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Infectious complications mild and not common in patients receiving CAR-T therapy for diffuse large B cell lymphoma

Presented By
Dr Roberta Di Blasi, Hospital Saint-Louis, France
EHA 2019
Dr Roberta Di Blasi (Hospital Saint-Louis, France) studied infection complications of chimeric antigen receptors T cells (CAR-T) treatment in diffuse large B cell lymphoma (DLBCL) patients [1]. She concluded that febrile neutropenia is a frequent complication and that it can be difficult to distinguish infections from beginning cytokine release syndrome (CRS). Bacterial and viral infection have low incidence and fungal infections did not occur in this cohort at all. Infectious complications appear mild and not fatal. Longer follow-up for immune recovery/infectious complications is needed, as well as broader studies to better define infectious risk in this subset of patients.

CAR-T efficacy was demonstrated in DLBCL patients by the JULIET and ZUMA1 trials [2]. Consistent with other CAR-T studies, the main toxicities observed were CRS and neurotoxicity, as well as some early and late-onset haematologic toxicities such as neutropenia, thrombopenia, and B-cell aplasia. Neutropenia occurred in 22-80% of patients across studies to date.

The objective of the study by Dr Di Blasi and colleagues was to establish the infection risk in DLBCL patients (n=29) treated with CAR-T cell therapy, especially gathering data from the first 30 days from the injection. The median age of patients was 50 (23-77) years, of whom 28% had had prior stem cell transplantation, and the median number of previous lines of treatment was 4. Out of 29 patients, 27 required a bridging chemotherapy while their CAR-T cells were being manufactured; immunochemotherapy was provided for most of these patients. All patients were treated with a fludarabine-containing lymphodepletion regimen. Prophylaxis was performed in 28/29 patients for Pneumocystis jirovecii and viral infections.

Neutropenia, lasting a median of 6 days, was present in 90% of the patients (24/29), which was complicated by fever in 76% of the patients. At day 30, 3 patients (10%) had severe neutropenia <500. Empirical antibiotics were given to 22/24 (92%) patients with for a mean duration of 10 days (range 4-22 days), and 5/29 patients presented with infection (17%) from whom 8 microbiologically confirmed specimens were derived: 4 were bacterial, 4 were viral, and 0 were fungal; 2 patients had 2 or more concomitant infections. Of the bacterial infections identified, 1 patient had a polymicrobial gram + bloodstream infection (BSI) consisting of E.fecalis + S.epidermidis attributable to cholangitis, and this same patient also had C.difficilis enteritis. Another patient had S.epidermidis BSI with concomitant deep venous catheter infection, while yet another patient had E.coli pneumonia.

There were 4 isolates confirming viral infections in 3 patients, 1 patient had Rhinovirus upper respiratory tract infection, 1 patient had Norovirus enteritis, and 1 patient had CMV reactivation + BK virus cystitis. Interestingly, all 5 patients with infections presented with non-severe CRS (grade <2).

Of all febrile patients, 42% (10/24) were transferred to the ICU, with a mean stay of 7 days (3-12). Poor outcomes were observed in 2 of the 24 patients at day 30; 1 had progressive disease and infection (BSI) and died, and another patient had a CMV-positive PCR test at day 30 was treated with foscarnet. 19/24 patients without microbiological documentation of infection showed spontaneous improvement and resolution of their febrile event. No mortality was attributable to infections complications alone.

Dr Di Blasi continued with the data for 90-day follow-up, reported here for the first time. After the patients went home, they were in the care of their family doctor. Of the 28 living patients, 1 upper respiratory tract infection (not microbiologically documented) was treated with antibiotics at home, and 1 patient developed P.jirovecii pneumonia (no prophylaxis). 20/29 patients had a persistent response with regard to their haematological disease (not retreated) at day 90. 8/20 patients (40%) had at least one episode of grade 3-4 neutropenia between 30-60 days after infusion.

    1. Di Blasi R, et al. Abstract S1641, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.

    2. Neelapu SS, et al. N Engl J Med. 2017 Dec 28;377(26):2531-2544.


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