Chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD, with or without blinatumomab, is highly effective in patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first salvage.
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| Abstract | BACKGROUND: The outcomes of patients with relapsed or refractory (R-R) acute lymphoblastic leukemia (ALL) are poor. Inotuzumab ozogamicin and blinatumomab have single-agent activity in R-R ALL. Their addition to low-intensity chemotherapy may further improve the outcomes of patients with ALL in their first relapse. METHODS: The chemotherapy was lower in intensity than conventional hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone and was called mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone (or mini-HCVD). Inotuzumab was given on day 3 of each of the first 4 cycles at 1.8 to 1.3 mg/m2 for cycle 1, and this was followed by 1.3 to 1.0 mg/m2 for subsequent cycles. From patient 39 onward, the inotuzumab dose was reduced and fractionated into weekly doses (0.6 and 0.3 mg/m2 during cycle 1 and 0.3 and 0.3 mg/m2 during subsequent cycles), and blinatumomab was administered for up to 4 cycles after inotuzumab therapy. RESULTS: Forty-eight patients with Philadelphia chromosome-negative ALL with a median age of 39 years were treated during their first relapse. Overall, 44 patients (92%) responded, with 35 of them (73%) achieving a complete response. The overall minimal residual disease negativity rate among the responders was 93%. Twenty-four patients (50%) underwent allogeneic stem cell transplantation (ASCT). Veno-occlusive disease of any grade occurred in 5 patients (10%). With a median follow-up of 31 months, the median progression-free survival (PFS) and the median overall survival (OS) were 11 and 25 months, respectively. The 2-year PFS and OS rates were 42% and 54%, respectively. Of the 24 patients (50%) who underwent ASCT, 14 patients were alive at the last follow-up (13 [54%] in remission). Of the remaining 20 responding patients who did not undergo subsequent ASCT, 6 (30%) remained in remission at the last follow-up. According to propensity score matching, the combination of mini-HCVD and inotuzumab with or without blinatumomab conferred better outcomes than intensive salvage chemotherapy or inotuzumab alone. CONCLUSIONS: The combination of inotuzumab and low-intensity mini-HCVD chemotherapy with or without blinatumomab shows encouraging results in patients with ALL in first salvage.
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| Authors | Elias Jabbour, Koji Sasaki, Farhad Ravandi, Xuelin Huang, Nicholas J Short, Maria Khouri, Partow Kebriaei, Jan Burger, Joseph Khoury, Jeffrey Jorgensen, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Jorge Cortes, Jovitta Jacob, Kathryn Montalbano, Rebecca Garris, Susan O'Brien, Hagop M Kantarjian |
| Journal | Cancer (Cancer) Vol. 124 Issue 20 Pg. 4044-4055 (10 15 2018) ISSN: 1097-0142 [Electronic] United States |
| PMID | 30307611 (Publication Type: Clinical Trial, Phase II, Journal Article) |
| Copyright | © 2018 American Cancer Society. |
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