Type: Oral
Session: 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies I
Hematology Disease Topics & Pathways:
Clinical Trials, Lymphoid Leukemias, ALL, Clinical Research, Clinically Relevant, Diseases, Lymphoid Malignancies
Between 8/2017-4/2021 770 pts from 78 centers were included and 705 were evaluable. The median age was 35 (18-55) yrs, 638 had ALL (B,Ph-: 55%, Ph+: 20%, T: 25%,) and 67 pts LBL (B:12%; T:88%). For ALL the hematologic (Hem) CR rate after C1 was 93% and the MolCR Rate 61% (75% mol. response) (table 1). HemCR rate was 72% in LBL with 21% PR. PET CT was negative in half of the LBL PR cases. The lowest HemCR rate was observed in early T-ALL (83%) together with a MolCR rate of 45% (71% mol. response).
In Ph- pts 2000 U/m2 as first dose ASP was administered in 66%, 500 U/m2 in 24%, no ASP in 1% and other doses in 9%. In pts with Ph+ ALL the respective numbers were 61%, 21%, 6% and 13%. For the 2nd dose the numbers were 43%, 21%,13% and 22% for Ph- and 41%, 24%, 13% and 22% for Ph+ pts. Bilirubine increases grade III/IV were observed in Ph- ALL in 18% of the cases treated with 500 U/m2 vs 24% for 2000 U/m2. In Ph+ ALL the respective numbers were 5% vs 3%. GOT/GPT grade III/IV increases were observed 29% of Ph- ALL pts treated with 500 U/m2 vs 25% of those with 2000 U/m2. The respective numbers for Ph+ ALL were 24% and 40%.
At a median follow-up of 23 mo, the overall survival (OS) for all pts (N=705) was 88% and 76% at 1 and 3 yrs resp (subgroups see table 1). OS was correlated to age, 87%, 74%, 69% and 73% at 3 yrs for pts aged 18-25, 26-35, 36-45 and 46-55 yrs resp. SR T-ALL reached an OS of 86% at 3 yrs with a conventional and nelarabine based consolidation. 79% of pts with an indication for SCT were transplanted (64 sibling, 174 MUD). The OS of SCT pts after SCT was 75% at 3 yrs.
63 pts with MolFail became candidates for a targeted therapy, which was realized in 89% of the cases. The molecular response was evaluable in 51 pts and reached 55% (N=40) and 18% (N=11) after one cycle of Blinatumomab or Nelarabin resp. Pts with MolFail (N=63) achieved an OS of 84% at 1y and 72% at 3 years resp (71% for Ph- and 76% for Ph+).
This large, ongoing prospective multicenter trial provides promising preliminary results. This applies also to those aged 45-55 yrs underlining that adult pts beyond the variable AYA definitions can benefit from pediatric-based therapy. Intensive and individualized ASP therapy was feasible. Whereas high HemCR rates were observed in nearly all subgroups, MolCR rates ranged from 41-74% and a relevant proportion remained MRD low positive underlining the need for detailed MRD classification. MRD-based targeted treatment was realized in a high proportion of pts. Responses to Blinatumomab in MolFail were lower compared to previous trials. Responses to Nelarabine in MolFail T-ALL pts were only 18%. OS of MolFail pts however was promising with the combination of targeted therapy and SCT. Thus, SCT is still a key component, contributing to improved outcomes although the overall proportion of SCT was lower than in previous GMALL trials.
Disclosures: Goekbuget: Astra Zeneca: Other: Invited talk for company sponsored symposia (with honor); Gilead/Kite: Consultancy; Abbvie: Other; Morphosys: Consultancy; Erytech: Consultancy; Incyte: Other: Research funding for Institution; Cellestia: Consultancy; Jazz Pharmaceuticals: Other: Research funding for institution; Pfizer: Consultancy, Other: Research funding for institution; Novartis: Consultancy, Other: Research funding for Institution; Amgen: Consultancy, Other: Invited talks for company sponsored symposia (with honoraria); Research funding for institution; Servier: Consultancy, Other. Stelljes: Pfizer: Consultancy, Research Funding, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau. Viardot: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; University Hospital of Ulm: Current Employment; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Nachtkamp: Jazz: Honoraria; Bsh medical: Honoraria; Celgene: Other: Travel Support. Topp: Novartis: Consultancy; Roche: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy; Amgen: Consultancy, Research Funding; Macrogeniecs: Research Funding; Regeneron: Consultancy, Research Funding; Gilead: Research Funding; Universitatklinikum Wurzburg: Current Employment. Wäsch: BMS/Celgene: Consultancy; Gilead: Consultancy; Novartis: Consultancy; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy. Vucinic: Abbvie: Honoraria, Other: Travel Sponsoring; MSD: Honoraria; Janssen: Honoraria, Other: Travel Sponsoring; Gilead: Honoraria, Other: Travel Sponsoring; Novartis: Honoraria. Baldus: Novartis: Honoraria; Amgen: Honoraria; Celgene/BMS: Honoraria; Jazz: Honoraria. Brüggemann: Amgen: Other: Advisory Board, Travel support, Research Funding, Speakers Bureau; Incyte: Other: Advisory Board; Janssen: Speakers Bureau. Pfeifer: Incyte: Honoraria, Research Funding. Schwartz: Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau; Novartis: Speakers Bureau; Jazz Pharmaceuticals: Other: Travel grants, Speakers Bureau; BTG International Inc: Membership on an entity's Board of Directors or advisory committees; MSD Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Basilea: Other: Travel grants; Gilead: Other: Travel grants, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Morphosys: Research Funding. Fiedler: Abbvie: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material; Amgen: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material, Patents & Royalties, Research Funding; Ariad/Incyte: Honoraria; Celgene: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material; MorphoSys: Consultancy, Honoraria; Novartis: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Daiichi Sanyko: Consultancy, Other: Meeting attendance, Preparation of information material; Stemline: Consultancy; Servier: Consultancy, Other: Meeting attendance, Preparation of information material.
OffLabel Disclosure: Nelarabine in newly diagnosed T-ALL