Targeted therapy, immunotherapy may benefit patients with leptomeningeal metastases from melanoma

Patients with leptomeningeal metastases (LM) from melanoma have a poor prognosis, but treatment with targeted therapy and immune checkpoint inhibitors increased overall survival and resulted in long-term remission in a few patients, according to researchers.

The median survival for 21 patients who were treated with a BRAF inhibitor and/or ipilimumab was 21.7 weeks (range 2 to 235+ weeks); 24.9 weeks for treatment including a BRAF inhibitor (with and without a MEK inhibitor); 15.8 weeks for treatment including ipilimumab; and 4.3 weeks for radiotherapy (RT) only (Annals of Oncology 2016 March 8. doi: 10.1093/annonc/mdw134).

“A remarkable and encouraging new finding in our study is the long-term survival of patients who were treated with targeted treatment or immunotherapy. Moreover, the median survival of 22 weeks following these new therapies compares favorably to reported results of [intrathecal] chemotherapy for LM from melanoma,” wrote Dr. Marnix Geukes Foppen of Netherlands Cancer Institute, Amsterdam, and colleagues.

The retrospective analysis evaluated 39 consecutive patients treated at the Netherlands Cancer Institute during 2010-2015. Because of rapid disease progression or poor performance status, 14 patients did not receive treatment for LM, and their median survival was 2.9 weeks. Among 25 patients who were treated for LM, 15 received cranial or spinal RT and 21 received systemic therapy, and the median survival was 16.9 weeks.

Patients with performance status of 2 or 3 had worse survival than did those with performance status of 0 or 1 (3.6 vs. 18.8 weeks, P less than .001), and treatment did not significantly improve survival in this group (median 1.9 weeks for untreated vs. 3.9 weeks for treated). Patients with increased serum levels of lactate dehydrogenase and/or S100B had poorer survival compared with patients with normal levels.

The investigators noted that ipilimumab increases anti-tumor T cell activation in the lymph nodes, and activated T cells can cross the blood-brain or blood-CSF barrier. RT combined with ipilimumab may increase responses. Among 10 patients whose treatment included ipilimumab, median survival was 15.8 weeks; median survival was 47 weeks for ipilimumab with RT, and 6 weeks for ipilimumab without RT. A patient who had lymph node and lung metastasis, and LM without brain metastasis, was treated with whole brain RT and four cycles of ipilimumab, resulting in a complete radiological and clinical remission beyond 54 months.

Combining systemic targeted therapy and immunotherapy may result in long-term remissions, according the investigators.

“Especially in LM patients with a good performance score and low serum LDH and S100B levels these treatment options should be considered,” they wrote.

Patients with leptomeningeal metastases (LM) from melanoma have a poor prognosis, but treatment with targeted therapy and immune checkpoint inhibitors increased overall survival and resulted in long-term remission in a few patients, according to researchers.

The median survival for 21 patients who were treated with a BRAF inhibitor and/or ipilimumab was 21.7 weeks (range 2 to 235+ weeks); 24.9 weeks for treatment including a BRAF inhibitor (with and without a MEK inhibitor); 15.8 weeks for treatment including ipilimumab; and 4.3 weeks for radiotherapy (RT) only (Annals of Oncology 2016 March 8. doi: 10.1093/annonc/mdw134).

“A remarkable and encouraging new finding in our study is the long-term survival of patients who were treated with targeted treatment or immunotherapy. Moreover, the median survival of 22 weeks following these new therapies compares favorably to reported results of [intrathecal] chemotherapy for LM from melanoma,” wrote Dr. Marnix Geukes Foppen of Netherlands Cancer Institute, Amsterdam, and colleagues.

The retrospective analysis evaluated 39 consecutive patients treated at the Netherlands Cancer Institute during 2010-2015. Because of rapid disease progression or poor performance status, 14 patients did not receive treatment for LM, and their median survival was 2.9 weeks. Among 25 patients who were treated for LM, 15 received cranial or spinal RT and 21 received systemic therapy, and the median survival was 16.9 weeks.

Patients with performance status of 2 or 3 had worse survival than did those with performance status of 0 or 1 (3.6 vs. 18.8 weeks, P less than .001), and treatment did not significantly improve survival in this group (median 1.9 weeks for untreated vs. 3.9 weeks for treated). Patients with increased serum levels of lactate dehydrogenase and/or S100B had poorer survival compared with patients with normal levels.

The investigators noted that ipilimumab increases anti-tumor T cell activation in the lymph nodes, and activated T cells can cross the blood-brain or blood-CSF barrier. RT combined with ipilimumab may increase responses. Among 10 patients whose treatment included ipilimumab, median survival was 15.8 weeks; median survival was 47 weeks for ipilimumab with RT, and 6 weeks for ipilimumab without RT. A patient who had lymph node and lung metastasis, and LM without brain metastasis, was treated with whole brain RT and four cycles of ipilimumab, resulting in a complete radiological and clinical remission beyond 54 months.

Combining systemic targeted therapy and immunotherapy may result in long-term remissions, according the investigators.

“Especially in LM patients with a good performance score and low serum LDH and S100B levels these treatment options should be considered,” they wrote.

Patients with leptomeningeal metastases (LM) from melanoma have a poor prognosis, but treatment with targeted therapy and immune checkpoint inhibitors increased overall survival and resulted in long-term remission in a few patients, according to researchers.

The median survival for 21 patients who were treated with a BRAF inhibitor and/or ipilimumab was 21.7 weeks (range 2 to 235+ weeks); 24.9 weeks for treatment including a BRAF inhibitor (with and without a MEK inhibitor); 15.8 weeks for treatment including ipilimumab; and 4.3 weeks for radiotherapy (RT) only (Annals of Oncology 2016 March 8. doi: 10.1093/annonc/mdw134).

“A remarkable and encouraging new finding in our study is the long-term survival of patients who were treated with targeted treatment or immunotherapy. Moreover, the median survival of 22 weeks following these new therapies compares favorably to reported results of [intrathecal] chemotherapy for LM from melanoma,” wrote Dr. Marnix Geukes Foppen of Netherlands Cancer Institute, Amsterdam, and colleagues.

The retrospective analysis evaluated 39 consecutive patients treated at the Netherlands Cancer Institute during 2010-2015. Because of rapid disease progression or poor performance status, 14 patients did not receive treatment for LM, and their median survival was 2.9 weeks. Among 25 patients who were treated for LM, 15 received cranial or spinal RT and 21 received systemic therapy, and the median survival was 16.9 weeks.

Patients with performance status of 2 or 3 had worse survival than did those with performance status of 0 or 1 (3.6 vs. 18.8 weeks, P less than .001), and treatment did not significantly improve survival in this group (median 1.9 weeks for untreated vs. 3.9 weeks for treated). Patients with increased serum levels of lactate dehydrogenase and/or S100B had poorer survival compared with patients with normal levels.

The investigators noted that ipilimumab increases anti-tumor T cell activation in the lymph nodes, and activated T cells can cross the blood-brain or blood-CSF barrier. RT combined with ipilimumab may increase responses. Among 10 patients whose treatment included ipilimumab, median survival was 15.8 weeks; median survival was 47 weeks for ipilimumab with RT, and 6 weeks for ipilimumab without RT. A patient who had lymph node and lung metastasis, and LM without brain metastasis, was treated with whole brain RT and four cycles of ipilimumab, resulting in a complete radiological and clinical remission beyond 54 months.

Combining systemic targeted therapy and immunotherapy may result in long-term remissions, according the investigators.

“Especially in LM patients with a good performance score and low serum LDH and S100B levels these treatment options should be considered,” they wrote.