Allogeneic CD34-selected stem cell boost as salvage treatment of life-threatening infection and severe cytopenias after CAR-T cell therapy.

BACKGROUND: A variable incidence of profound cytopenia has been described in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). This complication leads to severe infection in some cases, especially those who present additional risk factors including prior hematopoietic stem cell transplantation (HSCT). STUDY DESIGN AND METHODS: We report a case of breakthrough invasive fungal infection in a patient with prolonged neutropenia after CAR-T cell therapy administered for relapsed B-cell ALL after allogeneic haploidentical HSCT. RESULTS: After disease progression was discarded, therapy with antifungal agents, G-CSF and thrombopoietin analogue was started. However, no sign of haematological recovery or infection improvement was observed. A fresh mobilized selected CD34-stem cell boost from her haploidentical transplant donor was infused without further conditioning. Within 15 days of mobilized CD34-boost administration the patient showed complete resolution of both the aplasia and fungal infection. DISCUSSION: This case illustrates as proof-of-concept the efficacy and safety of selected CD34-stem cell boost from prior donor as salvage treatment of prolonged cytopenias after CAR-T cell therapy.

IBRORS-MCL study: a Spanish retrospective and observational study of relapsed/refractory mantle-cell lymphoma treated with ibrutinib in routine clinical practice.

This retrospective study evaluated 66 patients diagnosed with relapsed and/or refractory mantle cell lymphoma (R/R MCL) treated with ibrutinib in Spain in routine clinical practice. At diagnosis, patients had a median age of 64.5 years, 63.6% presented with intermediate/high sMIPI (simplified prognostic index for advanced-stage mantle cell lymphoma), 24.5% had the blastoid variant, and 55.6% had a Ki67 > 30%. Patients had received a median of 2 prior lines of therapy (range 1-2; min-max 1-7). Overall response rate was 63.5%, with 38.1% of patients achieving complete response (CR). With a median duration of ibrutinib exposure of 10.7 months (range 5.2-19.6; min-max 0.3-36), the median progression-free survival (PFS) and overall survival (OS) were 20 months [95% confidence interval (CI) 8.8-31.1] and 32 months (95% CI 22.6-41.3), respectively, and were not reached in patients achieving CR. No grade ≥ 3 cardiovascular toxicity or bleeding was reported. This study supports that treatment with ibrutinib leads to high response rates and favorable survival outcomes in patients with R/R MCL.

Use of Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia: The PETHEMA Registry Experience.

The effectiveness of venetoclax (VEN) in relapsed or refractory acute myeloid leukemia (RR-AML) has not been well established. This retrospective, multicenter, observational database studied the effectiveness of VEN in a cohort of 51 RR-AML patients and evaluated for predictors of response and overall survival (OS). The median age was 68 years, most were at high risk, 61% received ≥2 therapies for AML, 49% had received hypomethylating agents, and ECOG was ≥2 in 52%. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi), was 12.4%. Additionally, 10.4% experienced partial response (PR). The CR/CRi was higher in combination with azacitidine (AZA; 17.9%) than with decitabine (DEC; 6.7%) and low-dose cytarabine (LDAC; 0%). Mutated NPM1 was associated with increased CR/CRi. Median OS was 104 days (95% CI: 56-151). For the combination with AZA, DEC, and LDAC, median OS was 120 days, 104 days, and 69 days, respectively; p = 0.875. Treatment response and ECOG 0 influenced OS in a multivariate model. A total of 28% of patients required interruption of VEN because of toxicity. Our real-life series describes a marginal probability of CR/CRi and poor OS after VEN-based salvage. Patients included had very poor-risk features and were heavily pretreated. The small percentage of responders did not reach the median OS.

Management of adverse effects of new monoclonal antibody treatments in acute lymphoblastic leukemia.

Therapeutic options for relapsed/refractory B-cell acute lymphoblastic leukemia have evolved in the past few years. The FDA has approved three novel therapies for this disease: inotuzumab ozogamicin (an anti-CD22 antibody-drug conjugate), blinatumomab (a bispecific T-cell engager), and chimeric antigen receptor T-cell therapy. Although these novel immunotherapies have revolutionized the therapeutic landscape, it is important to understand the crucial aspects of administration, especially toxicity. In this article, we review the unique toxicities and adverse effects of blinatumomab and inotuzumab ozogamicin and provide recommendations for prevention of adverse effects as well as the management options for each medication.

Use of anti-CD20 therapy in follicular and marginal zone lymphoma: a review of the literature.

The identification of the CD20 antigen in 1979 was the first step in what would become a therapeutic milestone opening the use of immunotherapy in hematological diseases. This protein is expressed on the surface of developing B cells, but not the early progenitors or mature plasma cells. In 1997, rituximab was approved by the Food and Drug Administration, and since then it has revolutionized the treatment of B-cell malignancies. It is used as a monotherapy and in combination, at induction, at relapsed, and also in maintenance. Indolent non-Hodgkin lymphomas are characterized by a long and non-aggressive course. In this group of lymphomas, rituximab represented a great therapeutic improvement, achieving lasting responses with few adverse effects. Nowadays, second-generation molecules are emerging that may have important advantages compared to rituximab, as well as biosimilars that represent an important cost-effective option.