceuticals Inc: Current Employment, Current holder of stock options in a privately-held company. Czuczman: Citius Pharmaceuticals Inc: Current Employment. Foss: Kyowa: Consultancy; Seagen: Consultancy, Speakers Bureau; Daiichi: Consultancy; Conjupro: Consultancy; Astex: Consultancy.
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