Brentuximab Vedotin in the Treatment of Cutaneuous T Cell Lymphomas: A Multicenter, Retrospective, Case-Control Study from Italy
Authors: Morsia Erika , Grandi Vieri , Zizzari Annagiulia , Loseto Giacomo , Fava Paolo , Alberti Violetti Silvia , Pileri Alessandro , Broccoli Alessandro , Vitiello Paola , Sica Antonello , Nassi Luca , Di Riamondo Cosimo , Quaglino Pietro , Pimpinelli Nicola , Berti Emilio , Zinzani Pier Luigi , Rupoli Serena 
Published: December 2023

Brentuximab Vedotin (BV) is an anti-CD30 monoclonal antibody approved for relapsed/refractory CD30+ cutaneous T-cell lymphomas. The posology recommends its use until disease progression, unbearable toxicity, or completion of 16 cycles. A common side effect of BV is peripheral neuropathy (PN), which may lead to chronic complications and often leads to early treatment interruption.
To reduce long-term side effects, clinicians often choose to interrupt BV early when the patient shows an adequate response. However, it remains uncertain whether this approach effectively reduces the incidence of PN. Furthermore, it is unknown whether this reduction in cumulative dose negatively impacts the relapse-free interval (RFI) or the time to next treatment (TTNT).
This study aims to investigate whether a reduced BV treatment schedule is beneficial in terms of severe side effects compared to the standard schedule and to compare RFI and TTNT between the two schedules. The study was conducted retrospectively as a multicenter, observational case-control study.
Clinical and pathological data from 71 patients (44 males, median age 66 yeas) were analyzed. Various CTCLs subtypes were represented in the study population (43 had MF, 7 had folliculotropic MF, 10 had pc ALCL, 3 had PTCL-NOS, and 8 had SS).
The median follow-up duration was 525 days. Of the patients, 11 (15.4%) completed 16 cycles of BV, 21 (29.6%) stopped treatment due to disease progression (PD), 12(16.9%) experienced severe adverse events, 20 (28.1%) stopped treatment due to an adequate response based on the clinician's decision, the remaining patients were still under treatment at the time of data cut-off.
Out of the 71 patients, 20 developed PN, with 6 of them experiencing severe (G3) symptoms. At the last follow-up, 7 (35%) cases of PN had resolved, 8 were mild (G1), and 5 remained moderate (G2). No differences were observed in PN incidence or the number of infusions between patients who achieved an adequate clinical response and those who developed PN. No significant differences were observed in the median number of BV infusions between the groups.
Age at the time of the first infusion was the only variable associated with an increased risk of toxicity. However, no significant correlation was found between any variable and the incidence of PN.
The median RFI for patients receiving all 16 cycles was 882 days (95% CI 461, NA), compared to 357 days (95%CI 313, NA) for those who stopped BV after an adequate response, but this difference was not statistically significant (Pv=0.25). Similarly, the median TTNT in patients receiving all 16 cycles was 814 days (lower 95% CI = 458, upper NA), compared to 502 days in patients who stopped BV after achieving an adequate response (324, NA; pV=0.6).
In conclusion, based on the data analyzed, early interruption of BV after achieving an adequate response did not significantly reduce the incidence of severe adverse events or PN. Further data are required to determine if early interruption of BV negatively impacts patients' RFI or TTNT.