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Aligning with previous data, the drug combination was modestly effective in patients with large B-cell lymphoma pre- and post-CAR-T-cell therapy.
The combination of tafasitamab and lenalidomide in patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) who were previously treated with chimeric antigen receptor (CAR) T-cell therapy led to modest efficacy, with similar outcomes to other salvage treatments, though outcomes improved when disease progression occurred 6 months following CAR-T-cell therapy, according to data from a study published in Blood Advances.1
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In 2020, the FDA approved tafasitamab, a CD19-targeting monoclonal antibody, in combination with lenalidomide, an immunomodulatory treatment, for use in patients with LBCL. Studies have indicated the safety and effectiveness of the combination in patients with LBCL, including diffuse LBCL (DLBCL). In one study, 41.2% of patients with DLBCL had a complete response, and there were no concerning safety signals.2,3
However, data has emerged that suggests administering tafasitamab prior to anti-CD19 CAR T-cell therapy could lead to a delay in CD19 re-expression or result in a lessening of signal intensity.1
Importantly, it remains unknown whether exposure to one form of anti-CD19 therapy can compromise the effectiveness of another. To gain a better understanding, the investigators assessed the outcomes of patients with R/R LBCL treated with tafasitamab and lenalidomide (TL) as either a pre- or post-anti-CD19 CAR T-cell therapy in a French cohort.1
Co-primary end points were progression-free survival (PFS), overall survival (OS), and duration of response following treatment for the first progression post-CAR T-cell therapy. In the TL-post-CAR-T set, secondary end points included safety events, response rates, and outcomes according to CD19 status.1
Firstly, the TL-post-CAR-T set of patients was examined. In total, 52 patients were treated with tafasitamab-lenalidomide following their CAR T-cell infusions. At a median follow-up date of 7 months, the PFS and OS since the first treatment for progression was 3 (95% CI: 1.9-4.2) and 4.7 (3-5.6) months, respectively. Interestingly, when tafasitamab-lenalidomide was initiated >6 months following CAR T-cell treatment, PFS increased.1
The drug combination was also compared to other treatments as an initial therapy for progression after CAR T-cell therapy. Outcomes between 43 patients treated with the regimen were compared to 354 control patients treated with different agents, such as chemotherapy or bispecific antibodies. It was found that PFS and OS did not significantly differ between the groups.1
Moving to an analysis of TL-pre-CAR T-cell therapy, 15 patients were analyzed. Four patients had a positive CD19 status, while 1 patient did not, and 10 others were not tested. At a median follow-up point of 2.8 months, 6-month PFS rate was 20.1%, while OS rate following CAR-T infusion was 58.2%.1
Trial Name: French Register Of Patients With Hemopathy Eligible For CAR-T Cell Treatment (DESCAR-T)
ClinicalTrials.gov ID: NCT04328298
Sponsor: The Lymphoma Academic Research Organisation
Estimated Study Completion Date: December 19, 2038
Results from this trial, DESCAR-T (NCT04328298), come from the largest cohort to date of patients treated either before or after CAR T-cell infusion with either commercial anti-CD19 therapy or the tafasitamab and lenalidomide combination. When comparing to the prior study analyzing DLBCL patients, the results with the drug combination are similar across these disease states.1,3
The study authors wrote that their results confirmed the poor prognosis of patients who relapsed following CAR T-cell therapy, regardless of the treatment received. They noted that targeting an epitope other than CD19 using a CD3xCD20 bispecific antibody could be an interesting approach to treating the disease, though they agreed that more thorough analyses are necessary.1
In regard to the cohort of patients administered TL pre-CAR T therapy, the investigators felt that the limited study sample size and short follow-up period prevent definitive conclusions from being drawn from the data. They noted that patients in the cohort presented high-risk characteristics, which could partly explain the poor outcomes observed.1
Lastly, the investigators discussed the role of CD19 as a potential biomarker of the response to the different treatment options. Ultimately, they were unable to sufficiently study the issue because the staining is largely not performed in practice in a real-life setting. In France, checking CD19 positivity is not required to prescribe CAR T-cell, which contributed to the low amount of data on CD19 status.1
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