Abstract OBJECTIVE To report a case with refractory NMDA encephalitis in comatose for 18 months, who was treated successfully with bortezomib. BACKGROUND Anti-NMDA encephalitis is a rare autoimmune encephalitis. Standard therapy include corticosteroid, IVIG or plasma exchange, cyclophosphamide, rituximab, and tumor removal. Refractory cases are very severe and often stay in ICU on ventilation for several months to years. Bortezomib for the treatment of refractory anti-NMDA receptor encephalitis was reported. We have applied the treatment to our refractory case and successfully woke up the patient. And we have followed up the patient for 3 years. METHODS Case report. RESULTS A 40 yo male was diagnosed as anti-NMDA encephalitis. Standard therapy was applied. After stabilization, the patient was eventually discharged to ICU at a long term care subacute hospital. The patient was brought back for more Rituxan or steroid or IVIG therapy. The condition had not improved at all. Eighteen months in comatose, the patient had worsening NMDA titer in CSF to 1:640. Decision was made to start bortezumib as reported with modification: 1.3 mg/m2 bortezomib were administered on days 1, 8, 11 and 14 and allowed two weeks off therapy. After first cycle, the patent started to talk first word “hurt.” After 6 cycles, the patient sat up and started riding bicycles for physical therapy. The NMDA titer in CSF was reduced to 1:40 at the end of 6 cycles. One year later, the patent stood up and ambulated with a walker. One and half year later, the patient walks without assistance and his speech and cognition have significantly improved with good communication with family members and staff. CONCLUSIONS Proteasome inhibitor bortezomib might be considered to be the third line therapy as early as possible if the first line and second line are ineffective to treat anti-NMDA receptor encephalitis.

Abstract

OBJECTIVE

To report a case with refractory NMDA encephalitis in comatose for 18 months, who was treated successfully with bortezomib.

BACKGROUND

Anti-NMDA encephalitis is a rare autoimmune encephalitis. Standard therapy include corticosteroid, IVIG or plasma exchange, cyclophosphamide, rituximab, and tumor removal. Refractory cases are very severe and often stay in ICU on ventilation for several months to years. Bortezomib for the treatment of refractory anti-NMDA receptor encephalitis was reported. We have applied the treatment to our refractory case and successfully woke up the patient. And we have followed up the patient for 3 years.

METHODS

Case report.

RESULTS

A 40 yo male was diagnosed as anti-NMDA encephalitis. Standard therapy was applied. After stabilization, the patient was eventually discharged to ICU at a long term care subacute hospital. The patient was brought back for more Rituxan or steroid or IVIG therapy. The condition had not improved at all. Eighteen months in comatose, the patient had worsening NMDA titer in CSF to 1:640. Decision was made to start bortezumib as reported with modification: 1.3 mg/m2 bortezomib were administered on days 1, 8, 11 and 14 and allowed two weeks off therapy. After first cycle, the patent started to talk first word “hurt.” After 6 cycles, the patient sat up and started riding bicycles for physical therapy. The NMDA titer in CSF was reduced to 1:40 at the end of 6 cycles. One year later, the patent stood up and ambulated with a walker. One and half year later, the patient walks without assistance and his speech and cognition have significantly improved with good communication with family members and staff.

CONCLUSIONS

Proteasome inhibitor bortezomib might be considered to be the third line therapy as early as possible if the first line and second line are ineffective to treat anti-NMDA receptor encephalitis.

Abstract Standard therapy for recurrent GBM is bevacizumab, a monoclonal VEGF inhibitor that targets tumor vascularization. The response to bevacizumab is transient and short-lived (4–6 months) after which patients typically develop progressive physical and mental debilitation culminating in death. ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor- cell lysates. The hypothesized action of ERC1671 is to potentiate the patients’ immune system against the tumor. Goals of this ongoing, phase 2 study are to to determine the safety and effectiveness (over-all survival) of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab at the time of GBM recurrence. To date 16 recurrent bevacizumab-naïve GBM patients have been randomized to ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab or Placebo + Bevacizumab. Median age is 56.5 (39–74), 5 patients (31%) are female, and average KPS is 83 (70–100). Thirteen patients are deceased and were unblinded at the time of further progression: 5 received vaccine, 7 received placebo, and 1 is non-evaluable due to discontinuation before completing 1 cycle. Median overall survival of the deceased patients treated with ERC1671 + Bevacizumab was 328 days (10.9 months), compared to 245 days (8.2 months) for patients treated with Placebo + Bevacizumab. While sparse, the data to date suggest pre-treatment and maximal CD4+T lymphocyte count in the peripheral blood correlate with OS more strongly in the ERC1671 group than in the placebo group. First clinical results for toxicity show no difference in the distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs in either group. The phase 2 randomized, double-blinded study is ongoing with the addition of 2 subsites.

Abstract Meningioma is the most common primary intracranial tumor in adults. Thorough majority of tumors are slow growing, many patients fail first-line treatments with surgery and/or radiation. Others are poor surgical candidates for definitive surgical resection due to their age, tumor location or associated medical comorbidities. Few targeted therapies and biologics for meningioma are studied, and they have limited efficacy. This study aims to assess the efficacy and safety of Sandostatin LAR as a potential treatment for recurrent, treatment resistant meningiomas. The retrospective chart review included patients over 18 years of age and diagnosed with meningioma who were administered Sandostatin LAR from 01/01/2010 until 06/01/2017 at the University of California, Irvine (UCI). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoint was assessing safety. There were 47 patients included in the chart review. The mean age was 64 years old and 69.6% were female. The mean KPS score was 80 (60-100). The majority of patients were diagnosed with WHO grade 1 meningioma (73.3%) compared to WHO grade 2 (11.1%) and WHO grade 3 (15.6%). Of the 47 patients, 14 experienced disease progression and 6 died. The mean overall survival times for grade 1, 2, and 3 were 4.5, 2.3, and 0.91 years respectively. Median time to progression for grade 1, 2, and 3 were 3.1, 2.3, and 0.20 years respectively. The most common AE was diarrhea which occurred in 19 out of 47 patients. Overall, Sandostatin LAR was well tolerated. This is the largest reported cohort of meningioma patients treated with Sandostatin LAR and it suggests that Sandostatin LAR can be an effective, well tolerated treatment for these patients.

Abstract ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor- cell lysates. The hypothesized action of ERC1671 is to potentiate the patients’ immune system against the tumor. Goals of this ongoing, phase 2 study are to determine the safety and effectiveness (overall survival) of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab at the time of GBM recurrence. To date 22 recurrent bevacizumab-naïve rGBM patients have been randomized to ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab or Placebo + Bevacizumab. Median age is 56.5 (33–74), 7 patients (32%) are female, and average KPS is 82.3 (70–100). Of the 22, two discontinued before completing one cycle of therapy and two remain on blinded treatment. Currently 18 patients are unblinded due to further progression: 8 were on vaccine and 10 on placebo. Five of those on placebo crossed to vaccine at progression. All but one of the 18 are now deceased. Median overall survival of unblinded patients randomized to ERC1671 + Bevacizumab (n = 8) is 264.5 days from the start of study treatment, compared to 182 days for those randomized to placebo + Bevacizumab who did not cross over (n = 5). Median overall survival of unblinded patients on vaccine at randomization or crossover is 328 days after first study treatment (n = 13). While sparse, the data to date suggest pre-treatment and maximal CD4+T lymphocyte count in the peripheral blood correlate with OS more strongly in the ERC1671 group than in the placebo group. First clinical results for toxicity show no difference in the distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs in either group. This phase 2 randomized, double-blinded study is ongoing, with the addition of one more site.