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.
BACKGROUND: The outcomes of patients with relapsed or refractory (R-R) acute lymphoblastic leukemia (ALL) are poor. Inotuzumabozogamicin 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.
Authors: Hagop Kantarjian; Anthony Stein; Nicola Gökbuget; Adele K Fielding; Andre C Schuh; Josep-Maria Ribera; Andrew Wei; Hervé Dombret; Robin Foà; Renato Bassan; Önder Arslan; Miguel A Sanz; Julie Bergeron; Fatih Demirkan; Ewa Lech-Maranda; Alessandro Rambaldi; Xavier Thomas; Heinz-August Horst; Monika Brüggemann; Wolfram Klapper; Brent L Wood; Alex Fleishman; Dirk Nagorsen; Christopher Holland; Zachary Zimmerman; Max S Topp Journal: N Engl J Med Date: 2017-03-02 Impact factor: 91.245
Authors: Jonathan A C Sterne; Ian R White; John B Carlin; Michael Spratt; Patrick Royston; Michael G Kenward; Angela M Wood; James R Carpenter Journal: BMJ Date: 2009-06-29
Authors: Hagop M Kantarjian; Daniel J DeAngelo; Matthias Stelljes; Giovanni Martinelli; Michaela Liedtke; Wendy Stock; Nicola Gökbuget; Susan O'Brien; Kongming Wang; Tao Wang; M Luisa Paccagnella; Barbara Sleight; Erik Vandendries; Anjali S Advani Journal: N Engl J Med Date: 2016-06-12 Impact factor: 91.245
Authors: Shannon L Maude; Theodore W Laetsch; Jochen Buechner; Susana Rives; Michael Boyer; Henrique Bittencourt; Peter Bader; Michael R Verneris; Heather E Stefanski; Gary D Myers; Muna Qayed; Barbara De Moerloose; Hidefumi Hiramatsu; Krysta Schlis; Kara L Davis; Paul L Martin; Eneida R Nemecek; Gregory A Yanik; Christina Peters; Andre Baruchel; Nicolas Boissel; Francoise Mechinaud; Adriana Balduzzi; Joerg Krueger; Carl H June; Bruce L Levine; Patricia Wood; Tetiana Taran; Mimi Leung; Karen T Mueller; Yiyun Zhang; Kapildeb Sen; David Lebwohl; Michael A Pulsipher; Stephan A Grupp Journal: N Engl J Med Date: 2018-02-01 Impact factor: 91.245
Authors: Anthony H Goldstone; Susan M Richards; Hillard M Lazarus; Martin S Tallman; Georgina Buck; Adele K Fielding; Alan K Burnett; Raj Chopra; Peter H Wiernik; Letizia Foroni; Elisabeth Paietta; Mark R Litzow; David I Marks; Jill Durrant; Andrew McMillan; Ian M Franklin; Selina Luger; Niculae Ciobanu; Jacob M Rowe Journal: Blood Date: 2007-11-29 Impact factor: 22.113
Authors: Erica Brivio; Franco Locatelli; Marta Lopez-Yurda; Andrea Malone; Cristina Díaz-de-Heredia; Bella Bielorai; Claudia Rossig; Vincent H J van der Velden; Anneke C J Ammerlaan; Adriana Thano; Inge M van der Sluis; Monique L den Boer; Ying Chen; Barbara Sleight; Benoit Brethon; Karsten Nysom; Lucie Sramkova; Ingrid Øra; Luciana Vinti; Christiane Chen-Santel; Christian Michel Zwaan Journal: Blood Date: 2021-03-25 Impact factor: 22.113
Authors: Benjamin A Derman; Mitchell Streck; Joseph Wynne; Trevor N Christ; Emily Curran; Wendy Stock; Randall W Knoebel Journal: Leuk Lymphoma Date: 2019-11-04