Dataset Information

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%.

SUBMITTER: Duvic M

PROVIDER: S-EPMC4737859 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceBrentuximab vedotin is a monomethyl auristatin E-conjugated monoclonal antibody directed against CD30. It represents a potential treatment for the CD30+ lymphoproliferative disorder lymphomatoid papulosis (LyP), which currently has no approved treatment.ObjectiveTo assess the efficacy and safety of brentuximab vedotin for the treatment of LyP.Design, setting, and participantsIn this study conducted at The University of Texas MD Anderson Cancer Center from May 10, 2011, to March 31, 2017, a total of 12 patients with LyP received brentuximab vedotin. All patients were 18 years or older with a diagnosis of LyP and were also required to have scarring, more than 10 lesions, or active lesions on the face, hands, or feet. Nine patients were enrolled in a physician-initiated, open-label, single-center, phase 2 clinical trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and LyP from 2011 to 2013. Three patients were later treated outside of the trial from 2013 to 2017. Five patients continued to be followed up as of March 2017.InterventionsIntravenous brentuximab vedotin 1.8 mg/kg infused over 30 minutes every 21 days.Main outcomes and measuresThe primary end point was the overall response rate. Complete response was defined as zero lesions, and partial response was defined as a 50% or greater reduction in lesion count from baseline. A relapse was defined as loss of partial response.ResultsAll 12 patients (8 men and 4 women; median age, 46 years) responded to brentuximab vedotin, and 7 exhibited a complete response. Time to response was 3 weeks in all patients. The median duration of response was 20 weeks (range, 6-103 weeks). For 5 patients who relapsed, the median time to relapse was 12 weeks (range, 6-41 weeks). One patient who relapsed was retreated and has remained in partial response for more than 23 months. Grade 1 to 2 neuropathy occurred in 10 patients but resolved in 5. Adverse events of grade 3 or higher were neutropenia (n = 2) and dizziness/vertigo (n = 1). Three patients withdrew owing to adverse events.Conclusions and relevanceBrentuximab vedotin is effective in treating LyP (overall response rate, 100%; complete response rate, 58%), but its use should be reserved for patients with truly severe and refractory LyP. More work is needed to optimize its dosing to minimize adverse events, such as peripheral neuropathy.Trial registrationclinicaltrials.gov Identifier: NCT01352520.

Project description:BACKGROUND:Primary cutaneous CD30+ lymphoproliferative disorders (CD30CLPD) are the second most common type of cutaneous T cell lymphoma (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Case reports and small patient series suggest an association of CD30CLPD with atopic disorders. However, the prevalence of atopy in patients with CD30CLPD in retrospective studies depends on patients' recall which is not always reliable. More objective criteria of atopy include evidence of skin reactivity to allergens (positive prick test) and evidence of allergen-specific IgE in serum. This study was undertaken to test the hypothesis that atopy is prevalent in patients with CD30CLPD using serologic criteria of allergen-specific IgE antibodies to aeroallergens and Staphylococcal aureus enterotoxin superantigens (SSAgs). METHODS:We tested serum samples of CD30CLPD for common IgE-specific airborne allergens with the Phadiatop test, which if positive, is regarded as serologic evidence of atopy in adults. Sera were also tested for IgE antibodies reactive to three Staphylococcal enterotoxins with superantigenic properties (SSAg-IgE). Control sera were obtained from adult subjects evaluated for rhino-sinusitis and a negative Phadiatop test. Patients' history of an atopic disorder was obtained by retrospective chart review. FINDINGS:Nearly 50% of patients with the most common LyP types (A and C) had a positive Phadiatop test for allergic sensitization to common airborne allergens, and total serum IgE (IgE-t) was increased compared to non-atopic controls. At the IgE antibody concentration generally used to define serologic atopy (≥ 0.35 kUA/L), 8/31 (26%) samples of CD30CLPD and 7/28 (25%) samples of LyP were reactive to at least one SSAg-IgE compared to 3/52 (6%) control specimens (P = 0.016 and P = 0.028, respectively). TSST1-IgE was detected in 7 (23%) specimens of CD30CLPD, often together with SEB-IgE; SEA-IgE ≥ 0.35 kUA/L was not detected. For control specimens, TSST1-IgE exceeded the 0.35 kUA/L threshold in 3 (6%) specimens. CONCLUSIONS:Patients with LyP types A and C have serologic evidence of atopy against common airborne antigens and SSAgs when compared to control adult subjects who had rhino-sinusitis and a negative Phadiatop test for aero-IgEs. Serologic evidence of atopy exceeded that determined by LyP patients' personal history. The findings support our hypothesis that an atopic diathesis may contribute to the pathogenesis of the most common types of LyP (A and C).

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