Phase II trial of mini-hyper-CVD-inotuzumab (InO) followed by blinatumomab (blina) consolidation in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL).

person Cedric Christophe Nasnas Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Cedric Christophe Nasnas, Elias Jabbour, Fadi Haddad, Nicholas James Short, Walid Macaron, Marianne Zoghbi, Lewis Fady Nasr, Nitin Jain, Emmanuel Almanza, Koji Sasaki, Farhad Ravandi, Partow Kebriaei, Xuelin Huang, Guillermo Garcia-Manero, Tapan M. Kadia, Sa A Wang, Jovitta Jacob, Rebecca Garris, Susan M. O'Brien, Hagop M. Kantarjian

Authors person Cedric Christophe Nasnas Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Cedric Christophe Nasnas, Elias Jabbour, Fadi Haddad, Nicholas James Short, Walid Macaron, Marianne Zoghbi, Lewis Fady Nasr, Nitin Jain, Emmanuel Almanza, Koji Sasaki, Farhad Ravandi, Partow Kebriaei, Xuelin Huang, Guillermo Garcia-Manero, Tapan M. Kadia, Sa A Wang, Jovitta Jacob, Rebecca Garris, Susan M. O'Brien, Hagop M. Kantarjian Organizations Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Department of Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA Abstract Disclosures Research Funding Institutional Funding MD Anderson Cancer Center, Amgen and pfizer Background: Promising results were seen with low intensity chemotherapy mini-Hyper-CVD (mini-HCVD) in combination with InO in R/R ALL. Adding blina may further improve outcomes. Methods: Pts with R/R Philadelphia-negative B-ALL were treated with mini-HCVD (Cycles 1, 3, 5, 7) and methotrexate/cytarabine (Cycles 2, 4, 6, 8) for 8 cycles. Initially, InO was given on Day (D) 3 of the first 4 cycles at the dose of 1.8-1.3 mg/m 2 in Cycle (C) 1, followed by 1.3-1.0 mg/m 2 in subsequent cycles. POMP maintenance was for a total of 3 yrs. Protocol was amended after pt #67 to add 4 cycles of blina after 4 cycles of mini-HCVD+InO. InO was given on D2 and 8 at the dose of 0.6 and 0.3 mg/m 2 in C1, and then on D2 and 8 at the dose of 0.3 mg/m 2 in subsequent cycles; blina was given at standard dose in C5-8. Maintenance was reduced to 12 cycles of POMP with 1 cycle of blina after each 3 cycles of POMP for a total of 4 cycles. Rituximab was given for CD20+ disease. All pts received 8 doses of intrathecal chemotherapy. Results: Between 2/2013 and 7/2021, 110 pts were treated. Patient characteristics are shown in the table. 79 (72%) pts were treated in Salvage (S) 1, and 31 (28%) in S2+. 21 (19%) pts had received prior ASCT. 91 (83%) pts responded (complete remission, 63%). The overall response rate was 93% in S1, 59% in S2, and 57% in S3+. The rates of MRD negativity by flow were higher in S1 vs S2+ (89% vs 67%; P= 0.047). 53 (48%) pts underwent ASCT. After a median follow-up of 48 months (mo) (range, 9-115), the median OS and RFS were 17 mo (4-yr, 36%) and 13 mo (4-yr, 37%), respectively. Pts in S1 had better OS compared with S2+ (4-yr OS, 43% vs 18%; P <0.001). The 4-yr RFS was 38% in S1 and 27% in S2+ ( P =0.14). In S1, 41 pts were treated before the amendment and 38 after the amendment; their 4-yr OS was 41% and 48% ( P =0.99), and their 4-yr RFS was 39% and 36%, respectively ( P =0.95). A landmark analysis of pts who achieved remission showed no survival difference between pts who did or did not undergo ASCT, with 4-yr OS of 49% and 48% ( P =0.98), and 4-yr RFS of 46% and 37% ( P =0.68), respectively. Sinusoidal obstruction syndrome (SOS) was noted in 10 (9%) pts, and its incidence decreased from 13% with single dose of InO to 2% with lower and fractionated doses of InO ( P =0.056). Conclusions: The combination of mini-HCVD and reduced-dose InO with sequential blina improved the outcomes of pts with R/R ALL. The new treatment schedule resulted in a lower rate of SOS compared to the original schedule. Clinical trial information: NCT01371630. Patient characteristics. Characteristic Median [range] / N (%) Category Pre Amendment N=67 Post Amendment N=43 Age (yrs) 34 [17-87] 42 [18-79] Status S1 S1, Primary Refractory S1, CRD1 < 12m S1, CRD1 ≥ 12m S2 ≥ S3 38 (57) 5 17 16 29 (43) 42 (93) 10 9 23 3 (7) Prior ASCT 19 (28) 2 (5) Karyotype Diploid KMT2Ar Misc IM/ND 14 (21) 8 (12) 35 (52) 10 (15) 14 (33) 2 (5) 23 (51) 6 (14) SOS 9 (13) 1 (2)