Crizotinib In Advanced Alk Plus Anaplastic Large Cell Lymphoma In Children And Adults: Results Of The Acs (C) Phase Ii Trial

Background: Crizotinib (czb) has shown significant clinical activity in relapsed/refractory ALK+ ALCL in small cohorts of patients (pts) but this drug has yet to be approved for the treatment of these pts in Europe. To avoid off-label use and allow for a nationwide access to czb for pts with ALK+ tumor including ALK+ ALCL, the French National Cancer Institute (INCa) launched the AcSe program, funding both access to tumor molecular diagnosis and an exploratory multi tumor phase II trial. We report the results of the ALCL cohort. Methods: All pts u003e 1 year (yr) of age with advanced ALK+ ALCL and measurable disease who were not amenable to curative treatment could be included in the trial providing they had adequate hematologic, renal and hepatic functions and had recovered from toxicities of previous treatment (Tt). A two-stage Simon design was planned with a 90% power to detect an objective response rate at 2 cycles (completed response (CR) + partial response (PR)) above 40% against a 20% rate at the 10% level. Responses were assessed every 8 weeks. All imaging were centrally reviewed. Dose of czb was 250 mg BID in adults and 165 mg/m 2 BID in children. Results: Among 17 pts enrolled from Feb. 2014 to June 2017, 2 did not receive czb (one early death before the first czb administration and one consent withdrawal) and 15 are evaluable for response. Median age is 21 yr (1-60 yr) with 6 pts under age 18. The median number of prior chemotherapy lines was 2 including brentuximab in 10 pts (66%) and a stem cell autotransplant in 3 pts. Seven pts were had refractory ALCL as defined by disease progression during frontline Tt, 6 were enrolled after one or several relapses with a median time between end of Tt and 1 st relapse of 3.5 months (m) and 2 critically ill pts were included for frontline Tt after failure of steroid based prephase. Among the 15 evaluable pts, 10 achieved an objective response (67%, CI95% [42%-85%]) (9CR, 1PR) and 5 experienced a disease progression. The response rate was similar in pts under 18 (4/6, 67%, CI95% [24%, 94%]) and in adults (6/9, 67%, CI95% [31%, 91%]). The median duration of Tt was 3.7 m for the entirecohort and 6.5 m for pts who achieved a response (20 d - 23 m); 2 pts remained on Tt for more than 11 m at the date of last follow-up and 13 have stopped czb (5 for progression, 5 for alloSCT, 3 for maintenance with other drugs). All tumor progressions during czb Tt occurred within 3 m from Tt and 3/5 occurred in pts with refractory disease. Among the 10 pts who achieved a response, 3/8 progressed after czb discontinuation and 7 remain in complete remission. With a median follow-up of 12 m, the median progression free survival is 11.6 m (CI95% [1.41, NA]). Overall 4 pts died and 11 are still alive. Czb was well tolerated with 5 grade (gr) ≥ 3 AEs; one patient with gr 3 hematological toxicities and one patient with gr 3 cytolysis. The mainAEs related to czb were gr 1 (75% of AE), including nausea/vomiting (15%), elevated transaminases (11%), visual disorders (11%). Conclusion Crizotinib proved well tolerated and able to induce durable objective responses in most ALCL pts. During crizotinib treatment all progressions occurred during the first 3 months. Disclosures Morschhauser: Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Servier: Consultancy; Gilead: Consultancy.