Romiplostim versus Placebo for Chemotherapy-Induced Thrombocytopenia

Treatment with Romiplostim, a Thrombopoietin-Receptor Agonist, in Thrombocytopenic Patients (Pts) with Low or Intermediate-1 (Int-1) Risk Myelodysplastic Syndrome (MDS): Updated Follow-up Results for Acute Myeloid Leukemia (AML) and Survival from a Randomized, Double-Blind, Placebo (PBO)-Controlled Study

12007 Background: CIT is a common consequence of antineoplastic regimens for gastrointestinal (GI) cancers, occurring in >60% of colorectal cancer patients receiving multiagent chemotherapy. CIT can lead to chemotherapy dose reduction, delay, omission, and discontinuation, potentially worsening outcomes. There are no widely available licensed therapies for this unmet need. Aim: To evaluate the safety and efficacy of the thrombopoietin receptor agonist romiplostim (ROMI) in patients with GI cancers to limit chemotherapy dose modifications from CIT. Methods: This was a phase 3, placebo (PBO)-controlled RCT of patients receiving oxaliplatin-based multiagent regimens for GI cancers with persistent CIT, ie platelets (Plt) ≤85×10 9 /L on day 1 of a scheduled chemotherapy cycle (NCT03362177). Patients from 55 sites in 14 countries were randomized 2:1 to ROMI or PBO for 3 chemotherapy cycles, stratified by baseline Plt (< or ≥50×10 9 /L) and cancer type. Study drug started at 2 μg/kg subcutaneous weekly, adjusted weekly by 1 μg/kg up to 10 μg/kg to target Plt ≥100×10 9 /L in 12 weeks (≤4 weeks at 10 μg/kg). Chemotherapy started when Plt ≥100×10 9 /L (Plt response) or after week 4 per investigator. The primary endpoint was no CIT-induced dose modification of any myelosuppressive agent in either the second or third chemotherapy cycle per independent adjudication committee. Results: Patients (N=165; 109 ROMI, 56 PBO) had colorectal (75%), gastroesophageal (13%), or pancreatic (12%) cancer; 60% were male, 90% White, 4% Black, and 24% Hispanic, with mean (SD) age of 61.4 (11.1) years. Baseline median (range) Plt was 69 (8–85)×10 9 /L; 11% had Plt <50×10 9 /L. Stage IV disease rates were ROMI 65%, PBO 55%. Most (75%) patients completed study drug; 3% discontinued due to adverse events (AEs). The primary endpoint was achieved in 92/109 (84%) patients receiving ROMI vs 20/56 (36%) receiving PBO (odds ratio 10.2; 95% CI 4.6-22.5; P<0.001). Median (range) Plt nadirs were ROMI 87 (14–167)×10 9 /L, PBO 58 (22–95)×10 9 /L; P=0.005. For those with Plt responses (ROMI 97%, PBO 77%), median (95% CI) time to first Plt response was ROMI 1.1 (not estimable) weeks, PBO 2.1 (1.1-3.0) weeks; P<0.001. Treatment-related (TR) AE rates were ROMI: 12%, PBO: 7%, most frequently nausea (2%, 2%) and headache (2%, 0%). TR serious AEs and TRAEs leading to death or discontinuation of study drug or chemotherapy were not observed in either arm. Conclusions: In this first global phase 3 RCT of ROMI vs PBO for CIT, ROMI was well tolerated and efficacious in the treatment and prevention of CIT in GI cancers. These results are potentially practice-changing for a common serious condition encountered routinely in clinical practice worldwide that prevents delivery of on-time, full-dose anticancer therapy. Final results from long-term follow-up will be presented. Clinical trial information: NCT03362177 .

Romiplostim in Thrombocytopenic Patients with Low- or Int-1- Risk MDS Results in Reduced Bleeding without Impacting Leukemic Progression: Final Follow-up Results from a Randomized, Double-Blind, Placebo-Controlled Study

Romiplostim N01 enhances platelet engraftment in ASCT using non-cryopreserved pbscs for plasma cell neoplasms: A single-center phase II study in China

Study protocol, statistical code, and data set are available from Prof Song (email: [email protected]). Supplementary Table S1 Patient, disease, and treatment characteristics of 81 patients with digestive tract cancer and COVID-19 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Comparison of Splenectomy and Treatment Failure Incidence in Nonsplenectomized Patients with Immune Thrombocytopenia (ITP) Receiving Romiplostim or Medical Standard of Care: 1-Year Treatment and 6-Month Safety Follow-up.

Safety and efficacy of romiplostim in children and adolescents with Immune thrombocytopenia: A systematic review

e19542 Background: Non-Hodgkin’s lymphoma, specifically, diffuse large B-cell lymphoma (DLBCL) is most frequently diagnosed among older patients. The utilization of a reduced dose of cyclophosphamide, doxorubicin, vincristine, and prednisone (miniCHOP) chemotherapy-based regimen has an improved tolerance and toxicity profile in select patient populations. Prophylaxis with pegfilgrastim or its biosimilar pegfilgrastim-cbqv is administration on the same day of chemotherapy in all patients with MiniCHOP at The University of Arizona Cancer Center (UACC). We report here on the first study to address the safety and efficacy of same day pegfilgrastim administration in lymphoma patients receiving MiniCHOP. Methods: A retrospective, single center, cohort study was conducted at UACC between October 1, 2013 and October 2020 to evaluate lymphoma patients who were treated with miniR-CHOP and given pegfilgrastim or its biosimilar (pegfilgrastim-cbqv) for FN prophylaxis. The primary objective was to compare the incidence of FN across all cycles of chemotherapy and after the first cycle of chemotherapy in DLBCL patients on miniR-CHOP and provided with next-day versus same-day pegfilgrastim administration. Our secondary outcomes of interests were incidence of chemotherapy-induced neutropenia (CIN) grade 3/4; hospitalization; anti-biotics administration; and chemotherapy dose-reduction or delays. Results: A total of 100 cycles of miniR-CHOP were received, of these pegfilgrastim was administered on same-day of chemotherapy in 95 cycles and five cycles on the next-day of chemotherapy. Among all cycles the incidence of FN was 5.3% vs. 0.0 ( P= 1.00); CIN 3/4 was 10.5% vs. 0.0 ( P= 1.00); hospitalization was 10.5% vs. 20.0% ( P= 0.45), anti-biotics administration was 6.3% vs. 40.0% ( P= 0.05) and the chemotherapy dose delays or reductions was 16.8% vs. 0.0% ( P= 0.99). In the first cycle of chemotherapy, the incidence of FN was 14.3% vs. 0.0% ( P= 1.00), CIN 3/4 was 21.4% vs. 0.0 ( P= 1.00), hospitalization 28.6% vs. 25.0% ( P= 0.99), and the anti-biotics administration was 21.4% vs. 50.0% ( P= 0.53) for same-day vs. next-day study groups. Conclusions: In our analysis, we have shown that same-day pegfilgrastim or pegfilgrastim-cbqv was safe and effective in lymphoma patients receiving miniR-CHOP. There was no significant increase in FN or delayed engraftment in either group. Future prospective studies are warranted to address the safety and efficacy profile of same day pegfilgrastim or a pegfilgrastim biosimilars in elderly lymphoma patients.

12008 Background: There is a lack of approved therapeutic options to ameliorate CIT in patients with solid tumors receiving chemotherapy. Carica papaya leaf extract (CPLE) is known to increase platelet counts (PC) in certain infections. Methods: The PACT study is a triple blinded randomized phase III study conducted in two academic centres in patients with solid tumors receiving chemotherapy and developing at least grade 2 or grade 3 CIT (platelet counts < 75,000 x 10^9/ liter and > 25,000 x 10^9/liter). Patients were randomized 2:1 to CPLE arm (capsule CPLE per oral 1100mg three times daily) or placebo arm ( capsule per oral three times daily), which was continued till PC improved to greater than > 75,000 x 10^9/ liter, requirement for platelet transfusions or D+10 post intervention. Baseline PC were graded as per the Common Terminology Criteria for Adverse Events (CTCAE) grades. The primary endpoint of the study was to evaluate whether CPLE improves PC significantly faster (as assessed on D+4 of intervention) and above 75,000 x 10e9 /L as compared to placebo (spontaneous recovery of platelets). To achieve 80% power to detect a difference between the group proportions of 0.25 (50% to 75%) with an alpha of 0.05, 219 patients were required (146 in CPLE group and 73 in placebo group), assuming 10% loss to follow-up rates. Results: Between March 2020 and October 2024, 219 patients were randomized, of whom 198 patients (CPLE arm: 129; placebo arm: 69) were analysed for outcomes. All the baseline parameters were equally distributed in both the arms (2:1) except the proportion of patients in the placebo and the experimental arms had equal number of patients with grade 3 thrombocytopenia (17/129 vs 17/69; p = 0.049). The most common chemotherapeutic regimens were oxaliplatin based (37%) and carboplatin based (27%). The primary outcome of increasing PC > 75,000 x 10^9/ liter at D+4 was significantly improved by CPLE (83/129, 64% vs 33/69, 48%; p = 0.034) as compared to placebo. This improvement was significantly quicker in subgroups including three weekly regimen vs weekly/biweekly, palliative intent vs. curative, > 2 cycles of chemotherapy (< = 2 cycles vs. > 2 cycles) and body surface area (BSA) < 1.6 vs. more. There were no grade 3 or grade 4 treatment related adverse events associated with CPLE. Conclusions: CPLE is the first therapeutic intervention that appears to improve grade 2 and grade 3 chemotherapy induced thrombocytopenia faster and to a greater extent than placebo in this phase III randomized trial. It should be used as a secondary prophylaxis to maintain the chemotherapy intesnity. There were no major safety concerns with the use of CPLE. Clinical trial information: CTRI/2019/08/020987 .

Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period. We undertook a phase 3, double-blind, placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months' duration who had baseline platelet counts lower than 30,000 per μL. Patients were randomly allocated (in a 2:1 ratio) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months. Randomisation was done centrally with a computer-generated randomisation schedule and was stratified by baseline platelet count (≤ 15,000 per μL), use of treatment for immune thrombocytopenia, and splenectomy status. Patients, investigators, and those assessing data were masked to allocation. Dose modifications were made on the basis of platelet response. Patients were assessed for response to treatment (defined as a platelet count of 50,000-400,000 per μL) weekly during the first 6 weeks and at least once every 4 weeks thereafter; the primary endpoint was the odds of response to eltrombopag versus placebo. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00370331. Between Nov 22, 2006, and July 31, 2007, 197 patients were randomly allocated to treatment groups and were included in the intention-to-treat analysis (135 eltrombopag, 62 placebo). 106 (79%) patients in the eltrombopag group responded to treatment at least once during the study, compared with 17 (28%) patients in the placebo group. The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period (odds ratio 8·2, 99% CI 3·59-18·73; p<0·0001). 37 (59%) patients receiving eltrombopag reduced concomitant treatment versus ten (32%) patients receiving placebo (p=0·016). 24 (18%) patients receiving eltrombopag needed rescue treatment compared with 25 (40%) patients receiving placebo (p=0·001). Three (2%) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo. Nine (7%) eltrombopag-treated patients and two (3%) in the placebo group had mild increases in alanine aminotransferase concentration, and five (4%) eltrombopag-treated patients (vs none allocated to placebo) had increases in total bilirubin. Four (7%) patients taking placebo had serious bleeding events, compared with one (<1%) patient treated with eltrombopag. Eltrombopag is effective for management of chronic immune thrombocytopenia, and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment. These benefits should be balanced with the potential risks associated with eltrombopag treatment. GlaxoSmithKline.

BackgroundLenalidomide treatment in myelodysplastic syndrome (MDS) may lead to thrombocytopenia and dose reductions/delays. This study evaluated the safety and tolerability of the thrombopoietin mimetic romiplostim and its effects on the incidence of clinically significant thrombocytopenic events (CSTEs) in lower risk MDS patients receiving lenalidomide.MethodsPatients were assigned to weekly placebo (n = 12) or romiplostim 500 μg (n = 14) or 750 μg (n = 13) for four 28-day lenalidomide cycles.ResultsThe treatment groups were generally similar with respect to baseline disease characteristics. Del(5q) abnormalities were noted in 1 (8%) patient in the placebo group, 3 (21%) in the romiplostim 500 μg group, and two (15%) in the 750 μg group. CSTEs were noted in 8 (67%) patients in the placebo group, 4 (29%) in the romiplostim 500 μg group, and 8 (62%) in the romiplostim 750 μg group. Throughout the study, median platelet counts trended lower in placebo-treated than in romiplostim-treated patients. Thrombocytopenia-related adjustments in lenalidomide occurred in 6 (50%) patients in the placebo group, 5 (36%) in the romiplostim 500 μg group, and 2 (15%) in the 750 μg group. Although the percentages of patients who received platelet transfusions were similar across treatment groups, there was a trend toward lower numbers of transfusions in both romiplostim groups during each treatment cycle. There were two serious treatment-related adverse events during the treatment period (cerebrovascular accident, placebo; worsening thrombocytopenia, romiplostim 500 μg). Two patients (romiplostim 500 and 750 μg, respectively) had an increase in bone marrow blasts to >20% during treatment, but had no post-treatment biopsy to confirm or exclude the diagnosis of progression to AML.ConclusionsThese data suggest that romiplostim administered to MDS patients during lenalidomide treatment may decrease the frequency of dose reductions/delays due to thrombocytopenia. Additional study is needed to confirm the results of this preliminary trial.Trial registrationClinicalTrials.gov NCT00418665

Efficacy and Safety of Extended Use of Romiplostim Treatment for Chemotherapy-Induced Thrombocytopenia

Irinotecan, mitomycin and cisplatin all demonstrate activity in gastro-oesophageal cancers. This novel combination was administered to outpatients with previously untreated inoperable gastro-oesophageal or pancreatic cancer, in a 28-day cycle. A total of 26 out of 31 patients with gastro-oesophageal cancer and 12 out of 14 patients with pancreatic cancer have been treated with this combination, and were evaluable for response. The overall response rates for patients with gastro-oesophageal cancer was 42%, with a median survival of 9.5 months. In patients with pancreatic cancer, the overall response rate was 42% with a median survival of 8 months. There was a statistically significant increase in survival between those patients who achieved a stable disease response and those who achieved either a partial response or complete response. The toxicity profiles for both cancers were virtually identical. There were five treatment-related deaths, and a high admission rate (42%). Thus irinotecan, mitomycin and cisplatin is a new combination with activity in inoperable upper gastro-oesophageal cancers, but with a high toxicity profile. Future developments include reducing the dose of irinotecan and number of cycles of therapy to four.British Journal of Cancer (2002) 87, 850–853. doi:10.1038/sj.bjc.6600553www.bjcancer.com© 2002 Cancer Research UK

The Effect of Eltrombopag on Platelet Resistance to Apoptosis: The Role of the Bcl-Xl Pathway

Update on immunogenicity in severe asthma: Experience with mepolizumab