Results of a Phase II Trial of Brentuximab Vedotin for CD30⁺ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis

Abstract

Purpose Brentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30+ receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30+ cutaneous T-cell lymphomas. Patients and Methods Forty-eight patients with CD30+ lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days. Results Forty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sézary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (≥ 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy (n = 6), transaminitis (n = 1), and arthralgias and fatigue (n = 2). Conclusion Brentuximab vedotin is both active and well tolerated in cutaneous T-cell lymphoma and lymphomatoid papulosis, with an overall response rate of 73% and complete response rate of 35%.

Brentuximab vedotin in refractory or relapsed peripheral T-cell lymphomas: the French named patient program experience in 56 patients

“…As previously described, 1 the most common (>20%) adverse events emerging from treatment of any grade were peripheral neuhaematologica 2016; 101:e103 ropathy (n=20, 53%), cytopenia (anemia: n=19, 51%; neutropenia: n=15, 42%), thrombocytopenia (n=14, 37%) and infections (n=10, 29%). With respect to the clinico-pathological groups, patients with primary cutaneous lymphomas (n=18) (entities known to differ in their clinical presentation and outcome from systemic PTCL 7 ) had an ORR at the end of treatment of 72% and a median PFS of 9.4 months (95%CI: 6.2; NR), which is consistent with the previous results of the phase II studies published by Duvic et al and Kim et al 5,6 Patients with systemic ALCL (n=24) had a better ORR than patients with non-ALCL systemic PTCL (n=14), with an ORR at the end of treatment of 62% (n=15) and 21% (n=3), respectively (P=0.04) ( Table 2). Moreover, more than half of the patients with non-ALCL systemic PTCL rapidly progressed during the first two cycles of BV.…”

“…To date, four studies have already addressed this issue and failed to demonstrate any correlation between response to BV and the level of CD30 expression on tumor cells. 4,5,6,10 In the previous report on systemic non-ALCL PTCL, 4 more than 80% of the cases featured no or low levels of CD30 expression (<25% of CD30 + tumor cells), and as in our study, some patients with only a weak CD30 expression on tumor cells responded to BV, raising the question of the mechanism of BV action in these cases. However, the heterogeneity of CD30 expression in our population highlights the likelihood for better response for patients with strong CD30 expression by tumor cells.…”

“…Mathilde Lamarque, 1,2,3 Céline Bossard, 4 Adrien Contejean, 5,6 Pauline Brice, 6 Marie Parrens, 7 Steven Le Gouill, 8,9 Josette Brière, 10 Reda Bouabdallah, 11 …”

IPH4102, a Humanized KIR3DL2 Antibody with Potent Activity against Cutaneous T-cell Lymphoma

“…BV preliminary efficacy data in CTCL are encouraging, but somewhat less impressive than in HL and ALCL (12,13). Its safety profile in CTCL is similar in nature and frequency of adverse events to what was previously observed in other brentuximab-treated patient populations, with 60% of patients peripheral neuropathy, experiencing sometimes long lasting (13), attributed to the cytotoxic drug component of the ADC. Interestingly, these mAb-based therapies are all directed to receptors expressed on immune cells, and therefore display imperfect specificity in tumor targeting.…”

“…Finally, BV (Adcetris) is the second antibody-drug conjugate (ADC) ever approved by the FDA and the European Medicines Agency [for the treatment of r/r Hodgkin's lymphoma (HL) and systemic anaplastic large-cell lymphoma (ALCL)]. BV preliminary efficacy data in CTCL are encouraging, but somewhat less impressive than in HL and ALCL (12,13). Its safety profile in CTCL is similar in nature and frequency of adverse events to what was previously observed in other brentuximab-treated patient populations, with 60% of patients peripheral neuropathy, experiencing sometimes long lasting (13), attributed to the cytotoxic drug component of the ADC.…”