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Clinical Trial
. 2023 May 2;16(1):44.
doi: 10.1186/s13045-023-01444-2.

Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia

Hagop Kantarjian  1 , Fadi G Haddad  2 , Nitin Jain  2 , Koji Sasaki  2 , Nicholas J Short  2 , Sanam Loghavi  3 , Rashmi Kanagal-Shamanna  3 , Jeffrey Jorgensen  3 , Issa Khouri  4 , Partow Kebriaei  4 , Yesid Alvarado  2 , Tapan Kadia  2 , Shilpa Paul  5 , Guillermo Garcia-Manero  2 , Bouthaina Dabaja  6 , Musa Yilmaz  2 , Jovitta Jacob  2 , Rebecca Garris  2 , Susan O'Brien  7 , Farhad Ravandi  2 , Elias Jabbour  2
Affiliations
Clinical Trial

Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia

Hagop Kantarjian et al. J Hematol Oncol. .

Abstract

Background: Historically, adults with relapsed-refractory acute lymphoblastic leukemia (ALL) experienced poor outcomes with intensive chemotherapy. This mature analysis explores the benefit of the addition of sequential blinatumomab to low-intensity mini-Hyper-CVD chemotherapy with inotuzumab ozogamicin in this setting.

Methods: Mini-Hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 83% dose reduction) was combined with inotuzumab during the first 4 courses. From Patient #68 and onwards, inotuzumab was given in reduced and fractionated doses, and blinatumomab was added sequentially for 4 courses. Maintenance therapy with prednisone, vincristine, 6-mercaptopurine and methotrexate was given for 12 courses, and blinatumomab for 4 additional courses.

Results: Among 110 patients (median age, 37 years) treated, 91 (83%) responded (complete response, 69 patients, 63%). Measurable residual disease negativity was documented in 75 patients (82% of responders). Fifty-three patients (48%) received allogeneic stem cell transplantation (SCT). Hepatic sinusoidal obstruction syndrome occurred in 9/67 patients (13%) on the original inotuzumab schedule and in 1/43 (2%) on the modified schedule. With a median follow-up of 48 months, the median overall survival (OS) was 17 months, and the 3 year OS was 40%. The 3 year OS was 34% with mini-Hyper-CVD plus inotuzumab and 52% with additional blinatumomab (P = 0.16). By landmark analysis at 4 months, the 3 year OS was 54%, similar between patients who did or did not receive allogeneic SCT.

Conclusion: Low-intensity mini-Hyper-CVD plus inotuzumab with or without blinatumomab showed efficacy in patients with relapsed-refractory ALL, with better survival after the addition of blinatumomab. Trial registration The trial was registered on clinicaltrials.gov with the identifier NCT01371630.

Keywords: Blinatumomab; Chemo-immunotherapy; Inotuzumab; Outcome; Philadelphia-negative ALL; Salvage.

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Conflict of interest statement

HK: Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Research Funding; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Immunogen: Research Funding; Amgen: Honoraria, Research Funding; Novartis: Research Funding; Takeda: Honoraria; Ariad: Research Funding; Agios: Honoraria, Research Funding; Astex: Research Funding; BMS: Research Funding; Daiichi-Sankyo: Research Funding. The rest of authors has no competing conflicts of interests. NJ: Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, an AbbVie company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. KS: Otsuka: Honoraria; Pfizer: Consultancy; Daiichi-Sankyo: Consultancy. NJS: Takeda Oncology: Consultancy, Research Funding; AstraZeneca: Consultancy; Amgen: Honoraria. YA: Jazz Pharmaceuticals: Research Funding; Abbott: Honoraria. TK: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bioline RX: Research Funding; BMS: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. GGM: Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. SO: Astellas: Consultancy; Alexion: Consultancy; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Celgene: Consultancy; Sunesis: Consultancy, Research Funding; Kite: Research Funding; Aptose Biosciences, Inc: Consultancy; Acerta: Research Funding; Verastem: Consultancy; GlaxoSmithKline: Consultancy; Eisai: Consultancy; Vaniam Group LLC: Consultancy; TG Therapeutics: Consultancy, Research Funding; Regeneron: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Amgen: Consultancy. FR: Xencor: Consultancy, Research Funding; Menarini Ricerche: Research Funding; Selvita: Research Funding; Cyclacel LTD: Research Funding; Macrogenix: Consultancy, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. EJ: AbbVie: Consultancy, Research Funding; Cyclacel LTD: Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. FGH, SL, RKS, JJ, IK, PK, SP, BD, MY, JJ, and RG declare no competing interests.

Figures

Fig. 1
Fig. 1
Survival outcome A overall, B by treatment modality, C by Salvage status, D by best MRD status, E by allogeneic stem cell transplantation, and F in comparison with inotuzumab monotherapy. S1 Salvage 1; S2 + Slavage 2 and beyond; Neg Negative; Pos Positive; Ino Inotuzumab; Blina Blinatimomab; Rtx Rituximab
Fig. 1
Fig. 1
Survival outcome A overall, B by treatment modality, C by Salvage status, D by best MRD status, E by allogeneic stem cell transplantation, and F in comparison with inotuzumab monotherapy. S1 Salvage 1; S2 + Slavage 2 and beyond; Neg Negative; Pos Positive; Ino Inotuzumab; Blina Blinatimomab; Rtx Rituximab
See this image and copyright information in PMC

References

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