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Clinical Trial
. 2018 Oct 15;124(20):4044-4055.
doi: 10.1002/cncr.31720. Epub 2018 Oct 11.

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

Elias Jabbour  1 , Koji Sasaki  1 , Farhad Ravandi  1 , Xuelin Huang  2 , Nicholas J Short  1 , Maria Khouri  1 , Partow Kebriaei  3 , Jan Burger  1 , Joseph Khoury  4 , Jeffrey Jorgensen  4 , Nitin Jain  1 , Marina Konopleva  1 , Guillermo Garcia-Manero  1 , Tapan Kadia  1 , Jorge Cortes  1 , Jovitta Jacob  1 , Kathryn Montalbano  1 , Rebecca Garris  1 , Susan O'Brien  5 , Hagop M Kantarjian  1
Affiliations
Clinical Trial

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

Elias Jabbour et al. Cancer. .

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.

Keywords: acute lymphoblastic leukemia (ALL); first relapse; inotuzumab ozogamicin; salvage.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors received research grants from Pfizer and Amgen. Pfizer provided free drug from the Pfizer Investigator Sponsored Trial program. The authors declare no other conflict of interest.

Figures

Figure 1A:
Figure 1A:
Overall survival for the whole cohort and progression-free survival
Figure 1B:
Figure 1B:
Overall survival by minimal residual status
Figure 2:
Figure 2:
Overall survival with or without subsequent allogeneic stem cell transplantation
Figure 3A:
Figure 3A:
Progression-free survival by therapy: mini-HCVD plus inotuzumab +/− blinatumomab versus standard chemotherapy using propensity score matching
Figure 3B:
Figure 3B:
Overall survival by therapy: mini-HCVD plus inotuzumab +/− blinatumomab versus standard chemotherapy using propensity score matching
Figure 3C:
Figure 3C:
Progression-free survival by therapy: mini-HCVD plus inotuzumab +/− blinatumomab versus inotuzumab monotherapy using propensity score matching
Figure 3D:
Figure 3D:
Overall survival by therapy: mini-HCVD plus inotuzumab +/− blinatumomab versus inotuzumab monotherapy using propensity score matching
See this image and copyright information in PMC

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