Inotuzumab

Advances in the prognostication, monitoring, and treatment of both the acute and chronic leukemias have led to drastically improved outcomes over the past 2 decades. With the advent of targeted therapies, including antibodies such as blinatumomab and inotuzumab and small molecule inhibitors, such as the BCR::ABL1 tyrosine kinase inhibitors, Bruton tyrosine kinase inhibitors, and venetoclax, the treatment landscape of leukemia has drastically changed, improving survival outcomes while relying less on overall chemotherapy intensity in many leukemia types. This progress has allowed the categorization of more leukemia types as favorable (i.e., chronic lymphocytic leukemia, younger acute lymphoblastic leukemia [patients younger than 60 years], and Philadelphia chromosome‐positive acute lymphoblastic leukemia) in addition to the traditional favorable subtypes of acute promyelocytic leukemia, core‐binding factor acute myelocytic leukemia, chronic myelocytic leukemia, and hairy cell leukemia. Advancements in the treatment of TP53 ‐mutated, MECOM ‐rearranged, and treated secondary AML are still needed to improve outcomes in these adverse risk groups. The authors also review the recent progress in the treatment of the acute and chronic leukemias.

Since the first approval of tisagenlecleucel in 2017, pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) may receive this CD19-directed chimeric antigen receptor T-cell therapy. We report real-world data from the Center for International Blood and Marrow Transplant Research (>2.5 years of follow-up). As of 4 May 2022, 768 patients with B-ALL had received tisagenlecleucel. Patients aged ≥18 and <18 years of age (including those <3 years) were treated during first relapse (26.6% and 26.7% [<3 years, 44.8%], respectively) or primary refractory disease (12.4% and 12.1% [<3 years, 15.5%], respectively) with 17.6% and 11.6% (<3 years, 13.8%), respectively, having high disease burden (≥50% bone marrow [BM] blasts) and 20.2% and 20.2% (<3 years, 13.8%), respectively, having low disease burden (>0 to <5% BM blasts). Among patients with ≥12 months postinfusion follow-up (n = 578; median follow-up, 32.1 months), the best overall response of complete remission/complete remission with incomplete blood count recovery was 86.0%. The 12-month relapse-free survival (RFS) and overall survival (OS) were 61.8% and 79.4%, respectively, whereas the 24-month RFS and OS were 50.3% and 63.8%, respectively. Age (<18 years) and disease burden (<50% BM blasts) were associated with better outcomes. Previous inotuzumab therapy and KMT2A rearrangement were associated with worse outcomes. Older patients (≥18 years) experienced a higher rate of any-grade cytokine release syndrome (CRS) associated with higher disease burden before infusion. Any-grade CRS and neurotoxicity were lower in patients aged <3 years. Extended follow-up continues to demonstrate high rates of RFS and favorable safety in this population.