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Case Report/Case Series |

Subcutaneous Veltuzumab, a Humanized Anti-CD20 Antibody, in the Treatment of Refractory Pemphigus Vulgaris ONLINE FIRST

Christoph T. Ellebrecht, MD1; Eun J. Choi, BS1; David M. Allman, PhD2; Donald E. Tsai, MD, PhD3; William A. Wegener, MD, PhD4; David M. Goldenberg, ScD, MD4; Aimee S. Payne, MD, PhD1
[+] Author Affiliations
1Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
2Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia
3Department of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
4Immunomedics Inc, Morris Plains, New Jersey
JAMA Dermatol. Published online August 13, 2014. doi:10.1001/jamadermatol.2014.1939
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Importance  B-cell depletion with the anti-CD20 antibody rituximab is highly effective for pemphigus vulgaris (PV) treatment. However, most patients experience relapse, and intravenous rituximab infusions are expensive. Therefore, cost-effective anti-CD20 therapies are desirable.

Observations  A compassionate-use investigational new drug protocol was approved to administer veltuzumab, a second-generation humanized anti-CD20 antibody, to a patient with refractory PV. Veltuzumab was administered as two 320-mg (188 mg/m2) subcutaneous doses 2 weeks apart, resulting in complete remission of disease off therapy. The disease relapsed 2 years after treatment. A second cycle of subcutaneous veltuzumab, using the same dosage regimen, again induced complete remission off therapy, which remained at 9 months. No serious adverse events occurred during 35 months of follow-up. Serum veltuzumab levels were 22 and 29 μg/mL 2 weeks after the first dose of each cycle, and the drug remained detectable in the serum for longer than 3 months. Relapse and response to veltuzumab generally correlated with desmoglein 3 enzyme-linked immunosorbent assay index values. Shortly after a relapse that occurred after a long-term remission, the patient demonstrated an elevated naive (CD19+CD27) to memory (CD19+CD27+) B-cell ratio of 19.5 and transitional (CD19+CD24+CD38+) B-cell frequency of 12.5%.

Conclusions and Relevance  Subcutaneous veltuzumab may be a safe, effective, and more economical alternative to intravenous rituximab for PV therapy. Clinical trials of subcutaneous veltuzumab for PV are warranted.

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Figure 1.
Evaluation of Clinical Course, Treatments, Pharmacokinetics, and Response to Therapy

A, Immunosuppressant dosages and clinical outcomes. CR, complete remission (minimal therapy); CROT, CR off therapy. B, Pharmacokinetic analysis. Serum veltuzumab levels were 22 and 23 μg/mL and 29 and 4 μg/mL when measured at 0.5 and 3.0 months after veltuzumab cycles 1 and 2, respectively. C, Modified (1:1500) desmoglein 3 enzyme-linked immunosorbent assay (ELISA), which correlates with relapse and remission before and after veltuzumab cycle 2. D, Serum tetanus toxoid IgG remained stable.

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Figure 2.
Immunophenotype of Repopulating B Cells 26 Months After the First Cycle of Veltuzumab Therapy

A, CD19+ peripheral blood B-cell depletion and repopulation during the second cycle of veltuzumab therapy. B-cell subsets were analyzed at 26 months, shortly after relapse from long-term remission. B, Long-term remission after the first cycle of veltuzumab correlates with the elevation of naive (CD19+CD27) compared with memory (CD19+CD27+) B-cell frequencies. C, Long-term remission after the first cycle of veltuzumab correlates with the high levels (12.5%) of transitional (CD19+CD24+CD38+) B cells, as previously described.2

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