Authors: Nicholas James Short, Elias Jabbour, Nitin Jain, Fadi Haddad, Walid Macaron, Musa Yilmaz, Alessandra Ferrajoli, Tapan M. Kadia, Yesid Alvarado Valero, Abhishek Maiti, Lewis Fady Nasr, Marianne Zoghbi, Cedric Christophe Nasnas, Rebecca Garris, Min Zhao, Marina Konopleva, Farhad Ravandi, Hagop M. Kantarjian
Published: 2023-06-04
DOI: 10.1200/jco.2023.41.16_suppl.e19017
Source: Full article
e19017 Background: Consolidation with blina, regardless of measurable residual disease (MRD) status, improves overall survival (OS) in adults with newly diagnosed B-cell ALL. The addition of INO may deepen responses and further improve outcomes. Methods: Patients (pts) 14-59 years of age with newly diagnosed Ph-negative pre-B-cell ALL, including pts who had received no more than 1 prior cycle of chemotherapy, were eligible. Pts received hyper-CVAD alternating with high-dose MTX/Ara-C for up to 4 cycles, followed by 4 cycles of Blina at standard doses. Pts with CD20+ disease received 8 doses of an anti-CD20 antibody. Eight doses of prophylactic IT chemotherapy were given. Maintenance was with alternating blocks of POMP (maintenance cycles 1-3, 5-7, 9-11, and 13-15) and Blina (maintenance cycles 4, 8, and 12). Beginning with pt #39, INO at a dose of 0.3 mg/m2 on day 1 and 8 was added to the 2 cycles of MTX/Ara-C and to 2 cycles of Blina consolidation (4 total cycles with INO). Results: To date, 69 pts have been treated (38 without INO and 31 with INO). Baseline characteristics are summarized in the table. Among 53 pts with active disease at study entry, 100% achieved CR. MRD negativity by flow was achieved in 56/59 evaluable pts (95%). Of the 3 pts who did not achieve MRD negativity, 2 were later found to have a NUP214: ABL1 fusion, and 1 had KMT2A rearrangement. The median follow-up of the entire cohort is 26 months. Overall, 8 pts (12%) relapsed while on study, 22 (32%) underwent stem cell transplant (SCT) in first remission (2 of whom relapsed post-SCT), 2 (3%) died in CR, and 37 (54%) remain in continuous remission without SCT. For the entire cohort, the estimated 3-year OS was 87% and the 3-year continuous remission duration was 83%. With a median follow-up in the INO cohort of 15 months, 3 pts (10%) have relapsed, all with CNS-only relapses, and none has died. The 15-month OS in the cohorts with and without INO were 100% and 87%, respectively (P=0.06). One pt discontinued Blina due to recurrent grade 2 neurotoxicity. No pts have discontinued INO due to toxicity and no cases of SOS/VOD have been observed. Conclusions: In pts with newly diagnosed Ph-negative B-cell ALL receiving hyper-CVAD with sequential Blina, OS may be improved with the addition of INO. Clinical trial information: NCT02877303 . [Table: see text]