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Many patients with cancer receiving chemotherapy will experience chemotherapy-induced thrombocytopenia ( CIT ), which can lead to dose delays or reductions . In an open-label , phase II study presented at the 2017 ASH Annual Meeting , researchers reported that the thrombopoietin receptor agonist romiplostim could correct and prevent recurrence of CIT , compared with observation only .

Romiplostim is U . S . Food and Drug Administration – approved to treat immune thrombocytopenia . The results from this study explored a new indication for romiplostim , lead author Gerald A . Soff , MD , of the Department of Medicine , Hematology Service at Memorial Sloan Kettering Cancer Center in New York , noted during his presentation .

“ We ’ re addressing what I think of as ‘ the holy grail ’ in supportive care ,” he told ASH Clinical News . “ We can fix neutropenia with granulocyte colony stimulating factor , we can fix anemia

Gerald A . Soff , MD with transfusions , but we have no good options for thrombocytopenia . [ With these data ], we have a very clear signal that we ’ re on the right path .”

The study included 40 patients ( mean age = 58 years ; range = 28-77 years ) with solid-tumor cancers , most of whom had gastrointestinal ( GI ) cancer ( n = 22 ). Most people had metastatic disease ( n = 35 ); the remaining patients had locally advanced disease ( n = 5 ).

Only patients who had previously experienced at least four weeks of CIT ( defined as a platelet count < 100,000 / mcL ), despite reductions or delays in chemotherapy , were included in the trial . They were then randomized 2:1 to receive weekly romiplostim or observation only . Patients in the observation cohort whose platelet counts failed to correct to > 100,000 / mcL within three weeks ( primary endpoint ) were permitted to crossover to the romiplostim cohort .

By the time eight patients were enrolled in the observation cohort , an unplanned interim

TABLE 3 . Primary Outcomes in Randomized Patients

Platelet Count Corrected Within 3 Weeks

Interim Analysis ( n = 23 )

Fail to Correct Within 3 Weeks

analysis revealed “ a notable difference in platelet transfusion requirements during that three-week period ,” Dr . Soff said . “ At that point , we dropped the observation arm with approval of the institutional review board and the rest of the patients received romiplostim upfront .”

Of the 32 patients who received upfront romiplostim , the platelet counts of 27 ( 84 %) corrected to > 100,000 / mcL within three weeks ( see TABLE 3 ). Among the five people whose platelet counts failed to return to > 100,000 / mcL , two had protocol violations because chemotherapy was prematurely resumed prior to platelet correction . Twenty-five patients resumed chemotherapy after CIT correction , and weekly romiplostim was titrated to a target platelet count of 150,000 / mcL . The mean effective romiplostim dose for platelet count correction was 2.5 mcg / kg ( range = 1.8-4.1 mcg / kg ). Only one patient had CIT recurrence after resuming chemotherapy .

Romiplostim was well tolerated , Dr . Soff said , with no evidence of bone marrow – related adverse events ( AEs ). Patients receiving romiplostim reported the following AEs : thrombosis ( n = 4 ; 12.5 %), including one symptomatic pulmonary embolism ( PE ), one incidentally identified PE , and two deep vein thromboses . The thrombosis rate was “ well within the expected range for patients with metastatic cancers ,” he added .

Three patients in the romiplostim cohort required platelet transfusions : One patient had an upper GI bleed from a gastric tear , and two received platelet transfusion during terminal hospitalizations for progression of disease .

“ Several patients have been treated for well over a year ,” Dr . Soff noted , and one patient remained on romiplostim for more than three years . The tolerability suggests “ a durable benefit to the patients ,” he added .

The study is limited by its single-center design and the small patient population , Dr . Soff noted , and the results are not generalizable to patients with hematologic malignancies . “ We are planning a randomized , placebo-controlled , phase III study with the primary goal of correcting and maintaining platelet counts with resumption of chemotherapy ,” he said . “ We ’ re also hoping to demonstrate the value of maintaining full-dose chemotherapy on schedule . One would assume there is , but we have to clearly and prospectively demonstrate [ this benefit ].”

Dr . Soff reports receiving financial support from Janssen and Amgen .

Total

p Value

p < 0.001

p < 0.001

REFERENCE

Soff GA , Miao Y , Devlin SM , et al . Romiplostim for chemotherapyinduced thrombocytopenia ( CIT ). Results of a phase 2 trial . Abstract # 289 . Presented at the 2017 American Society of Hematology Annual Meeting , December 10 , 2017 ; Atlanta , GA .

Sarah Marktel , MD

Gene therapy could represent an alternative to hematopoietic stem cell transplantation ( HCT ) – the only curative therapy for beta-thalassemia – and may offer several advantages over HCT , including tailored conditioning with no need for immunosuppression after gene therapy and no risk of graft-versus-host disease or rejection . According to results from a phase I / II trial presented at the 2017 ASH Annual Meeting , patients with transfusion-dependent beta-thalassemia had a significantly reduced need for blood transfusions after receiving a single infusion of cells carrying corrected genes .

Sarah Marktel , MD , of the Hematology and Bone Marrow Transplantation Unit IRCCS San Raffaele Scientific Institute in Milan , Italy , explained during her presentation that the investigational gene therapy protocol used in this trial was based on the high-titer vector GLOBE , a third-generation , self-inactivating lentiviral vector encoding for the human beta globin gene .

“ In the TIGET-BTHAL trial , patients with betathalassemia of any genotype undergo stem cell harvesting , and stem cells are then transferred to the pharmaceutical [ sponsor ] for insertion of the human beta globin gene ,” she said . “ Once genetically corrected , stem cells are infused into the patient after a conditioning regimen … directly in the bone marrow ( BM ).” The hematopoietic stem cells ( HSCs ) are administered into the hip , with the goal of enhancing engraftment and minimizing first-pass intravenous filter .

Three days after gene therapy , previously collected unstimulated autologous peripheral blood ( PB ) leukocytes ( 1-10 × 10 7 CD3 +/ kg ) are reinfused intravenously to promote immune-reconstitution .

The trial began in 2015 , with a goal of treating 10 patients in three age cohorts : three adults ( group 1 ), three patients eight to 17 years ( group 2 ), and four patients three to seven years ( group 3 ). Enrollment was staggered based on evaluation of safety and preliminary efficacy in adult patients before inclusion of pediatric patients .

32 ASH Clinical News January 2018 Annual Meeting Edition