This year’s annual meeting of The Connective Tissue Oncology Society brought new insights on intimal sarcoma. Four studies in a featured session at the meeting examined both current and novel treatments for this rare and aggressive cancer, and emphasized the need for new therapies.

Anthracycline-based regimens as preferred first-line therapies

Anthracycline-based regimens were the preferred first-line therapies used in 83 adults with intimal sarcomas in a retrospective study of data from the World Sarcoma Network, reported by Anna Maria Frezza, MD, of the, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and her colleagues. The researchers described the experience with anthracycline-based regimens as well as gemcitabine-based regimens and pazopanib among MDM2-positive patients with intimal sarcomas treated at 16 sarcoma reference centers in Europe, the United States, and Japan. Their findings speak to the need for new active drugs, which they said should target the MDM2 and CDK4 overexpression seen in patients with this rare sarcoma.Of the 83 patients studied, nearly all (76 patients) initially received an anthracycline-based regimen. Gemcitabine-based regimens were used in 29 patients and pazopanib in 10 patients; 20 of the 39 patients received more than one treatment.

Anthracycline-based regimens were associated with a 12-month progression-free survival rate of 38% in 76 patients with intimal sarcomas. All of the 76 patients received anthracycline regimens as their initial systemic therapy; 27 were treated for localized disease with a curative intent and the remaining 49 had advanced disease. The researchers also noted that anthracycline regimens were safely used in 22 patients with cardiac intimal sarcomas, as none of them died of cardiotoxicity.

Based on RECIST 1.1 measures, the overall response rate was 37% in 57 evaluable patients: 3 patients had a complete response, 18 had a partial response, 27 had stable disease, and 9 had progressive disease. For those with localized disease, the median time to progression was 14 months, and overall survival time was 51. For patients with advanced disease, the median time to progression was 8 months and overall survival was 22 months.

Outcomes were less favorable when patients were treated with gemcitabine regimens or pazopanib. In most of these cases, however, patients were either on their second (gemcitabine) or third (pazopanib) lines of therapy.

In the gemcitabine group, 2 patients were treated for localized disease with curative intent and 27 for advanced disease. Of 28 evaluable patients, best response was partial remission in 3, stable disease in 8, and progressive disease in 17. In the 27 patients with advanced disease, the median progression free survival time was 3 months and overall survival was 13 months.

All 10 patients in the pazopanib group had advanced disease and had undergone a median of two prior lines of therapy. One patient had a partial remission, 3 had stable disease, and 6 had progressive disease. The median progression free survival was 4 months and median overall survival was 12 months.

Rarest of the rare: Primary malignant sarcoma of the heart

Luke Smith, of the School of Clinical Medicine, University of Cambridge, U.K., detailed the experience of 28 patients diagnosed with sarcomas of the heart or great vessels at the university’s Royal Papworth Hospital and Addenbrooke’s Hospital between 2000 and 2018.

Based on this retrospective review, surgery offers the best chance for long-term survival for these patients, who would otherwise experience progressive heart failure and die. Adjuvant chemotherapy and radiation therapy might be able to extend their survival and improve symptomatic relief, he said, but these outcomes have not been prospectively studied.

Typically, the patients in this series, 20 with pulmonary artery sarcoma and 8 with cardiac sarcoma, presented with symptoms mimicking heart failure, pulmonary hypertension, or thromboembolic disease. Nearly all, 24 patients reported breathlessness. Eight patients had chest pain or tightness, 6 had cough, 6 had peripheral edema, 6 had constitutional symptoms, 3 had hemoptysis, and 1 had a TIA. Only 1 patient had a seriously impaired left ventricular ejection fraction of less than 30%. LVEF was normal at 55% or more in 16 patients, and moderately impaired at 30% or more in 10 patients.

Median overall survival was 17 months. The 19 patients who underwent surgical resection of their primary tumor survived much longer than the 10 patients who did not--median overall survival of 20 months vs. 9 months--but this finding may simply reflect more advanced disease in patients with inoperable disease. There were 3 perioperative deaths among the 19 patients who underwent surgery: 14 with pulmonary artery sarcomas had pulmonary endarterectomy and 4 with cardiac sarcomas underwent resection or maximal debulking of their tumors.

Based on the retrospective study, adjuvant chemotherapy and radiation were safe and may lead to better outcomes for these patients. Active chemotherapy regimens in the palliative setting included paclitaxel (angiosarcoma) and anthracycline ± ifosfamide.

Nine patients received post-surgical chemotherapy, and after completion five also had radiotherapy. The 3 cardiac sarcoma patients who had surgical resection with curative intent were treated with adjuvant ifosfamide-based chemotherapy (with close monitoring of fluid balance), and showed no evidence of disease on last follow-ups. One patient received post-operative paclitaxel following maximal debulking of a cardiac angiosarcoma.

Post-surgical anthracycline with and without ifosfamide were used in patients with pulmonary artery sarcomas with no clinical cardiotoxicity. Although the median overall survival for patients who received post-operative chemo- and radio-therapy was 28 months and the median overall survival with surgery alone was 9 months, the difference was not statistically significant.

In the palliative setting, partial responses were observed with paclitaxel and anthracycline (including liposomal doxorubicin) in patients with cardiac angiosarcoma. For pulmonary artery intimal sarcomas, partial responses were achieved with anthracycline with and without ifosfamide. Radiotherapy provided good local control.

The longest surviving pulmonary artery sarcoma patient, at 103 months, had pulmonary artery endarterectomy, followed by adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later and was treated with radiofrequency ablation. The longest surviving cardiac sarcoma patient, at 24 months, remains disease free. He had surgery to resect a high-grade undifferentiated sarcoma with involved margins, followed by adjuvant ifosfamide and radiotherapy to the right atrium.

Therapeutically exploitable genetic aberrations in intimal sarcomas

Imatinib and olaratumab might prove to be therapeutic approaches for some patients with intimal sarcomas, based on a retrospective evaluation of genetic aberrations in 11 patients with intimal sarcomas, Jason Roszik, PhD, MBA, reported at the meeting.

Dr. Roszik and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, analyzed information on 11 patients with intimal sarcomas in the American Association for Cancer Research (AACR) project, Genomics Evidence Neoplasia Information Exchange (GENIE). Sampling was taken from the primary tumor in 8 patients and from the metastatic site in the other 3.

MDM2 amplifications were seen in 8 of 10 patients with available copy number alterations. Amplifications in the CDK pathway were present in 5, PDGFRA gain was seen in 4, and CDKN2A copy number loss was present in 3. Mutations that could be targeted with drugs included ALK, ATM/ATR, PTCH1 and PDGFRB, he said.

Unique genomic rearrangement events included PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion tumor, and PDGFRB mutations in both fusion-positive cases.

The researchers also drew on the published findings of whole-exome sequencing and array-comparative genomic hybridization from an autopsy case of cardiac intimal sarcoma (Virchows Arch. 2017 Sep;471(3):423-428). That study identified concurrent PDGFRA amplification and PDGFRB mutation.

The researchers additionally examined clinical trial enrollments and could find no patient with intimal sarcoma among 406 sarcoma enrolled patients. Intimal sarcomas were not eligible for any clinical trial given the location of the tumors in major blood vessels.

“The somatic mutations and DNA copy number alterations in the PDGFR pathway relevant to the pathogenesis and potential targeted therapy of cardiac intimal sarcoma may be targeted by imatinib or olaratumab. Inclusion of such rare tumors in targeted therapy basket trials with a waiver for inclusion criteria is warranted,” Dr. Roszik and his colleagues concluded in the abstract of their presentation.

The promise of combination therapy

The “largest experience using multimodality therapy with proton based local therapy” for sarcomas involving the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries was reported by Yen-Lin E. Chen, MD, and her colleagues at Massachusetts General Hospital, Boston.

They examined an institutional sarcoma data repository of 13,950 patients and found 37 patients with sarcomas arising from the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries. These included 9 with unclassified pleomorphic sarcoma/malignant fibrous histiocytoma, 8 with angiosarcoma, 4 with spindle cell sarcoma, 4 with sarcoma not otherwise specified, 3 with leiomyosarcoma, 2 with osteosarcoma, 2 with Ewing sarcoma, and 1 each with chondrosarcoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, synovial sarcoma, and intimal sarcoma.

Two-thirds of the patients had induction chemotherapy with or without maintenance therapy. Adriamycin, ifosfamide, and taxol therapies were most common. Two-thirds received proton based radiotherapy. Of the 23 patients who underwent resection, 11 were R2 (macroscopic positive margins), 3 were R1 (microscopic positive margins), and 9 were R0 (clear margins).

The 1-year overall survival rate was 64%, which fell to 37% at 3 years and to 28% at 5 years. Median survival was 28 months, twice that typically seen in the literature, Dr. Chen said.

For patients receiving proton based radiotherapy to a median dose of 64.8 GyRBE (range 63-72 GyRBE, 3 with additional intraoperative electrons), local failure free survivals were 80%, 64%, and 52% at 1, 3, and 5 years, respectively. For patients who did not receive radiotherapy, local failure free survival rates were 13%, 10%, 10%, respectively.

Overall, the 1, 3, and 5 year metastatic free survival rates were 25%, 14%, and 14%.

Survival rate was significantly better for patients with tumors smaller than 5 cm ( P =0.036), those over 40 years old ( P =0.028), those able to have surgery ( P =0.011), and those with non-angiosarcoma histologies ( P = 0.002).

This year’s annual meeting of The Connective Tissue Oncology Society brought new insights on intimal sarcoma. Four studies in a featured session at the meeting examined both current and novel treatments for this rare and aggressive cancer, and emphasized the need for new therapies.

Anthracycline-based regimens as preferred first-line therapies

Anthracycline-based regimens were the preferred first-line therapies used in 83 adults with intimal sarcomas in a retrospective study of data from the World Sarcoma Network, reported by Anna Maria Frezza, MD, of the, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and her colleagues. The researchers described the experience with anthracycline-based regimens as well as gemcitabine-based regimens and pazopanib among MDM2-positive patients with intimal sarcomas treated at 16 sarcoma reference centers in Europe, the United States, and Japan. Their findings speak to the need for new active drugs, which they said should target the MDM2 and CDK4 overexpression seen in patients with this rare sarcoma.Of the 83 patients studied, nearly all (76 patients) initially received an anthracycline-based regimen. Gemcitabine-based regimens were used in 29 patients and pazopanib in 10 patients; 20 of the 39 patients received more than one treatment.

Anthracycline-based regimens were associated with a 12-month progression-free survival rate of 38% in 76 patients with intimal sarcomas. All of the 76 patients received anthracycline regimens as their initial systemic therapy; 27 were treated for localized disease with a curative intent and the remaining 49 had advanced disease. The researchers also noted that anthracycline regimens were safely used in 22 patients with cardiac intimal sarcomas, as none of them died of cardiotoxicity.

Based on RECIST 1.1 measures, the overall response rate was 37% in 57 evaluable patients: 3 patients had a complete response, 18 had a partial response, 27 had stable disease, and 9 had progressive disease. For those with localized disease, the median time to progression was 14 months, and overall survival time was 51. For patients with advanced disease, the median time to progression was 8 months and overall survival was 22 months.

Outcomes were less favorable when patients were treated with gemcitabine regimens or pazopanib. In most of these cases, however, patients were either on their second (gemcitabine) or third (pazopanib) lines of therapy.

In the gemcitabine group, 2 patients were treated for localized disease with curative intent and 27 for advanced disease. Of 28 evaluable patients, best response was partial remission in 3, stable disease in 8, and progressive disease in 17. In the 27 patients with advanced disease, the median progression free survival time was 3 months and overall survival was 13 months.

All 10 patients in the pazopanib group had advanced disease and had undergone a median of two prior lines of therapy. One patient had a partial remission, 3 had stable disease, and 6 had progressive disease. The median progression free survival was 4 months and median overall survival was 12 months.

Rarest of the rare: Primary malignant sarcoma of the heart

Luke Smith, of the School of Clinical Medicine, University of Cambridge, U.K., detailed the experience of 28 patients diagnosed with sarcomas of the heart or great vessels at the university’s Royal Papworth Hospital and Addenbrooke’s Hospital between 2000 and 2018.

Based on this retrospective review, surgery offers the best chance for long-term survival for these patients, who would otherwise experience progressive heart failure and die. Adjuvant chemotherapy and radiation therapy might be able to extend their survival and improve symptomatic relief, he said, but these outcomes have not been prospectively studied.

Typically, the patients in this series, 20 with pulmonary artery sarcoma and 8 with cardiac sarcoma, presented with symptoms mimicking heart failure, pulmonary hypertension, or thromboembolic disease. Nearly all, 24 patients reported breathlessness. Eight patients had chest pain or tightness, 6 had cough, 6 had peripheral edema, 6 had constitutional symptoms, 3 had hemoptysis, and 1 had a TIA. Only 1 patient had a seriously impaired left ventricular ejection fraction of less than 30%. LVEF was normal at 55% or more in 16 patients, and moderately impaired at 30% or more in 10 patients.

Median overall survival was 17 months. The 19 patients who underwent surgical resection of their primary tumor survived much longer than the 10 patients who did not--median overall survival of 20 months vs. 9 months--but this finding may simply reflect more advanced disease in patients with inoperable disease. There were 3 perioperative deaths among the 19 patients who underwent surgery: 14 with pulmonary artery sarcomas had pulmonary endarterectomy and 4 with cardiac sarcomas underwent resection or maximal debulking of their tumors.

Based on the retrospective study, adjuvant chemotherapy and radiation were safe and may lead to better outcomes for these patients. Active chemotherapy regimens in the palliative setting included paclitaxel (angiosarcoma) and anthracycline ± ifosfamide.

Nine patients received post-surgical chemotherapy, and after completion five also had radiotherapy. The 3 cardiac sarcoma patients who had surgical resection with curative intent were treated with adjuvant ifosfamide-based chemotherapy (with close monitoring of fluid balance), and showed no evidence of disease on last follow-ups. One patient received post-operative paclitaxel following maximal debulking of a cardiac angiosarcoma.

Post-surgical anthracycline with and without ifosfamide were used in patients with pulmonary artery sarcomas with no clinical cardiotoxicity. Although the median overall survival for patients who received post-operative chemo- and radio-therapy was 28 months and the median overall survival with surgery alone was 9 months, the difference was not statistically significant.

In the palliative setting, partial responses were observed with paclitaxel and anthracycline (including liposomal doxorubicin) in patients with cardiac angiosarcoma. For pulmonary artery intimal sarcomas, partial responses were achieved with anthracycline with and without ifosfamide. Radiotherapy provided good local control.

The longest surviving pulmonary artery sarcoma patient, at 103 months, had pulmonary artery endarterectomy, followed by adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later and was treated with radiofrequency ablation. The longest surviving cardiac sarcoma patient, at 24 months, remains disease free. He had surgery to resect a high-grade undifferentiated sarcoma with involved margins, followed by adjuvant ifosfamide and radiotherapy to the right atrium.

Therapeutically exploitable genetic aberrations in intimal sarcomas

Imatinib and olaratumab might prove to be therapeutic approaches for some patients with intimal sarcomas, based on a retrospective evaluation of genetic aberrations in 11 patients with intimal sarcomas, Jason Roszik, PhD, MBA, reported at the meeting.

Dr. Roszik and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, analyzed information on 11 patients with intimal sarcomas in the American Association for Cancer Research (AACR) project, Genomics Evidence Neoplasia Information Exchange (GENIE). Sampling was taken from the primary tumor in 8 patients and from the metastatic site in the other 3.

MDM2 amplifications were seen in 8 of 10 patients with available copy number alterations. Amplifications in the CDK pathway were present in 5, PDGFRA gain was seen in 4, and CDKN2A copy number loss was present in 3. Mutations that could be targeted with drugs included ALK, ATM/ATR, PTCH1 and PDGFRB, he said.

Unique genomic rearrangement events included PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion tumor, and PDGFRB mutations in both fusion-positive cases.

The researchers also drew on the published findings of whole-exome sequencing and array-comparative genomic hybridization from an autopsy case of cardiac intimal sarcoma (Virchows Arch. 2017 Sep;471(3):423-428). That study identified concurrent PDGFRA amplification and PDGFRB mutation.

The researchers additionally examined clinical trial enrollments and could find no patient with intimal sarcoma among 406 sarcoma enrolled patients. Intimal sarcomas were not eligible for any clinical trial given the location of the tumors in major blood vessels.

“The somatic mutations and DNA copy number alterations in the PDGFR pathway relevant to the pathogenesis and potential targeted therapy of cardiac intimal sarcoma may be targeted by imatinib or olaratumab. Inclusion of such rare tumors in targeted therapy basket trials with a waiver for inclusion criteria is warranted,” Dr. Roszik and his colleagues concluded in the abstract of their presentation.

The promise of combination therapy

The “largest experience using multimodality therapy with proton based local therapy” for sarcomas involving the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries was reported by Yen-Lin E. Chen, MD, and her colleagues at Massachusetts General Hospital, Boston.

They examined an institutional sarcoma data repository of 13,950 patients and found 37 patients with sarcomas arising from the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries. These included 9 with unclassified pleomorphic sarcoma/malignant fibrous histiocytoma, 8 with angiosarcoma, 4 with spindle cell sarcoma, 4 with sarcoma not otherwise specified, 3 with leiomyosarcoma, 2 with osteosarcoma, 2 with Ewing sarcoma, and 1 each with chondrosarcoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, synovial sarcoma, and intimal sarcoma.

Two-thirds of the patients had induction chemotherapy with or without maintenance therapy. Adriamycin, ifosfamide, and taxol therapies were most common. Two-thirds received proton based radiotherapy. Of the 23 patients who underwent resection, 11 were R2 (macroscopic positive margins), 3 were R1 (microscopic positive margins), and 9 were R0 (clear margins).

The 1-year overall survival rate was 64%, which fell to 37% at 3 years and to 28% at 5 years. Median survival was 28 months, twice that typically seen in the literature, Dr. Chen said.

For patients receiving proton based radiotherapy to a median dose of 64.8 GyRBE (range 63-72 GyRBE, 3 with additional intraoperative electrons), local failure free survivals were 80%, 64%, and 52% at 1, 3, and 5 years, respectively. For patients who did not receive radiotherapy, local failure free survival rates were 13%, 10%, 10%, respectively.

Overall, the 1, 3, and 5 year metastatic free survival rates were 25%, 14%, and 14%.

Survival rate was significantly better for patients with tumors smaller than 5 cm ( P =0.036), those over 40 years old ( P =0.028), those able to have surgery ( P =0.011), and those with non-angiosarcoma histologies ( P = 0.002).

This year’s annual meeting of The Connective Tissue Oncology Society brought new insights on intimal sarcoma. Four studies in a featured session at the meeting examined both current and novel treatments for this rare and aggressive cancer, and emphasized the need for new therapies.

Anthracycline-based regimens as preferred first-line therapies

Anthracycline-based regimens were the preferred first-line therapies used in 83 adults with intimal sarcomas in a retrospective study of data from the World Sarcoma Network, reported by Anna Maria Frezza, MD, of the, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and her colleagues. The researchers described the experience with anthracycline-based regimens as well as gemcitabine-based regimens and pazopanib among MDM2-positive patients with intimal sarcomas treated at 16 sarcoma reference centers in Europe, the United States, and Japan. Their findings speak to the need for new active drugs, which they said should target the MDM2 and CDK4 overexpression seen in patients with this rare sarcoma.Of the 83 patients studied, nearly all (76 patients) initially received an anthracycline-based regimen. Gemcitabine-based regimens were used in 29 patients and pazopanib in 10 patients; 20 of the 39 patients received more than one treatment.

Anthracycline-based regimens were associated with a 12-month progression-free survival rate of 38% in 76 patients with intimal sarcomas. All of the 76 patients received anthracycline regimens as their initial systemic therapy; 27 were treated for localized disease with a curative intent and the remaining 49 had advanced disease. The researchers also noted that anthracycline regimens were safely used in 22 patients with cardiac intimal sarcomas, as none of them died of cardiotoxicity.

Based on RECIST 1.1 measures, the overall response rate was 37% in 57 evaluable patients: 3 patients had a complete response, 18 had a partial response, 27 had stable disease, and 9 had progressive disease. For those with localized disease, the median time to progression was 14 months, and overall survival time was 51. For patients with advanced disease, the median time to progression was 8 months and overall survival was 22 months.

Outcomes were less favorable when patients were treated with gemcitabine regimens or pazopanib. In most of these cases, however, patients were either on their second (gemcitabine) or third (pazopanib) lines of therapy.

In the gemcitabine group, 2 patients were treated for localized disease with curative intent and 27 for advanced disease. Of 28 evaluable patients, best response was partial remission in 3, stable disease in 8, and progressive disease in 17. In the 27 patients with advanced disease, the median progression free survival time was 3 months and overall survival was 13 months.

All 10 patients in the pazopanib group had advanced disease and had undergone a median of two prior lines of therapy. One patient had a partial remission, 3 had stable disease, and 6 had progressive disease. The median progression free survival was 4 months and median overall survival was 12 months.

Rarest of the rare: Primary malignant sarcoma of the heart

Luke Smith, of the School of Clinical Medicine, University of Cambridge, U.K., detailed the experience of 28 patients diagnosed with sarcomas of the heart or great vessels at the university’s Royal Papworth Hospital and Addenbrooke’s Hospital between 2000 and 2018.

Based on this retrospective review, surgery offers the best chance for long-term survival for these patients, who would otherwise experience progressive heart failure and die. Adjuvant chemotherapy and radiation therapy might be able to extend their survival and improve symptomatic relief, he said, but these outcomes have not been prospectively studied.

Typically, the patients in this series, 20 with pulmonary artery sarcoma and 8 with cardiac sarcoma, presented with symptoms mimicking heart failure, pulmonary hypertension, or thromboembolic disease. Nearly all, 24 patients reported breathlessness. Eight patients had chest pain or tightness, 6 had cough, 6 had peripheral edema, 6 had constitutional symptoms, 3 had hemoptysis, and 1 had a TIA. Only 1 patient had a seriously impaired left ventricular ejection fraction of less than 30%. LVEF was normal at 55% or more in 16 patients, and moderately impaired at 30% or more in 10 patients.

Median overall survival was 17 months. The 19 patients who underwent surgical resection of their primary tumor survived much longer than the 10 patients who did not--median overall survival of 20 months vs. 9 months--but this finding may simply reflect more advanced disease in patients with inoperable disease. There were 3 perioperative deaths among the 19 patients who underwent surgery: 14 with pulmonary artery sarcomas had pulmonary endarterectomy and 4 with cardiac sarcomas underwent resection or maximal debulking of their tumors.

Based on the retrospective study, adjuvant chemotherapy and radiation were safe and may lead to better outcomes for these patients. Active chemotherapy regimens in the palliative setting included paclitaxel (angiosarcoma) and anthracycline ± ifosfamide.

Nine patients received post-surgical chemotherapy, and after completion five also had radiotherapy. The 3 cardiac sarcoma patients who had surgical resection with curative intent were treated with adjuvant ifosfamide-based chemotherapy (with close monitoring of fluid balance), and showed no evidence of disease on last follow-ups. One patient received post-operative paclitaxel following maximal debulking of a cardiac angiosarcoma.

Post-surgical anthracycline with and without ifosfamide were used in patients with pulmonary artery sarcomas with no clinical cardiotoxicity. Although the median overall survival for patients who received post-operative chemo- and radio-therapy was 28 months and the median overall survival with surgery alone was 9 months, the difference was not statistically significant.

In the palliative setting, partial responses were observed with paclitaxel and anthracycline (including liposomal doxorubicin) in patients with cardiac angiosarcoma. For pulmonary artery intimal sarcomas, partial responses were achieved with anthracycline with and without ifosfamide. Radiotherapy provided good local control.

The longest surviving pulmonary artery sarcoma patient, at 103 months, had pulmonary artery endarterectomy, followed by adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later and was treated with radiofrequency ablation. The longest surviving cardiac sarcoma patient, at 24 months, remains disease free. He had surgery to resect a high-grade undifferentiated sarcoma with involved margins, followed by adjuvant ifosfamide and radiotherapy to the right atrium.

Therapeutically exploitable genetic aberrations in intimal sarcomas

Imatinib and olaratumab might prove to be therapeutic approaches for some patients with intimal sarcomas, based on a retrospective evaluation of genetic aberrations in 11 patients with intimal sarcomas, Jason Roszik, PhD, MBA, reported at the meeting.

Dr. Roszik and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, analyzed information on 11 patients with intimal sarcomas in the American Association for Cancer Research (AACR) project, Genomics Evidence Neoplasia Information Exchange (GENIE). Sampling was taken from the primary tumor in 8 patients and from the metastatic site in the other 3.

MDM2 amplifications were seen in 8 of 10 patients with available copy number alterations. Amplifications in the CDK pathway were present in 5, PDGFRA gain was seen in 4, and CDKN2A copy number loss was present in 3. Mutations that could be targeted with drugs included ALK, ATM/ATR, PTCH1 and PDGFRB, he said.

Unique genomic rearrangement events included PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion tumor, and PDGFRB mutations in both fusion-positive cases.

The researchers also drew on the published findings of whole-exome sequencing and array-comparative genomic hybridization from an autopsy case of cardiac intimal sarcoma (Virchows Arch. 2017 Sep;471(3):423-428). That study identified concurrent PDGFRA amplification and PDGFRB mutation.

The researchers additionally examined clinical trial enrollments and could find no patient with intimal sarcoma among 406 sarcoma enrolled patients. Intimal sarcomas were not eligible for any clinical trial given the location of the tumors in major blood vessels.

“The somatic mutations and DNA copy number alterations in the PDGFR pathway relevant to the pathogenesis and potential targeted therapy of cardiac intimal sarcoma may be targeted by imatinib or olaratumab. Inclusion of such rare tumors in targeted therapy basket trials with a waiver for inclusion criteria is warranted,” Dr. Roszik and his colleagues concluded in the abstract of their presentation.

The promise of combination therapy

The “largest experience using multimodality therapy with proton based local therapy” for sarcomas involving the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries was reported by Yen-Lin E. Chen, MD, and her colleagues at Massachusetts General Hospital, Boston.

They examined an institutional sarcoma data repository of 13,950 patients and found 37 patients with sarcomas arising from the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries. These included 9 with unclassified pleomorphic sarcoma/malignant fibrous histiocytoma, 8 with angiosarcoma, 4 with spindle cell sarcoma, 4 with sarcoma not otherwise specified, 3 with leiomyosarcoma, 2 with osteosarcoma, 2 with Ewing sarcoma, and 1 each with chondrosarcoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, synovial sarcoma, and intimal sarcoma.

Two-thirds of the patients had induction chemotherapy with or without maintenance therapy. Adriamycin, ifosfamide, and taxol therapies were most common. Two-thirds received proton based radiotherapy. Of the 23 patients who underwent resection, 11 were R2 (macroscopic positive margins), 3 were R1 (microscopic positive margins), and 9 were R0 (clear margins).

The 1-year overall survival rate was 64%, which fell to 37% at 3 years and to 28% at 5 years. Median survival was 28 months, twice that typically seen in the literature, Dr. Chen said.

For patients receiving proton based radiotherapy to a median dose of 64.8 GyRBE (range 63-72 GyRBE, 3 with additional intraoperative electrons), local failure free survivals were 80%, 64%, and 52% at 1, 3, and 5 years, respectively. For patients who did not receive radiotherapy, local failure free survival rates were 13%, 10%, 10%, respectively.

Overall, the 1, 3, and 5 year metastatic free survival rates were 25%, 14%, and 14%.

Survival rate was significantly better for patients with tumors smaller than 5 cm ( P =0.036), those over 40 years old ( P =0.028), those able to have surgery ( P =0.011), and those with non-angiosarcoma histologies ( P = 0.002).

MONTREAL – Enhanced and prolonged rhythm monitoring for atrial fibrillation in patients with a recent acute ischemic stroke did not find more arrhythmias, it just found them faster, in a randomized study with 398 German patients.

Mitchel L. Zoler/MDedge News

“Prolonged and enhanced monitoring identified atrial fibrillation cases that otherwise were detected years later,” Rolf Wachter, MD, said at the World Stroke Congress. Enhanced and prolonged monitoring (EPM) “should be considered for all stroke patients, regardless of the suspected stroke etiology, if detection of atrial fibrillation is of clinical relevance,” said Dr. Wachter, a cardiologist and professor at the University Clinic in Leipzig, Germany.

Based on 3-year follow-up of patients enrolled in the FIND-AF study, which randomized patients within 7 days of an acute ischemic stroke to either EPM for atrial fibrillation (AF) or standard work-up and follow-up, Dr. Wachter calculated that every six such patients who underwent EMP for AF yielded one added patient who could receive anticoagulant prophylaxis for 1 year, an effect that should result in fewer incident strokes and deaths. The data he reported showed after 3 years a “favorable trend” toward fewer strokes and deaths among patients who underwent EPM.

FIND-AF RANDOMISED (A Prospective, Randomised, Controlled Study to Determine the Detection of Atrial Fibrillation by Prolonged and Enhanced Holter Monitoring as Compared to Usual Care in Stroke Patients) ran at four German centers during May 2013–August 2014. It enrolled 398 patients aged 60 years or older within 7 days of an acute ischemic stroke who were in sinus rhythm and had no AF history. Enrolled patients could have any type of suspected stroke etiology, but the study excluded patients with severe stenosis in their ipsilateral carotid or intracranial arteries. The study randomized patients to received EPM or a standard work-up. The “enhanced” part of EPM meant review of Holter monitor recordings by a single, dedicated core laboratory. The “prolonged” part meant routinely screening patients for an atrial arrhythmia using a Holter monitor worn for 10 consecutive days on three occasions: at entry into the study, 3 months later, and 6 months later.

The study’s primary endpoint was the number of patients diagnosed with AF after 6 months, which was 27 of 200 patients (13.5%) in the EPM arm and 9 of 198 patients (4.5%) in the control arm, a statistically significant difference, Dr. Wachter and his associates reported in Lancet Neurology (2017 Apr 1;16[4]:282-90).

The additional 30 months of follow-up included in the new report by Dr. Wachter resulted in identification of 3 more patients with AF in the EPM group and 13 more patients in the control arm, which brought the total number of patients with AF identified over 3 years to 30 in the EPM group (15%), and 22 in the control group (11%), a difference that was not statistically significant. In other words, both approaches found roughly the same percentage of patients with AF, but the EPM method found them quicker.

During the extended 36-month follow-up, 12 patients in the EPM group had an ischemic stroke and 9 patients died, with a combined stroke and death rate of about 8%. In the control group, 19 patients had a second ischemic stroke and 13 died, with a combined rate of about 15%. A statistical test of the difference between the combined stroke and death rates in these two groups produced a P value of .08.

FIND-AF was funded by Boehringer Ingelheim. Dr. Wachter has been a speaker on behalf of and has received research funding from Boehringer Ingelheim, and he has also been a speaker on behalf of Bayer, BMS/Pfizer, and Daiichi Sankyo.

mzoler@mdedge.com

SOURCE: Wachter R et al. World Stroke Congress, Abstract.

MONTREAL – Enhanced and prolonged rhythm monitoring for atrial fibrillation in patients with a recent acute ischemic stroke did not find more arrhythmias, it just found them faster, in a randomized study with 398 German patients.

Mitchel L. Zoler/MDedge News

“Prolonged and enhanced monitoring identified atrial fibrillation cases that otherwise were detected years later,” Rolf Wachter, MD, said at the World Stroke Congress. Enhanced and prolonged monitoring (EPM) “should be considered for all stroke patients, regardless of the suspected stroke etiology, if detection of atrial fibrillation is of clinical relevance,” said Dr. Wachter, a cardiologist and professor at the University Clinic in Leipzig, Germany.

Based on 3-year follow-up of patients enrolled in the FIND-AF study, which randomized patients within 7 days of an acute ischemic stroke to either EPM for atrial fibrillation (AF) or standard work-up and follow-up, Dr. Wachter calculated that every six such patients who underwent EMP for AF yielded one added patient who could receive anticoagulant prophylaxis for 1 year, an effect that should result in fewer incident strokes and deaths. The data he reported showed after 3 years a “favorable trend” toward fewer strokes and deaths among patients who underwent EPM.

FIND-AF RANDOMISED (A Prospective, Randomised, Controlled Study to Determine the Detection of Atrial Fibrillation by Prolonged and Enhanced Holter Monitoring as Compared to Usual Care in Stroke Patients) ran at four German centers during May 2013–August 2014. It enrolled 398 patients aged 60 years or older within 7 days of an acute ischemic stroke who were in sinus rhythm and had no AF history. Enrolled patients could have any type of suspected stroke etiology, but the study excluded patients with severe stenosis in their ipsilateral carotid or intracranial arteries. The study randomized patients to received EPM or a standard work-up. The “enhanced” part of EPM meant review of Holter monitor recordings by a single, dedicated core laboratory. The “prolonged” part meant routinely screening patients for an atrial arrhythmia using a Holter monitor worn for 10 consecutive days on three occasions: at entry into the study, 3 months later, and 6 months later.

The study’s primary endpoint was the number of patients diagnosed with AF after 6 months, which was 27 of 200 patients (13.5%) in the EPM arm and 9 of 198 patients (4.5%) in the control arm, a statistically significant difference, Dr. Wachter and his associates reported in Lancet Neurology (2017 Apr 1;16[4]:282-90).

The additional 30 months of follow-up included in the new report by Dr. Wachter resulted in identification of 3 more patients with AF in the EPM group and 13 more patients in the control arm, which brought the total number of patients with AF identified over 3 years to 30 in the EPM group (15%), and 22 in the control group (11%), a difference that was not statistically significant. In other words, both approaches found roughly the same percentage of patients with AF, but the EPM method found them quicker.

During the extended 36-month follow-up, 12 patients in the EPM group had an ischemic stroke and 9 patients died, with a combined stroke and death rate of about 8%. In the control group, 19 patients had a second ischemic stroke and 13 died, with a combined rate of about 15%. A statistical test of the difference between the combined stroke and death rates in these two groups produced a P value of .08.

FIND-AF was funded by Boehringer Ingelheim. Dr. Wachter has been a speaker on behalf of and has received research funding from Boehringer Ingelheim, and he has also been a speaker on behalf of Bayer, BMS/Pfizer, and Daiichi Sankyo.

mzoler@mdedge.com

SOURCE: Wachter R et al. World Stroke Congress, Abstract.

MONTREAL – Enhanced and prolonged rhythm monitoring for atrial fibrillation in patients with a recent acute ischemic stroke did not find more arrhythmias, it just found them faster, in a randomized study with 398 German patients.

Mitchel L. Zoler/MDedge News

“Prolonged and enhanced monitoring identified atrial fibrillation cases that otherwise were detected years later,” Rolf Wachter, MD, said at the World Stroke Congress. Enhanced and prolonged monitoring (EPM) “should be considered for all stroke patients, regardless of the suspected stroke etiology, if detection of atrial fibrillation is of clinical relevance,” said Dr. Wachter, a cardiologist and professor at the University Clinic in Leipzig, Germany.

Based on 3-year follow-up of patients enrolled in the FIND-AF study, which randomized patients within 7 days of an acute ischemic stroke to either EPM for atrial fibrillation (AF) or standard work-up and follow-up, Dr. Wachter calculated that every six such patients who underwent EMP for AF yielded one added patient who could receive anticoagulant prophylaxis for 1 year, an effect that should result in fewer incident strokes and deaths. The data he reported showed after 3 years a “favorable trend” toward fewer strokes and deaths among patients who underwent EPM.

FIND-AF RANDOMISED (A Prospective, Randomised, Controlled Study to Determine the Detection of Atrial Fibrillation by Prolonged and Enhanced Holter Monitoring as Compared to Usual Care in Stroke Patients) ran at four German centers during May 2013–August 2014. It enrolled 398 patients aged 60 years or older within 7 days of an acute ischemic stroke who were in sinus rhythm and had no AF history. Enrolled patients could have any type of suspected stroke etiology, but the study excluded patients with severe stenosis in their ipsilateral carotid or intracranial arteries. The study randomized patients to received EPM or a standard work-up. The “enhanced” part of EPM meant review of Holter monitor recordings by a single, dedicated core laboratory. The “prolonged” part meant routinely screening patients for an atrial arrhythmia using a Holter monitor worn for 10 consecutive days on three occasions: at entry into the study, 3 months later, and 6 months later.

The study’s primary endpoint was the number of patients diagnosed with AF after 6 months, which was 27 of 200 patients (13.5%) in the EPM arm and 9 of 198 patients (4.5%) in the control arm, a statistically significant difference, Dr. Wachter and his associates reported in Lancet Neurology (2017 Apr 1;16[4]:282-90).

The additional 30 months of follow-up included in the new report by Dr. Wachter resulted in identification of 3 more patients with AF in the EPM group and 13 more patients in the control arm, which brought the total number of patients with AF identified over 3 years to 30 in the EPM group (15%), and 22 in the control group (11%), a difference that was not statistically significant. In other words, both approaches found roughly the same percentage of patients with AF, but the EPM method found them quicker.

During the extended 36-month follow-up, 12 patients in the EPM group had an ischemic stroke and 9 patients died, with a combined stroke and death rate of about 8%. In the control group, 19 patients had a second ischemic stroke and 13 died, with a combined rate of about 15%. A statistical test of the difference between the combined stroke and death rates in these two groups produced a P value of .08.

FIND-AF was funded by Boehringer Ingelheim. Dr. Wachter has been a speaker on behalf of and has received research funding from Boehringer Ingelheim, and he has also been a speaker on behalf of Bayer, BMS/Pfizer, and Daiichi Sankyo.

mzoler@mdedge.com

SOURCE: Wachter R et al. World Stroke Congress, Abstract.

The Food and Drug Administration has approved romiplostim (Nplate) for pediatric patients aged 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The FDA based the approval on two trials in pediatric patients 1 year and older with ITP for at least 6 months duration.

In the first trial, 62 patients were randomized 2:1 to receive romiplostim or placebo; differences in durable platelet response, overall platelet response, and duration of response were all statistically significant, with P values less than .05.

Durable platelet response (at least 6 weekly platelet counts greater than or equal to 50 × 10⁹/L during weeks 18 through 25 of treatment) was achieved in 22 patients (52%) who received romiplostim and 2 (10%) who received placebo. Overall platelet response was achieved in 30 (71%) and 4 (20%) patients, respectively. Patients who received romiplostim had platelet counts greater than or equal to 50 x 10⁹/L for a median of 12 weeks, compared with 1 week in patients who received placebo, the FDA said in a statement.

In the second randomized trial, 22 patients were randomized 3:1 to receive romiplostim or placebo; 15 patients in the romiplostim arm achieved a platelet count greater than or equal to 50 x 10⁹/L for 2 consecutive weeks and an increase in platelet count of greater than or equal to 20 × 10⁹/L above baseline for 2 consecutive weeks during the treatment period (88%; 95% confidence interval, 64%-99%), compared with 0 patients in the placebo arm.

The most common adverse reactions observed in children receiving romiplostim include contusion, upper respiratory tract infection, and oropharyngeal pain.

The recommended initial romiplostim dose for pediatric patients is 1 mcg/kg based on actual body weight and administered as a weekly subcutaneous injection. Dose should be adjusted in increments of 1 mcg/kg until the patient achieves a platelet count greater than or equal to 50 x 10⁹/L. Body weight should be reassessed every 12 weeks, according to the FDA announcement.

lnikolaides@mdedge.com

The Food and Drug Administration has approved romiplostim (Nplate) for pediatric patients aged 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The FDA based the approval on two trials in pediatric patients 1 year and older with ITP for at least 6 months duration.

In the first trial, 62 patients were randomized 2:1 to receive romiplostim or placebo; differences in durable platelet response, overall platelet response, and duration of response were all statistically significant, with P values less than .05.

Durable platelet response (at least 6 weekly platelet counts greater than or equal to 50 × 10⁹/L during weeks 18 through 25 of treatment) was achieved in 22 patients (52%) who received romiplostim and 2 (10%) who received placebo. Overall platelet response was achieved in 30 (71%) and 4 (20%) patients, respectively. Patients who received romiplostim had platelet counts greater than or equal to 50 x 10⁹/L for a median of 12 weeks, compared with 1 week in patients who received placebo, the FDA said in a statement.

In the second randomized trial, 22 patients were randomized 3:1 to receive romiplostim or placebo; 15 patients in the romiplostim arm achieved a platelet count greater than or equal to 50 x 10⁹/L for 2 consecutive weeks and an increase in platelet count of greater than or equal to 20 × 10⁹/L above baseline for 2 consecutive weeks during the treatment period (88%; 95% confidence interval, 64%-99%), compared with 0 patients in the placebo arm.

The most common adverse reactions observed in children receiving romiplostim include contusion, upper respiratory tract infection, and oropharyngeal pain.

The recommended initial romiplostim dose for pediatric patients is 1 mcg/kg based on actual body weight and administered as a weekly subcutaneous injection. Dose should be adjusted in increments of 1 mcg/kg until the patient achieves a platelet count greater than or equal to 50 x 10⁹/L. Body weight should be reassessed every 12 weeks, according to the FDA announcement.

lnikolaides@mdedge.com

The Food and Drug Administration has approved romiplostim (Nplate) for pediatric patients aged 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The FDA based the approval on two trials in pediatric patients 1 year and older with ITP for at least 6 months duration.

In the first trial, 62 patients were randomized 2:1 to receive romiplostim or placebo; differences in durable platelet response, overall platelet response, and duration of response were all statistically significant, with P values less than .05.

Durable platelet response (at least 6 weekly platelet counts greater than or equal to 50 × 10⁹/L during weeks 18 through 25 of treatment) was achieved in 22 patients (52%) who received romiplostim and 2 (10%) who received placebo. Overall platelet response was achieved in 30 (71%) and 4 (20%) patients, respectively. Patients who received romiplostim had platelet counts greater than or equal to 50 x 10⁹/L for a median of 12 weeks, compared with 1 week in patients who received placebo, the FDA said in a statement.

In the second randomized trial, 22 patients were randomized 3:1 to receive romiplostim or placebo; 15 patients in the romiplostim arm achieved a platelet count greater than or equal to 50 x 10⁹/L for 2 consecutive weeks and an increase in platelet count of greater than or equal to 20 × 10⁹/L above baseline for 2 consecutive weeks during the treatment period (88%; 95% confidence interval, 64%-99%), compared with 0 patients in the placebo arm.

The most common adverse reactions observed in children receiving romiplostim include contusion, upper respiratory tract infection, and oropharyngeal pain.

The recommended initial romiplostim dose for pediatric patients is 1 mcg/kg based on actual body weight and administered as a weekly subcutaneous injection. Dose should be adjusted in increments of 1 mcg/kg until the patient achieves a platelet count greater than or equal to 50 x 10⁹/L. Body weight should be reassessed every 12 weeks, according to the FDA announcement.

lnikolaides@mdedge.com

A group of internists is suing the American Board of Internal Medicine over its maintenance of certification. Also today, drug test results should not dictate treatment, duodenoscopes contain more bacteria than expected, and weight-loss medications may have a role following bariatric surgery.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

A group of internists is suing the American Board of Internal Medicine over its maintenance of certification. Also today, drug test results should not dictate treatment, duodenoscopes contain more bacteria than expected, and weight-loss medications may have a role following bariatric surgery.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

A group of internists is suing the American Board of Internal Medicine over its maintenance of certification. Also today, drug test results should not dictate treatment, duodenoscopes contain more bacteria than expected, and weight-loss medications may have a role following bariatric surgery.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Photo courtesy of ASH

SAN DIEGO—An update of the ZUMA-3 trial showed that KTE-X19—an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy—can induce high rates of undetectable minimal residual disease (MRD) and durable complete remissions (CRs) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

And this was particularly the case at the middle dose level of 1 x 10⁶ cells/kg.

William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, presented the update at the 2018 ASH Annual Meeting (abstract 897*).

Dr. Wierda explained that KTE-X19 is a new name for KTE-C19, also known as axicabtagene ciloleucel (Yescarta™), which is currently approved in the United States for the treatment of relapsed diffuse large B-cell lymphoma in adults and in Europe for diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma.

“This approval was based on the ZUMA-1 clinical trial,” he said, “which showed a 54% complete remission rate and 82% overall response rate with durable remissions.”

ZUMA-3 (NCT02614066) is a phase 1/2 study of KTE-X19—a CAR T cell with CD3ζ signaling and CD28 costimulatory domains—for relapsed or refractory adults with ALL.

Dr. Wierda presented the phase 1 data available at the cutoff of August 16.

Study design

Patients underwent leukapheresis to collect their T cells for production and received bridging therapy selected by the treating physician from several prespecified regimens to maintain disease control.

Conditioning chemotherapy included fludarabine at 25 mg/m² on days -4, -3, and -2 and cyclophosphamide at 900 mg/m² on day -2.

Patients received KTE-X19 on day 0. They were monitored and released from the hospital on day 7 or upon resolution of any toxicities.

The investigators assessed response, including bone marrow evaluation, on day 28, week 8, month 3, and every 3 months for the first year as well as every 6 months for the second year of follow-up.

The dose-finding portion of the trial initially enrolled three patients. They received a dose of 2 x 10⁶ CAR T cells/kg and were monitored for dose-limiting toxicities (DLTs).

If there were no DLTs in the first three patients, phase 2 could open or investigators could further expand the 2 x 10⁶ dose level or explore lower doses of the product (1 x 10⁶ cells/kg and 0.5 x 10⁶ cells/kg).

Investigators defined DLTs as:

• KTE-X19-related events in the first 28 days, including grade 4 hematologic toxicity lasting more than 30 days and not attributable to ALL
• Grade 3 nonhematologic toxicities lasting more than 7 days
• Grade 4 nonhematologic toxicities regardless of duration, excluding grade 4 cytokine release syndrome (CRS) events lasting 7 days or less
• Neurologic events that resolve to grade 1 in 2 weeks or to baseline within 4 weeks.

Dr. Wierda said no DLTs occurred among the first 3 patients treated, and all dose levels were explored in phase 1.

Patients

As of the cutoff date, 54 patients were enrolled, confirmed eligible, and underwent leukapheresis. Six patients did not receive conditioning, three patients received conditioning but not KTE-X19, and one patient withdrew from the study after the first failed production of CAR T cells.

So 44 patients received KTE-X19. Six patients received the highest dose of CAR T cells (2 x 10⁶/kg), 22 received the middle dose (1 x 10⁶/kg), and 16 received the lowest dose (0.5 x 10⁶/kg).

The patients’ median age was 46 (range, 18 – 77). Almost half (48%) were male, and 68% had three or more prior treatment regimens. Forty-one percent had prior blinatumomab, and 14% had prior inotuzumab.

Patients had a median bone marrow blast percentage of 59% (n=44; range, 5% - 100%) at screening and 70% (n=40; range, 0 – 97%) prior to conditioning but after bridging therapy.

The safety analysis included all 44 treated patients, and the efficacy analysis included 36 patients.

“[T]he follow-up period was too short from dosing for the most recently treated eight patients,” Dr Wierda explained.

The median follow-up was 15.1 months for the 36 efficacy-evaluable patients.

Safety

All patients had a treatment-emergent adverse events (TEAEs), with 75% having grade 3/4 events.

Grade 5 TEAEs included three due to progressive disease, three due to infections, and one stroke 6 weeks after infusion.

Two patients died of KTE-X19-related AEs. One patient in the 2 x 10⁶ dose group had multiorgan failure secondary to CRS on study day 6. The other patient, in the 0.5 x 10⁶ dose group, had a stroke after infusion in the context of CRS and neurologic events (NEs) on day 7.

Investigators detected a higher incidence of grade 3 and greater CRS for the six patients treated at the highest dose. Half developed CRS of grade 3 or higher, compared with 18% in the 1 x 10⁶ dose cohort and 19% in the 0.5 x 10⁶ dose cohort.

Grade 3 or higher NEs were more common than CRS. The lowest incidence occurred in the lowest dose cohort, at 25%, compared with 45% in the 1 x 10⁶ dose cohort and 50% in the 2 x 10⁶ dose cohort.

Due to the incidence of grade 3 and greater NEs observed in the 1 x 10⁶ dose cohort, investigators revised the management guidelines for AEs. The revisions included using tocilizumab only for CRS—and not for NEs—and initiating steroids for grade 2 NEs instead of waiting for grade 3.

Eight patients were treated under the revised recommendations, and the incidence of grade 3 NEs was 13%, with no grade 4 or 5 NEs.

“This compared favorably with the 14 patients treated at the same dose level but prior to these changes," Dr. Wierda said.

In comparison, 57% developed grade 3 NEs and 7% grade 4 with the original AE management protocol.

The incidence of grade 3 CRS remained low, with no CRS events of grade 4 or greater with the revised recommendations.

Efficacy

The best overall response in the 36 efficacy-evaluable patients was 69% CR and CR with incomplete hematologic recovery (CRi).

Seventy-five percent of these patients had undetectable MRD in the bone marrow at 10^-4 sensitivity at 3 months of follow-up.

All patients in the 1 x 10⁶ dose cohort (n=14) responded. Ninety-three percent achieved a CR/CRi, 7% had a partial response, and all had undetectable MRD in the bone marrow.

The median duration of response was 12.9 months in the 1 x 10⁶ cohort. This was the dose selected for the phase 2 trial, which is now enrolling patients.

ZUMA-3 was sponsored by Kite, a Gilead Company.

Dr. Wierda disclosed research funding from AbbVie and Genentech. 

* Data in the abstract differ from the presentation.

Photo courtesy of ASH

SAN DIEGO—An update of the ZUMA-3 trial showed that KTE-X19—an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy—can induce high rates of undetectable minimal residual disease (MRD) and durable complete remissions (CRs) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

And this was particularly the case at the middle dose level of 1 x 10⁶ cells/kg.

William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, presented the update at the 2018 ASH Annual Meeting (abstract 897*).

Dr. Wierda explained that KTE-X19 is a new name for KTE-C19, also known as axicabtagene ciloleucel (Yescarta™), which is currently approved in the United States for the treatment of relapsed diffuse large B-cell lymphoma in adults and in Europe for diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma.

“This approval was based on the ZUMA-1 clinical trial,” he said, “which showed a 54% complete remission rate and 82% overall response rate with durable remissions.”

ZUMA-3 (NCT02614066) is a phase 1/2 study of KTE-X19—a CAR T cell with CD3ζ signaling and CD28 costimulatory domains—for relapsed or refractory adults with ALL.

Dr. Wierda presented the phase 1 data available at the cutoff of August 16.

Study design

Patients underwent leukapheresis to collect their T cells for production and received bridging therapy selected by the treating physician from several prespecified regimens to maintain disease control.

Conditioning chemotherapy included fludarabine at 25 mg/m² on days -4, -3, and -2 and cyclophosphamide at 900 mg/m² on day -2.

Patients received KTE-X19 on day 0. They were monitored and released from the hospital on day 7 or upon resolution of any toxicities.

The investigators assessed response, including bone marrow evaluation, on day 28, week 8, month 3, and every 3 months for the first year as well as every 6 months for the second year of follow-up.

The dose-finding portion of the trial initially enrolled three patients. They received a dose of 2 x 10⁶ CAR T cells/kg and were monitored for dose-limiting toxicities (DLTs).

If there were no DLTs in the first three patients, phase 2 could open or investigators could further expand the 2 x 10⁶ dose level or explore lower doses of the product (1 x 10⁶ cells/kg and 0.5 x 10⁶ cells/kg).

Investigators defined DLTs as:

• KTE-X19-related events in the first 28 days, including grade 4 hematologic toxicity lasting more than 30 days and not attributable to ALL
• Grade 3 nonhematologic toxicities lasting more than 7 days
• Grade 4 nonhematologic toxicities regardless of duration, excluding grade 4 cytokine release syndrome (CRS) events lasting 7 days or less
• Neurologic events that resolve to grade 1 in 2 weeks or to baseline within 4 weeks.

Dr. Wierda said no DLTs occurred among the first 3 patients treated, and all dose levels were explored in phase 1.

Patients

As of the cutoff date, 54 patients were enrolled, confirmed eligible, and underwent leukapheresis. Six patients did not receive conditioning, three patients received conditioning but not KTE-X19, and one patient withdrew from the study after the first failed production of CAR T cells.

So 44 patients received KTE-X19. Six patients received the highest dose of CAR T cells (2 x 10⁶/kg), 22 received the middle dose (1 x 10⁶/kg), and 16 received the lowest dose (0.5 x 10⁶/kg).

The patients’ median age was 46 (range, 18 – 77). Almost half (48%) were male, and 68% had three or more prior treatment regimens. Forty-one percent had prior blinatumomab, and 14% had prior inotuzumab.

Patients had a median bone marrow blast percentage of 59% (n=44; range, 5% - 100%) at screening and 70% (n=40; range, 0 – 97%) prior to conditioning but after bridging therapy.

The safety analysis included all 44 treated patients, and the efficacy analysis included 36 patients.

“[T]he follow-up period was too short from dosing for the most recently treated eight patients,” Dr Wierda explained.

The median follow-up was 15.1 months for the 36 efficacy-evaluable patients.

Safety

All patients had a treatment-emergent adverse events (TEAEs), with 75% having grade 3/4 events.

Grade 5 TEAEs included three due to progressive disease, three due to infections, and one stroke 6 weeks after infusion.

Two patients died of KTE-X19-related AEs. One patient in the 2 x 10⁶ dose group had multiorgan failure secondary to CRS on study day 6. The other patient, in the 0.5 x 10⁶ dose group, had a stroke after infusion in the context of CRS and neurologic events (NEs) on day 7.

Investigators detected a higher incidence of grade 3 and greater CRS for the six patients treated at the highest dose. Half developed CRS of grade 3 or higher, compared with 18% in the 1 x 10⁶ dose cohort and 19% in the 0.5 x 10⁶ dose cohort.

Grade 3 or higher NEs were more common than CRS. The lowest incidence occurred in the lowest dose cohort, at 25%, compared with 45% in the 1 x 10⁶ dose cohort and 50% in the 2 x 10⁶ dose cohort.

Due to the incidence of grade 3 and greater NEs observed in the 1 x 10⁶ dose cohort, investigators revised the management guidelines for AEs. The revisions included using tocilizumab only for CRS—and not for NEs—and initiating steroids for grade 2 NEs instead of waiting for grade 3.

Eight patients were treated under the revised recommendations, and the incidence of grade 3 NEs was 13%, with no grade 4 or 5 NEs.

“This compared favorably with the 14 patients treated at the same dose level but prior to these changes," Dr. Wierda said.

In comparison, 57% developed grade 3 NEs and 7% grade 4 with the original AE management protocol.

The incidence of grade 3 CRS remained low, with no CRS events of grade 4 or greater with the revised recommendations.

Efficacy

The best overall response in the 36 efficacy-evaluable patients was 69% CR and CR with incomplete hematologic recovery (CRi).

Seventy-five percent of these patients had undetectable MRD in the bone marrow at 10^-4 sensitivity at 3 months of follow-up.

All patients in the 1 x 10⁶ dose cohort (n=14) responded. Ninety-three percent achieved a CR/CRi, 7% had a partial response, and all had undetectable MRD in the bone marrow.

The median duration of response was 12.9 months in the 1 x 10⁶ cohort. This was the dose selected for the phase 2 trial, which is now enrolling patients.

ZUMA-3 was sponsored by Kite, a Gilead Company.

Dr. Wierda disclosed research funding from AbbVie and Genentech. 

* Data in the abstract differ from the presentation.

Photo courtesy of ASH

SAN DIEGO—An update of the ZUMA-3 trial showed that KTE-X19—an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy—can induce high rates of undetectable minimal residual disease (MRD) and durable complete remissions (CRs) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

And this was particularly the case at the middle dose level of 1 x 10⁶ cells/kg.

William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, presented the update at the 2018 ASH Annual Meeting (abstract 897*).

Dr. Wierda explained that KTE-X19 is a new name for KTE-C19, also known as axicabtagene ciloleucel (Yescarta™), which is currently approved in the United States for the treatment of relapsed diffuse large B-cell lymphoma in adults and in Europe for diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma.

“This approval was based on the ZUMA-1 clinical trial,” he said, “which showed a 54% complete remission rate and 82% overall response rate with durable remissions.”

ZUMA-3 (NCT02614066) is a phase 1/2 study of KTE-X19—a CAR T cell with CD3ζ signaling and CD28 costimulatory domains—for relapsed or refractory adults with ALL.

Dr. Wierda presented the phase 1 data available at the cutoff of August 16.

Study design

Patients underwent leukapheresis to collect their T cells for production and received bridging therapy selected by the treating physician from several prespecified regimens to maintain disease control.

Conditioning chemotherapy included fludarabine at 25 mg/m² on days -4, -3, and -2 and cyclophosphamide at 900 mg/m² on day -2.

Patients received KTE-X19 on day 0. They were monitored and released from the hospital on day 7 or upon resolution of any toxicities.

The investigators assessed response, including bone marrow evaluation, on day 28, week 8, month 3, and every 3 months for the first year as well as every 6 months for the second year of follow-up.

The dose-finding portion of the trial initially enrolled three patients. They received a dose of 2 x 10⁶ CAR T cells/kg and were monitored for dose-limiting toxicities (DLTs).

If there were no DLTs in the first three patients, phase 2 could open or investigators could further expand the 2 x 10⁶ dose level or explore lower doses of the product (1 x 10⁶ cells/kg and 0.5 x 10⁶ cells/kg).

Investigators defined DLTs as:

• KTE-X19-related events in the first 28 days, including grade 4 hematologic toxicity lasting more than 30 days and not attributable to ALL
• Grade 3 nonhematologic toxicities lasting more than 7 days
• Grade 4 nonhematologic toxicities regardless of duration, excluding grade 4 cytokine release syndrome (CRS) events lasting 7 days or less
• Neurologic events that resolve to grade 1 in 2 weeks or to baseline within 4 weeks.

Dr. Wierda said no DLTs occurred among the first 3 patients treated, and all dose levels were explored in phase 1.

Patients

As of the cutoff date, 54 patients were enrolled, confirmed eligible, and underwent leukapheresis. Six patients did not receive conditioning, three patients received conditioning but not KTE-X19, and one patient withdrew from the study after the first failed production of CAR T cells.

So 44 patients received KTE-X19. Six patients received the highest dose of CAR T cells (2 x 10⁶/kg), 22 received the middle dose (1 x 10⁶/kg), and 16 received the lowest dose (0.5 x 10⁶/kg).

The patients’ median age was 46 (range, 18 – 77). Almost half (48%) were male, and 68% had three or more prior treatment regimens. Forty-one percent had prior blinatumomab, and 14% had prior inotuzumab.

Patients had a median bone marrow blast percentage of 59% (n=44; range, 5% - 100%) at screening and 70% (n=40; range, 0 – 97%) prior to conditioning but after bridging therapy.

The safety analysis included all 44 treated patients, and the efficacy analysis included 36 patients.

“[T]he follow-up period was too short from dosing for the most recently treated eight patients,” Dr Wierda explained.

The median follow-up was 15.1 months for the 36 efficacy-evaluable patients.

Safety

All patients had a treatment-emergent adverse events (TEAEs), with 75% having grade 3/4 events.

Grade 5 TEAEs included three due to progressive disease, three due to infections, and one stroke 6 weeks after infusion.

Two patients died of KTE-X19-related AEs. One patient in the 2 x 10⁶ dose group had multiorgan failure secondary to CRS on study day 6. The other patient, in the 0.5 x 10⁶ dose group, had a stroke after infusion in the context of CRS and neurologic events (NEs) on day 7.

Investigators detected a higher incidence of grade 3 and greater CRS for the six patients treated at the highest dose. Half developed CRS of grade 3 or higher, compared with 18% in the 1 x 10⁶ dose cohort and 19% in the 0.5 x 10⁶ dose cohort.

Grade 3 or higher NEs were more common than CRS. The lowest incidence occurred in the lowest dose cohort, at 25%, compared with 45% in the 1 x 10⁶ dose cohort and 50% in the 2 x 10⁶ dose cohort.

Due to the incidence of grade 3 and greater NEs observed in the 1 x 10⁶ dose cohort, investigators revised the management guidelines for AEs. The revisions included using tocilizumab only for CRS—and not for NEs—and initiating steroids for grade 2 NEs instead of waiting for grade 3.

Eight patients were treated under the revised recommendations, and the incidence of grade 3 NEs was 13%, with no grade 4 or 5 NEs.

“This compared favorably with the 14 patients treated at the same dose level but prior to these changes," Dr. Wierda said.

In comparison, 57% developed grade 3 NEs and 7% grade 4 with the original AE management protocol.

The incidence of grade 3 CRS remained low, with no CRS events of grade 4 or greater with the revised recommendations.

Efficacy

The best overall response in the 36 efficacy-evaluable patients was 69% CR and CR with incomplete hematologic recovery (CRi).

Seventy-five percent of these patients had undetectable MRD in the bone marrow at 10^-4 sensitivity at 3 months of follow-up.

All patients in the 1 x 10⁶ dose cohort (n=14) responded. Ninety-three percent achieved a CR/CRi, 7% had a partial response, and all had undetectable MRD in the bone marrow.

The median duration of response was 12.9 months in the 1 x 10⁶ cohort. This was the dose selected for the phase 2 trial, which is now enrolling patients.

ZUMA-3 was sponsored by Kite, a Gilead Company.

Dr. Wierda disclosed research funding from AbbVie and Genentech. 

* Data in the abstract differ from the presentation.

Dear Readers,

As 2018 draws to a close, Clinician Reviews is looking ahead to its 29th year of publication. In 1991, when our publication was founded, it was a unique idea to present information to both NPs and PAs together—a recognition of common educational needs and a unified focus on delivering the best possible patient care. For the past six years, as Editor, I have been privileged to ensure the fulfillment of CR’s editorial purpose—keeping NPs and PAs up to date on all aspects of clinical practice—while navigating changes both internal and external.

When CR started, personal computers existed but were not yet in widespread use (the office had one, to be shared). Manuscripts, peer reviews, even radiographs—all were submitted on paper, via the US Postal Service. How far the world has come in the ensuing decades. Now, we can stay connected to anyone, anywhere, via devices that fit in our pockets.

And so I’m excited to share with you one of the changes we’re making: In 2019, Clinician Reviews will be published 100% digitally! Why? Yes, printing and postage costs have increased to the point of unsustainability (and all that paper is not very environmentally friendly). But most importantly, online publication allows us to provide you with more of what you need for your practice—at any time of day or night, on any device you choose. And this gives us more scope to be creative in presenting information in engaging ways.

To ensure that we are moving in the right direction in making ClinicianReviews.com a more robust and useful resource, we surveyed NPs and PAs like you about our site, our competitors’ sites, and potential new offerings. Your answers were very enlightening, providing us guidance on

Building new functionality to make the site more user friendly

✓ Automatic notification when new content is posted

✓ Video player with a list of recently posted videos

Providing new content, including

✓ Clinical crossword puzzle

✓ Malpractice Chronicle by David Lang (both of which make their debut in this print issue)

Continue to: Offering you must-have content

Offering you must-have content

✓ Enhanced disease-specific content

✓ CE/CME with transcript tracking

✓ Peer-reviewed, evidence-based articles

✓ NP/PA- and MD-specific content

✓ Real-time news and conference reports

To ensure you stay informed about new offerings—and can continue to find the content you’ve enjoyed for years—we invite you to register on our website. You can do so by scanning the QR code below, and as a thank you, you’ll be able to download a free pocket guide, “PURLs in Primary Care.” And don’t forget to bookmark ClinicianReviews.com so that you can easily access our continually updated content.

We’re excited to take this step forward—and as always, we appreciate your support. We’re here to continue to serve the NP and PA professions, so please don’t hesitate to share your feedback and suggestions with us.

Best regards,

Karen J. Clemments

Dear Readers,

As 2018 draws to a close, Clinician Reviews is looking ahead to its 29th year of publication. In 1991, when our publication was founded, it was a unique idea to present information to both NPs and PAs together—a recognition of common educational needs and a unified focus on delivering the best possible patient care. For the past six years, as Editor, I have been privileged to ensure the fulfillment of CR’s editorial purpose—keeping NPs and PAs up to date on all aspects of clinical practice—while navigating changes both internal and external.

When CR started, personal computers existed but were not yet in widespread use (the office had one, to be shared). Manuscripts, peer reviews, even radiographs—all were submitted on paper, via the US Postal Service. How far the world has come in the ensuing decades. Now, we can stay connected to anyone, anywhere, via devices that fit in our pockets.

And so I’m excited to share with you one of the changes we’re making: In 2019, Clinician Reviews will be published 100% digitally! Why? Yes, printing and postage costs have increased to the point of unsustainability (and all that paper is not very environmentally friendly). But most importantly, online publication allows us to provide you with more of what you need for your practice—at any time of day or night, on any device you choose. And this gives us more scope to be creative in presenting information in engaging ways.

To ensure that we are moving in the right direction in making ClinicianReviews.com a more robust and useful resource, we surveyed NPs and PAs like you about our site, our competitors’ sites, and potential new offerings. Your answers were very enlightening, providing us guidance on

Building new functionality to make the site more user friendly

✓ Automatic notification when new content is posted

✓ Video player with a list of recently posted videos

Providing new content, including

✓ Clinical crossword puzzle

✓ Malpractice Chronicle by David Lang (both of which make their debut in this print issue)

Continue to: Offering you must-have content

Offering you must-have content

✓ Enhanced disease-specific content

✓ CE/CME with transcript tracking

✓ Peer-reviewed, evidence-based articles

✓ NP/PA- and MD-specific content

✓ Real-time news and conference reports

To ensure you stay informed about new offerings—and can continue to find the content you’ve enjoyed for years—we invite you to register on our website. You can do so by scanning the QR code below, and as a thank you, you’ll be able to download a free pocket guide, “PURLs in Primary Care.” And don’t forget to bookmark ClinicianReviews.com so that you can easily access our continually updated content.

We’re excited to take this step forward—and as always, we appreciate your support. We’re here to continue to serve the NP and PA professions, so please don’t hesitate to share your feedback and suggestions with us.

Best regards,

Karen J. Clemments

Dear Readers,

As 2018 draws to a close, Clinician Reviews is looking ahead to its 29th year of publication. In 1991, when our publication was founded, it was a unique idea to present information to both NPs and PAs together—a recognition of common educational needs and a unified focus on delivering the best possible patient care. For the past six years, as Editor, I have been privileged to ensure the fulfillment of CR’s editorial purpose—keeping NPs and PAs up to date on all aspects of clinical practice—while navigating changes both internal and external.

When CR started, personal computers existed but were not yet in widespread use (the office had one, to be shared). Manuscripts, peer reviews, even radiographs—all were submitted on paper, via the US Postal Service. How far the world has come in the ensuing decades. Now, we can stay connected to anyone, anywhere, via devices that fit in our pockets.

And so I’m excited to share with you one of the changes we’re making: In 2019, Clinician Reviews will be published 100% digitally! Why? Yes, printing and postage costs have increased to the point of unsustainability (and all that paper is not very environmentally friendly). But most importantly, online publication allows us to provide you with more of what you need for your practice—at any time of day or night, on any device you choose. And this gives us more scope to be creative in presenting information in engaging ways.

To ensure that we are moving in the right direction in making ClinicianReviews.com a more robust and useful resource, we surveyed NPs and PAs like you about our site, our competitors’ sites, and potential new offerings. Your answers were very enlightening, providing us guidance on

Building new functionality to make the site more user friendly

✓ Automatic notification when new content is posted

✓ Video player with a list of recently posted videos

Providing new content, including

✓ Clinical crossword puzzle

✓ Malpractice Chronicle by David Lang (both of which make their debut in this print issue)

Continue to: Offering you must-have content

Offering you must-have content

✓ Enhanced disease-specific content

✓ CE/CME with transcript tracking

✓ Peer-reviewed, evidence-based articles

✓ NP/PA- and MD-specific content

✓ Real-time news and conference reports

To ensure you stay informed about new offerings—and can continue to find the content you’ve enjoyed for years—we invite you to register on our website. You can do so by scanning the QR code below, and as a thank you, you’ll be able to download a free pocket guide, “PURLs in Primary Care.” And don’t forget to bookmark ClinicianReviews.com so that you can easily access our continually updated content.

We’re excited to take this step forward—and as always, we appreciate your support. We’re here to continue to serve the NP and PA professions, so please don’t hesitate to share your feedback and suggestions with us.

Best regards,

Karen J. Clemments

This year’s Vascular Annual Meeting will have a new and elegant air about it, with the introduction of a Gala to benefit the SVS Foundation. It is replacing the traditional President’s Reception, at the request of SVS President Michel S. Makaroun. Tickets are $250 each, of which $150 is a tax-deductible contribution to the SVS Foundation’s general fund, the Greatest Need Fund. The Gala will be held Friday, June 14, at the Gaylord National Resort & Convention Center, the site for VAM. The event will include a silent auction, cocktails, dinner and entertainment. Many details are still in the planning stages and a link to purchase tickets will be available in January. Keep checking the SVS site for future details.

This year’s Vascular Annual Meeting will have a new and elegant air about it, with the introduction of a Gala to benefit the SVS Foundation. It is replacing the traditional President’s Reception, at the request of SVS President Michel S. Makaroun. Tickets are $250 each, of which $150 is a tax-deductible contribution to the SVS Foundation’s general fund, the Greatest Need Fund. The Gala will be held Friday, June 14, at the Gaylord National Resort & Convention Center, the site for VAM. The event will include a silent auction, cocktails, dinner and entertainment. Many details are still in the planning stages and a link to purchase tickets will be available in January. Keep checking the SVS site for future details.

This year’s Vascular Annual Meeting will have a new and elegant air about it, with the introduction of a Gala to benefit the SVS Foundation. It is replacing the traditional President’s Reception, at the request of SVS President Michel S. Makaroun. Tickets are $250 each, of which $150 is a tax-deductible contribution to the SVS Foundation’s general fund, the Greatest Need Fund. The Gala will be held Friday, June 14, at the Gaylord National Resort & Convention Center, the site for VAM. The event will include a silent auction, cocktails, dinner and entertainment. Many details are still in the planning stages and a link to purchase tickets will be available in January. Keep checking the SVS site for future details.

SVSConnect, your online community, is now open! This online space gives members a place for discussion, collaboration and a chance to expand their professional networks. This initial launch starts with a single forum for all members to get signed up and post discussions on everything from case complications and surgical procedures, to research projects, wellness topics and more. Users also have an opportunity to leave general questions for SVS. Login to engage and help shape this community, and your Society, for the future.

SVSConnect, your online community, is now open! This online space gives members a place for discussion, collaboration and a chance to expand their professional networks. This initial launch starts with a single forum for all members to get signed up and post discussions on everything from case complications and surgical procedures, to research projects, wellness topics and more. Users also have an opportunity to leave general questions for SVS. Login to engage and help shape this community, and your Society, for the future.

SVSConnect, your online community, is now open! This online space gives members a place for discussion, collaboration and a chance to expand their professional networks. This initial launch starts with a single forum for all members to get signed up and post discussions on everything from case complications and surgical procedures, to research projects, wellness topics and more. Users also have an opportunity to leave general questions for SVS. Login to engage and help shape this community, and your Society, for the future.

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks. 

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks. 

Photo by Bill Branson

The thrombopoietin receptor agonist romiplostim (NPlate®) is now approved by the U.S. Food and Drug Administration (FDA) to treat pediatric patients 1 year and older who have had immune thrombocytopenia (ITP) for at least 6 months and have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim was originally FDA-approved in 2008 to treat adult patients with chronic ITP who had an insufficient response to the same treatments.

Romiplostim is manufactured by Amgen, Inc.

The FDA based its approval on two double-blind, placebo-controlled clinical trials.

NCT01444417

The phase 3 study (NCT01444417) enrolled 62 pediatric patients 1 year and older who had ITP for at least 6 months. They were refractory to or relapsed after at least one prior therapy.

Investigators randomized them 2:1 to receive romiplostim (n=42) or placebo (n=20).

The starting dose was 1 μg/kg weekly for all ages. The dose was titrated up over a 24-week period to a maximum of 10 μg/kg weekly.

Patients were a median age of 9.5 years (range, 3–17), and 57% were female. A little over half (58%) had baseline platelet counts of 20 x 10⁹/L or less, which was similar in both treatment arms.

Eighty-one percent of romiplostim-treated patients had at least two prior ITP therapies, compared with 70% in the placebo group. One patient in each group had undergone splenectomy.

Twenty-two (52%) of the romiplostim-treated patients had durable platelet responses of 50 x 10⁹/L or greater for at least six weekly assessments during weeks 18 through 25 of treatment. Two (10%) patients in the placebo arm achieved durable platelet responses.

Thirty (71%) romiplostim-treated patients achieved an overall platelet response, defined as a durable or transient platelet response. This compared with four (20%) patients in the placebo group.

Romiplostim-treated patients had platelet counts of at least 50 x 10⁹/L for a median of 12 weeks, compared to 1 week for patients in the placebo arm.

All response endpoints were significant at P<0.05.

NCT00515203

The phase 1/2 study (NCT00515203) enrolled 22 patients who had ITP for at least 6 months prior to study enrollment and were relapsed from or refractory to prior treatment.

Investigators randomized the patients 3:1 to romiplostim (n=17) or placebo (n=5).

Patients were a median age of 10 years (range, 1–17), and 27.3% were female.

Approximately 82% of patients had baseline platelet counts of 20 x 10⁹/L or less, which was similar between the treatment arms.

Eighty-eight percent of patients in the romiplostim arm had at least two prior ITP therapies, as did 100% in the placebo group.

Six patients in the romiplostim group and two in the placebo group had undergone splenectomy.

Of the 17 patients treated with romiplostim, 15 (88.2%) achieved a platelet count of 50 x 10⁹/L or great for 2 consecutive weeks.

The same 15 patients also achieved an increase in platelet count of 20 x 10⁹/L or greater above baseline for 2 consecutive weeks during the treatment period.

None of the placebo-treated patients achieved either endpoint.

The adverse events profile in pediatric patients was compiled from the two trials and reflects a median drug exposure of 168 days for 59 patients.

The most common adverse events, occurring in 25% or more of romiplostim-treated patients, were contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%). These occurred with an incidence at least 5% higher than in the placebo group.

Dosing

The recommended starting dose for pediatric patients is 1 µg/kg based on actual body weight and administered as a weekly subcutaneous injection.

The dose should be adjusted in increments of 1 µg/kg until the patient achieves a platelet count of 50 x 10⁹/L or greater.

The prescribing information recommends reassessing patients’ body weight every 12 weeks.