Researchers in Blood Advances sought to explore the transfusion needs for patients who received Chimeric antigen receptor (CAR) T-cell therapy to treat larger B-cell lymphoma (LBCL). They explained that blood products in the form of red blood cells (RBCs) or platelets, “have been reported in [approximately] 55 percent to 66 percent of patients after CAR T-cell infusion, but little is known about the specific needs, complications, and outcomes in this population.” They also explained that the efficacy of CAR T-cells may be impacted by transfusions due to, “a phenomenon called transfusion-related immunomodulation.” This study aimed to, “describe the transfusion needs in patients receiving commercial anti-CD19 CAR T-cell therapy for LBCL in the real-world setting. Secondary objectives are to search for predictive factors associated with transfusion needs after CAR T-cell therapy and to examine the potential correlation between transfusion needs and CAR T-cell efficacy and toxicity.”
Patients included in this study were, “treated for relapse or refractory (R/R) BCL with commercial CD19 CAR T-cells registered in the DESCAR-T database, presenting with at least a six-month follow-up after infusion, and for whom exhaustive transfusion data were available.” This database is the national registry in France for data collection for individuals who receive CAR T-cells “outside of clinical trials.” The authors specified that, “[p]atients were censored for transfusions at relapse, new treatment onset, or death. We distinguished transfusions received at the early phase, meaning during the first month after CAR T-cell infusion; and at the late phase, meaning beyond the first and until the sixth month.” The researchers explained that from, “August 2018 to September 2022, a total of 671 patients registered in the DESCAR-T registry [met] the eligibility criteria. They found that, [a]t the time of CAR T-cell infusion, median age was 63 years (range, 18-82) [and overall,] 82.7 percent of patients received a bridging therapy, which consisted of systemic chemotherapy in 85.2 percent of cases.”
Almost 60 percent of patients (401 individuals) received a blood product transfusion at some point during the six months prior to their first CAR T-cell treatment. Specifically, 357 (53.2 percent) received RBCs, and 301 (44.9 percent) received platelets transfusion. The number of patients receiving transfusion increased month by month to reach a maximum of 228 patients (34.0 percent) within the month before treatment (30.3 percent requiring RBC and 19.2 percent platelets transfusion). The mean number of transfused RBCs and platelets units per month in the six-month period before CAR T-cell infusion also increased progressively to reach 1.0 (range, 0-15) and 0.7 (range, 0-29) during the month before infusion, respectively.
After CAR T-cell infusion, 378 patients (56.3 percent) received transfusion: 345 (51.4 percent) received RBC transfusion and 280 (41.7 percent) received platelets transfusion. The highest transfusion needs were at the early phase (i.e., within in the first month), with 359 patients (53.5 percent) requiring at least one transfusion, including 317 (47.2 percent) for RBC and 252 (37.6 percent) for platelets). During the early phase, the mean number of transfused RBCs and platelets units were 1.6 (range, 0-13) and 2.3 (range, 0-44), respectively. At the late phase (i.e., between one and six months after infusion), 202 patients (36.7 percent) received transfusion, including 172 (31.3 percent) for RBCs and 181 (32.9 percent) for platelets. The mean number of transfused units decreased over time after CAR T-cell infusion. Beyond the third month, transfusion needs were very low with only 22 patients (6.0 percent) requiring at least one transfusion (4.7 percent for RBC and 4.9 percent for platelets).”
The investigators described four categories developed for patients based on, “the time between CAR-T infusion and transfusion (early <1 month vs late ≥1 month and until 6 months) and the type of transfused product (RBCs vs platelets).” They found that, [n]either overall response rate (ORR) nor complete response (CR) were statistically different between patients who received transfusion and non-transfused patients, at early and late phase after CAR T-cell infusion. However, early transfusions were associated with a shorter progression-free survival (PFS) for RBCs (median PFS, 3.1 vs 6.0 months; P = .0042) and platelets (median PFS, 3.1 vs 5.8 months; P = .0054). Late platelets transfusion also affected PFS (median PFS, 5.6 vs 12.0 months; P = .0072), whereas late RBC transfusion did not (median PFS, 8.8 vs 8.5 months; P = .7199). Similarly, early transfusions were associated with a shorter overall survival (OS) for RBCs (median OS, 9.0 vs 21.1 months; P < .0001) and platelets (median OS, 7.8 vs 21.1 months; P < .0001). Late platelets transfusion also affected OS (median OS, 13.8 months vs not reached; P < .0001), whereas late RBC transfusion did not (median OS, 20.6 vs 24.1 months; P = .0971).” Additionally, the study showed that, “[c]umulative incidence of lymphoma-related mortality was significantly higher for patients receiving early RBC and/or platelets transfusion and late platelets transfusion but not late RBC transfusion. Cumulative incidence of non-relapse mortality (NRM) was significantly higher for patients receiving early and late platelet transfusion and late (but not early) RBC transfusion. Indeed, NRM was [approximately] two times higher for patients receiving early RBC transfusion (12.3 percent vs 8.2 percent; P = .095), early platelets transfusion (14.3 percent vs 7.6 percent; P = .008), late RBC transfusion (14.0 percent vs 6.9 percent; P = .010), and late platelets transfusion (14.9 percent vs 6.2 percent; P = .001).”
The authors concluded that, “[o]ur study provides an accurate description of transfusion needs in patients with LBCL treated with CD19 CAR T-cell therapy. We identified risk factors associated with early and late transfusion needs after CAR T-cell infusion, mainly CAR-HEMATOTOX score, pre–CAR T-cell transfusion needs, high-grade immune effector cell-associated neurotoxicity syndrome (ICANS), and tocilizumab use. Finally, our study sheds light on the potential impact of transfusions on CAR T-cell efficacy and toxicity. Our results may help inform the management of patients treated with CAR T-cell and support strategies that reduce transfusion needs after CAR T-cell therapy.” They noted that limitations of this study included, “some data are missing, especially regarding baseline cytopenia and inflammatory markers that did not allow for us to calculate the CAR-HEMATOTOX score in [approximately] 10 percent of the patients. Data regarding bone marrow infiltration and duration of neutropenia were only available in very few cases. Finally, data from the DESCAR-T registry mostly include routine laboratory tests, so we were not able to analyze CAR T-cell expansion and causes of relapse that could have helped us to better understand the association between transfusion and outcome.” A commentary on this paper has also been published in Blood Advances.
Citation: Vic, S. Jean-Baptiste, T., Bachy, E., et al. “Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study).” 2024.