Authors: Lewis Fady Nasr, Nicholas James Short, Jayastu Senapati, Yesid Alvarado Valero, Nitin Jain, Marina Konopleva, Walid Macaron, Farhad Ravandi, Courtney Denton Dinardo, Koji Sasaki, Alessandra Ferrajoli, Cedric Christophe Nasnas, Marianne Zoghbi, Jovitta Jacob, Ejiroghene Mayor, Anna Milton, Christopher Loiselle, Rebecca Garris, Hagop M. Kantarjian, Elias Jabbour
Published: 2023-06-04
DOI: 10.1200/jco.2023.41.16_suppl.e19008
Source: Full article
e19008 Background: INO is effective in relapsed/refractory B-ALL and may have utility in eradicating MRD in patients (pts) in MRD-positive (MRD+ve) remission. Methods: This is a phase II trial of pts with B-ALL in complete remission (CR) with persistent MRD+ve or with MRD+ve relapse. Eligible pts were required to be MRD+ve at ≥0.01%. MRD negativity (MRD-ve) was defined as undetectable MRD by flow cytometry (sensitivity 10-4) for Philadelphia (Ph)-negative (Ph-) B-ALL and undetectable MRD by both flow and PCR for BCR:ABL1 for Ph-positive (Ph+) B-ALL. INO was given at a dose of 0.6 mg/m2 on D1 and 0.3 mg/m2 on D8 of cycle 1 and 0.3 mg/m2 on D1 and 8 of subsequent cycles (up to 6 total cycles, given every 21-28 days) along with ursodiol prophylaxis. Pts with Ph+ ALL received concomitant TKI. Results: 27 pts with MRD+ve B-ALL were treated between 11/2018 and 6/2022 (Table). 17 pts (63%) had Ph+ B-ALL (15 received ponatinib and 2 dasatinib), and 10 pts had Ph- B-ALL. 20 pts (74%) were in CR1, and 7 pts (26%) were in CR2 or beyond. 14 pts (52%) had received prior blinatumomab and 5 pts (18%) had prior stem cell transplantation (SCT). 18 pts (67%) became MRD-ve (responders), 16 after the 1st cycle and 2 after the 2nd cycle of INO. In the Ph+ group, 10/17 pts (59%) responded; another 3 pts achieved major molecular response. 8/10 (80%) pts with Ph- B-ALL responded. The median number of cycles of INO were 3 (range, 1-6). Rates of MRD response were higher in pts without prior blinatumomab (11/13 pts [80%]), compared with those with prior blinatumomab exposure (7/14 [50%]) ( P=0.06). After a median follow-up of 21 months, 13/18 responding pts (72%) are in ongoing MRD-ve CR. Among the 18 responders, 6 pts underwent allogeneic stem cell transplant (ASCT) after a median of 3 cycles of INO (range, 1-4); all were in MRD-ve CR at the time of ASCT. 4/18 responders (22%) relapsed, 1 of whom relapsed after ASCT. Median RFS and OS for the whole group were not reached; estimated 2-year RFS and OS were 61% and 62%, respectively. 2-year OS for responders and non-responders were 76% and 50% (P=0.34), respectively. 2-year RFS for pts with or without prior blinatumomab was 23% and 91%, respectively; P=0.04. No grade 4 non-hematological toxicities were observed. 1 pt (who had a history of prior ASCT) had grade 3 sinusoidal obstruction syndrome. Conclusions: Low-dose, fractionated INO is effective at eradicating MRD in pts with B-ALL and can result in durable MRD-ve remissions. Clinical trial information: NCT03441061 . [Table: see text]