Inotuzumab ozogamicin and donor lymphocyte infusion is a safe and promising combination in relapsed acute lymphoblastic leukemia after allogeneic stem cell transplant

Papayannidis, Cristina; Sartor, Chiara; Dominietto, Alida; Zappone, Elisabetta; Arpinati, Mario; Marconi, Giovanni; Cristiano, Gianluca; Nanni, Jacopo; Parisi, Sarah; Barbato, Francesco; Paolini, Stefania; Soverini, Simona; Terragna, Carolina; Robustelli, Valentina; Testoni, Nicoletta; Chirumbolo, Gabriella; Curti, Antonio; Cavo, Michèle; Bonifazi, Francesca

doi:10.1002/hon.2886

Cited by 11 publications

(9 citation statements)

References 10 publications

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“…Wiley retrospectively analyzed eight patients who relapsed post‐HSCT and received InO followed by donor lymphocyte infusion. 6/8 (75%) patients obtained MRD negative CR after the second cycle of InO 12 . Hence, InO is a preferential option for the treatment of r/r B‐ALL.…”

Section: Discussionmentioning

confidence: 99%

Preemptive inotuzumab ozogamicin eradicated measurable residual disease in Ph‐negative acute lymphoblastic leukemia relapsed post CD19 CART therapy

Huang,

Wan,

Cao

et al. 2023

Clinical Case Reports

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Section: Discussionmentioning

confidence: 99%

Preemptive inotuzumab ozogamicin eradicated measurable residual disease in Ph‐negative acute lymphoblastic leukemia relapsed post CD19 CART therapy

Huang,

Wan,

Cao

et al. 2023

Clinical Case Reports

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“…Data from an Italian registry showed a median relapse-free survival of 12 months in a total of 8 patients that were treated with this combination. 59 Schroeder et al and Leubert et al have reported interesting results with improved survival in AML and MDS patients, relapsed after transplant. Patients received subcutaneous azacitidine followed by unmanipulated DLI.…”

Section: Role Of Cellular Therapymentioning

confidence: 98%

Post-Hematopoietic Cell Transplantation Relapsed Acute Lymphoblastic Leukemia: Current Challenges and Future Directions

Varadarajan¹,

Pierce²,

Scheuing³

et al. 2023

OTT

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Allogeneic hematopoietic cell transplantation (allo-HCT) represents an important and potentially curative treatment option for adult patients with acute lymphoblastic leukemia. Relapse continues to remain the most important factor influencing overall survival post allo-HCT. We discuss early identification, clinical manifestations, and management of relapsed disease. Routine evaluation of measurable residual disease (MRD) and change in donor chimerism play a crucial role in early detection. Pivotal clinical trials have led to FDA approval of multiple novel agents like blinatumomab and inotuzumab. Combining targeted therapy with cellular immunotherapy serves as the backbone for prolonging overall survival in these patients. Donor lymphocyte infusions have traditionally been used in relapsed disease with suboptimal outcomes. This review provides insight into use of cellular therapy in MRD positivity and decreasing donor chimerism. It also discusses various modalities of combining cellular therapy with novel agents and discussing the impact of chimeric antigen receptor T-cell therapy in the setting of post allo–HCT relapse both as consolidative therapy and as a bridge to second transplant.

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“…Similarly, in another study describing the combination of InO and escalating doses of DLI in 8 adults with B-ALL who relapsed after allogeneic HSCT, no patients experienced VOD/SOS. Of note, six out of eight patients treated with this approach obtained MRD negativity after the 2nd course of InO, which was long-lasting in 4 of them (54). Thrombocytopenia is another known toxicity which may limit the application of InO in the post-transplant setting, especially for those patients experiencing delayed platelet recovery (53).…”

Section: Blinatumomab and Ino In The Post-hsct Settingmentioning

confidence: 99%

Bispecific Antibodies and Other Non-CAR Targeted Therapies and HSCT: Decreased Toxicity for Better Transplant Outcome in Paediatric ALL?

Kállay¹,

Algeri

Buechner

et al. 2022

Front. Pediatr.

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This review will address the place of innovative, non-chemotherapy, non-CAR-T targeted therapies in the treatment of Acute Lymphoblastic Leukaemia (ALL), focusing on their use in the hematopoietic stem cell transplant (HSCT) context. The focus will be on the agent with the most experience to date, namely the bispecific T-cell engater (BiTE) blinatumomab, but references to antibody-drug conjugates (ADCs) such as inotuzumab ozogamicin and monoclonal antibodies such as daratumamab will be made as well. Specific issues to be addressed include: (1) The use of these agents to reduce measurable residual disease (MRD) prior to HSCT and their potential for improved transplant outcomes due to reduced toxicity compared to traditional chemotherapy salvage, as well as potentially increased toxicity with HSCT with particular agents; (2) the appropriate sequencing of innovative therapies, i.e., when to use BiTEs or antibodies versus CARs pre- and/or post-HSCT; this will include also the potential for impact on response of one group of agents on response to the other; (3) the role of these agents particularly in the post-HSCT relapse setting, or as maintenance to prevent relapse in this setting; (4) special populations in which these agents may substitute for traditional chemotherapy during induction or consolidation in patients with predisposing factors for toxicity with traditional therapy (e.g., Trisomy 21, infants), or those who develop infectious complications precluding delivery of full standard-of-care (SOC) chemotherapy during induction/consolidation (e.g., fungal infections); (5) the evidence we have to date regarding the potential for substitution of blinatumomab for some of the standard chemotherapy agents used pre-HSCT in patients without the above risk factors for toxicity, but with high risk disease going into transplant, in an attempt to decrease current rates of transplant-related mortality as well as morbidity; (6) the unique toxicity profile of these agents and concerns regarding particular side effects in the HSCT context. The manuscript will include both the data we have to date regarding the above issues, ongoing studies that are trying to explore them, and suggestions for future studies to further refine our knowledge base.

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Inotuzumab ozogamicin and donor lymphocyte infusion is a safe and promising combination in relapsed acute lymphoblastic leukemia after allogeneic stem cell transplant

Cited by 11 publications

References 10 publications

Preemptive inotuzumab ozogamicin eradicated measurable residual disease in Ph‐negative acute lymphoblastic leukemia relapsed post CD19 CART therapy

Preemptive inotuzumab ozogamicin eradicated measurable residual disease in Ph‐negative acute lymphoblastic leukemia relapsed post CD19 CART therapy

Post-Hematopoietic Cell Transplantation Relapsed Acute Lymphoblastic Leukemia: Current Challenges and Future Directions

Bispecific Antibodies and Other Non-CAR Targeted Therapies and HSCT: Decreased Toxicity for Better Transplant Outcome in Paediatric ALL?

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