Blinatumomab and Inotuzumab Ozogamicin Sequential Use for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Real-Life Campus All Study

Author:

Fracchiolla Nicola Stefano1ORCID,Sciumè Mariarita1ORCID,Papayannidis Cristina2,Vitale Antonella3,Chiaretti Sabina3,Annunziata Mario4ORCID,Giglio Fabio5,Salutari Prassede6,Forghieri Fabio7,Lazzarotto Davide8ORCID,Lunghi Monia9,Imovilli Annalisa10,Scappini Barbara11,Bonifacio Massimiliano12ORCID,Dargenio Michelina13,Gurrieri Carmela14,Todisco Elisabetta15,Defina Marzia16,Del Principe Maria Ilaria17ORCID,Zappasodi Patrizia18,Cerrano Marco19ORCID,Santoro Lidia20,Tagliaferri Elena1,Barozzi Enrico21ORCID,De Roberto Pasquale1,Canzi Marta1,Buzzatti Elisa17ORCID,Sartor Chiara2ORCID,Passamonti Francesco121ORCID,Foà Robin3,Curti Antonio2

Affiliation:

1. Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy

2. IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “L. & A. Seràgnoli”, 40138 Bologna, Italy

3. Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy

4. Hematology Unit, Azienda Ospedaliera Cardarelli, 11411 Naples, Italy

5. Division of Onco-Hematology, European Institute of Oncology, IRCCS, 20141 Milan, Italy

6. Hematology Unit, Ospedale Civile Santo Spirito, 65100 Pescara, Italy

7. Department of Medical and Surgical Sciences, Section of Hematology, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia, 41125 Modena, Italy

8. Division of Hematology, University Hospital-ASUFC, 33100 Udine, Italy

9. Division of Hematology, Department of Translational Medicine, AOU Maggiore della Carità, Università del Piemonte Orientale, 13100 Novara, Italy

10. Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS, 42123 Reggio Emilia, Italy

11. Hematology Unit, Department of Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi, University of Florence, 50121 Florence, Italy

12. Department of Medicine, Section of Hematology, University of Verona, 37129 Verona, Italy

13. Hematology and Stem Cell Transplantation Unit, Vito Fazzi Hospital, 73100 Lecce, Italy

14. Dipartimento Strutturale Aziendale Medicina, University of Padova, 35122 Padua, Italy

15. Ospedale di Busto Arsizio, ASST Valle Olona, 21052 Busto Arsizio, Italy

16. Hematology Unit, University of Siena, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy

17. Hematology Unit, Department of Biomedicina and Prevention, Tor Vergata University, 00133 Rome, Italy

18. Department of Hematology Oncology, Division of Hematology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy

19. Division of Hematology, A.O.U. Città della Salute e della Scienza, 10126 Turin, Italy

20. Struttura Complessa di Ematologia e Trapianto Emopoietico, A.O.S.G. Moscati, 83100 Avellino, Italy

21. Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy

Abstract

Background: Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy. Methods: We describe 71 R/R B-ALL patients treated for different relapses with Blina and InO. Blina was the first treatment in 57 patients and InO in 14. Twenty-seven patients had a previous allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: In the Blina/InO group, after Blina, 36 patients (63%) achieved a complete remission (CR), with 42% of negative minimal residual disease (MRD−); after InO, a CR was achieved in 47 patients (82%, 34 MRD−). In the InO/Blina group, after InO, 13 cases (93%) reached a CR (6 MRD−); after Blina, a CR was re-achieved in 6 cases (43%, 3 MRD−). Twenty-six patients proceeded to allo-HSCT. In the Blina/InO group, the median overall survival (OS) was 19 months; the disease-free survival (DFS) after Blina was 7.4 months (11.6 vs. 2.7 months in MRD− vs. MRD+, p = 0.03) and after InO, 5.4 months. In the InO/Blina group, the median OS was 9.4 months; the median DFS after InO was 5.1 months and 1.5 months after Blina (8.7 vs. 2.5 months in MRD− vs. MRD+, p = 0.02). With a median follow-up of 16.5 months from the start of immunotherapy, 24 patients (34%) are alive and 16 (22%) are alive in CR. Conclusion: In our series of R/R B-ALL, Blina and InO treatment demonstrate efficacy for subsequent relapses in terms of MRD response, OS and DFS, and as a bridge to allo-HSCT.

Funder

Italian Ministry of Health—Current research IRCSS

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference31 articles.

1. National Cancer Institute (2023, March 15). Cancer Stat Facts: Leukemia—Acute Lymphocytic Leukemia (ALL), Available online: https://seer.cancer.gov/statfacts/html/alyl.html.

2. New approaches to the management of adult acute lymphoblastic leukemia;Bassan;J. Clin. Oncol.,2018

3. International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia;Dombret;Haematologica,2016

4. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia;Kantarjian;N. Engl. J. Med.,2017

5. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia;Kantarjian;N. Engl. J. Med.,2016

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