EBMT 2022 | Stem cell boost for persistent cytopenia after CAR-T therapy

Chimeric antigen receptor T-cells, or CAR-T, have shown a dramatic efficacy as we all know in treating refractory aggressive B-cell lymphoma, DLBCL, and has already been approved by the EMA here in Europe for axi-cel and tisa-cel and new therapies are coming every month, basically. But persistent cytopenia is a frequently observed complication after this therapy, including profound and prolonged neutropenia in approximately two-thirds of the patients, which may subsequently further increase the risk for infection. To date, there is limited data on the value of hematopoietic stem cell boosts for persistent cytopenia. There are only some small case series, but we tried to evaluate this in a systematic fashion using a multicenter cohort of the German Lymphoma Alliance, and we present here at the EBMT, the first results for patients who have received stem cell boosts between 2018 and 2021 for persistent cytopenia, and they received either axi-cel or tisa-cel.

This first analysis included 15 patients who received either axi-cel, these were nine patients, or tisa-cel, six patients, and most of the patients had DLBCL. The median age was 61 years, and most patients as expected had a low ECOG performance status in accordance with the trials that were published for the approval of these therapies. The median time between the CAR-T infusion and the stem cell boosts was about one month. One patient also received an allogeneic stem cell boost from a matched related donor, after having received an allogeneic stem cell transplant before CAR-T therapy. The median number of the infused cells was about 4 million per kilogram body weight and we found that the median time to neutrophil engraftment was five days, which was quite short, and is quite a promising result. The early application of the stem cell boost within the first two months was correlated with sustainable blood counts and seemed to be associated with a better outcome overall. In total, only eight patients died and there were two treatment-related deaths due to sepsis. Both patients who died of sepsis had grade 4 neutropenia for more than two months, and this is a signal that we need to be aware of the duration of the neutropenia that we identify. If we have the feeling that the neutropenia is long lasting, we should maybe consider a stem cell boost. The overall median follow-up of these CAR-T infusion patients was 15 months and the median overall survival was 20 months. In conclusion, this is the first multicenter trial on stem cell boosts for persistent cytopenia, and it demonstrates that the stem cell boosts generally result in a prompt resolution of cytopenia and is safe. This provides evidence that the prolonged cytopenia after CAR-T is due to dysfunction of hematopoietic stem or progenitor cells rather than to immunological effects. These stem cell boosts should be considered for persistent cytopenia after CAR-T therapy, if it’s available, of course.