Assessing the effect of immunosuppressive agents for immune-related adverse event management on tumor response.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3066-3066
Author(s):  
Pankti Reid ◽  
Daniel Olson ◽  
Thomas Gajewski
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Tumor Response ◽  
Immunosuppressive Agents ◽  
Objective Response ◽  
Treatment Algorithm ◽  
Tumor Control ◽  
High Dose ◽  
High Grade ◽  
Steroid Dependent

3066 Background: High grade immune-related adverse events (irAEs) to cancer immune checkpoint inhibitors (ICI) require considerable immunosuppression (IS) with high-dose steroids and steroid-sparing IS (SSIS) for steroid-dependent cases. T lymphocyte-specific IS has generally been avoided or used with significant caution due to the fear that these agents may negatively impact ICI efficacy. We sought to determine whether T cell-specific IS agents, such as calcineurin inhibitors (CNIs), have an adverse effect on tumor control when compared to other immunomodulatory drugs (IMDs). Methods: We retrospectively analyzed clinical annotations of adult patients treated with ICIs for malignancy from 1/1/2000-12/31/2019, highlighting patients who were managed with SSIS, specifically those most commonly used for autoimmune disease therapy. Topical IS use was excluded. Patients were categorized as tumor responders or non-responders, and irAEs were graded according to National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Progression-free survival (PFS) was assessed via Kaplan-Meier curve. Results: 1331 unique individuals were prescribed ≥1 ICIs, with 526 prescribed systemic steroids (39.5%) and 90 (6.8%) patients prescribed SSIS agents, 25 patients with >1 SSIS: mycophenolate (39), methotrexate (26), leflunomide (5), azathioprine (3), rituximab (24), tocilizumab (3), infliximab (8), etanercept (1), adalimumab (1), golimumab (1) and CNIs (18): cyclosporine, tacrolimus. IMDs hydroxychloroquine (6) and sulfasalazine (5) were also prescribed. The objective response rate was 50.0% in the CNI group compared to 45.5% in the IMD cohort and 45.4% in the irAE group (CTCAE grade matched) with steroids alone without any SSIS. Median PFS were compared between CNI cohort (5.4 months, range 1.3-34 months) to IMD (1.1 months, range 0.4-6.4, p=0.02) and steroid alone (2.4 months, range 0.69-17.7, p=0.48). Multiple regression analysis identified irAE presence as an independent correlates to tumor response (p=0.02). Conclusions: T cell-specific IS should not be excluded from irAE treatment algorithm as we observed that PFS was comparable to immunomodulators and similar efficacy was observed compared to steroids alone. Rapid identification and management of irAEs can help mitigate morbidity but there are virtually no reliable clinical trials to guide irAE management with SSIS. These findings support the need for larger, prospective evaluation of immunosuppression use for high grade irAE therapy.

scholarly journals An Observational Study of the First Experience with Bevacizumab for the Treatment of Patients with Recurrent High-Grade Glioma in Two Belgian University Hospitals

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Huylebrouck ◽  
S. Lv ◽  
J. Duerinck ◽  
A. Van Binst ◽  
I. Salmon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Response ◽  
Metabolic Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
University Hospitals ◽  
Phase Ii Trials ◽  
Antiangiogenic Effect

Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas (HGG) in phase II clinical trials.Patients and Methods. Data were collected from patients with recurrent HGG who initiated treatment with BEV outside a clinical trial protocol at two Belgian university hospitals.Results. 19 patients (11 M/8 F) were administered a total of 138 cycles of BEV (median 4, range 1–31). Tumor response assessment by MRI was available for 15 patients; 2 complete responses and 3 partial responses for an objective response rate of 26% for the intent to treat population were observed on gadolinium-enhanced T1-weighted images; significant regressions on T2/FLAIR were documented in 10 out of 15 patients (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients. The six-month progression-free survival was 21% (95% CI 2.7–39.5). Two patients had an ongoing tumor response and remained free from progression after 12 months of BEV treatment.Conclusions. The activity and tolerability of BEV were comparable to results from previous prospective phase II trials. Reduced uptake on PET suggests a metabolic response in addition to an antiangiogenic effect in some cases with favorable clinical outcome.

scholarly journals Checkpoint inhibitors plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

2019 ◽  
Vol 5 (9) ◽  
pp. FSO421 ◽  
Author(s):  
Aung Myint Tun ◽  
Kyaw Zin Thein ◽  
Wai Lin Thein ◽  
Elizabeth Guevara
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell ◽  
High Grade ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Treatment

Background: We conducted a meta-analysis to evaluate the efficacy and safety of upfront add-on immunotherapy for advanced non-small cell lung cancers (NSCLC). Methods: We performed a literature search on first-line chemotherapy ± immunotherapy in NSCLC. We utilized Revman version 5.3 to calculate the estimated pooled hazard ratio for overall survival (OS) and progression-free survival (PFS) and pooled risk ratio for objective response rate (ORR), all-grade and high-grade adverse events with 95% CI. Results: We analyzed 4322 patients. The pooled hazard ratios for OS, PFS and ORR were 0.74 (95% CI: 0.62–0.88; p = 0.0007), 0.62 (95% CI: 0.57–0.68; p = 0.00001) and 1.51 (95% CI: 1.3–1.74; p = 0.00001), respectively. The pooled risk ratios for all-grade and high-grade adverse events were 1.01 (95% CI: 0.99–1.03; p = 0.27) and 1.17 (95% CI: 1.07–1.28; p = 0.0006), respectively. Conclusion: Add-on immunotherapy significantly improves PFS, OS and ORR for the first-line treatment of advanced NSCLC with a reasonable safety profile.

Procarbazine and High-Dose Tamoxifen as a Second-Line Regimen in Recurrent High-Grade Gliomas: A Phase II Study

1999 ◽  
Vol 17 (2) ◽  
pp. 645-645 ◽  
Author(s):  
Alba A. Brandes ◽  
Mario Ermani ◽  
Sergio Turazzi ◽  
Elvira Scelzi ◽  
Franco Berti ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Chemotherapy Regimen ◽  
Phase Ii Study ◽  
Tumor Control ◽  
High Dose ◽  
High Grade ◽  
Second Line ◽  
First Line ◽  
High Grade Gliomas

PURPOSE: A phase II study was conducted in patients with high-grade gliomas that recurred after surgery plus radiotherapy and a first-line nitrosourea-based regimen. Our aim was to investigate the efficacy of procarbazine (PCB) combined with high-dose tamoxifen in relation to tumor control, toxicity, and time to progression (TTP). PATIENTS AND METHODS: Fifty-three patients were treated with procarbazine in repeated 30-day courses at 100 mg/m2/d plus tamoxifen 100 mg/d, with a 30-day interval between courses. Thirty-four patients had been pretreated with a first-line nitrosourea-based chemotherapy regimen (group A), and 19 patients had also been pretreated with a second-line chemotherapy regimen consisting of carboplatin and teniposide (group B). Twenty-one of the patients had also been procarbazine pretreated, whereas the remaining 32 patients were not procarbazine pretreated. RESULTS: The response was assessed in 51 patients, 28 of whom had glioblastoma multiforme (GBM) and 23 of whom had anaplastic astrocytoma (AA). There were two complete responses (CR) (4%) and 13 partial responses (PR) (25.5%). The overall response rate (CR + PR) was 29.5% (SE, 6.4; 95% confidence interval [CI], 23 to 35.8). Seventeen patients (32%) had stable disease (SE, 6.2; 95% CI, 21 to 33.6). The median TTP was 13 weeks for patients with GBM and 33 weeks for patients with AA (P = .006). The median survival time (MST) was 27 weeks for patients with GBM and 57 weeks for those with AA (P = .006). CONCLUSION: Combined PCB and tamoxifen as a second-line regimen gave a reasonably high response rate in patients with heavily pretreated high-grade gliomas. However, although it resulted in an improvement in the patients' quality of life and/or performance status, it was not followed by an increased TTP or MST.

Intrathecal Liposomal Cytarabine (Depocyt) Is Safe and Effective for Prevention of Meningeal Disease in Patients with Acute Lymphoblastic Leukemia and High-Grade Lymphoma Treated with the HyperCVAD Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4594-4594 ◽  
Author(s):  
Brian McClune ◽  
Francis Buadi ◽  
Naveed Aslam ◽  
Donna Przepiorka
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adverse Events ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Liposomal Cytarabine ◽  
High Grade ◽  
Platelet Recovery ◽  
Significant Difference ◽  
Meningeal Disease

Patients with acute lymphoblastic leukemia (ALL) and high-grade lymphoma have a 10–20% risk of meningeal disease during induction and in remission when given standard-dose chemotherapy. This risk has been reduced to about 1% using intrathecal prophylaxis with cytarabine and methotrexate in addition to the systemic regimen of hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyperCVAD) alternating with high-dose methotrexate-cytarabine (MA). The discomfort and potential adverse events with frequent lumbar punctures may impair patient compliance. Liposomal cytarabine (Depocyt) is an intrathecal preparation of cytarabine with a prolonged half-life. Use of Depocyt could potentially reduce the number of lumbar punctures needed for routine neuroprophylaxis. We reviewed the tolerability and activity of Depocyt for neuroprophylaxis in 15 patients treated with the hyperCVAD regimen. The cohort included 12 males and 3 females of median age 48 years (range, 23–72 years) with precursor B-cell ALL (8), T-cell ALL (3), Burkitt lymphoma and HIV (2), Ph-positive ALL (1), and lymphoblastic lymphoma (1). The patients received a total of 65 cycles of systemic chemotherapy, 36 with hyperCVAD and 29 with MA. Depocyt was given IT or IO in 33 cycles, methotrexate IT in 5, and no intrathecal therapy in 27. When treated with Depocyt, patients also received dexamethasone pre- and postmedication.. The planned dose of Depocyt was 50 mg for all patients, but after one serious adverse event, the dose was reduced to 25 mg when administered by Omaya. Depocyt was instilled on a median of day 8 of the cycle (range, −4 to 13). To date, a meningeal relapse has not occurred in any of the patients. Although minor neurological events (transient headache or neckache) were not uncommon, there were two serious adverse events. One patient developed a severe but transient headache during the fourth cycle and was readmitted for pain control. A second patient received Depocyt four days prior to MA. Shortly after completing chemotherapy, this patient developed hyponatremia and somnolence. The neurological status normalized after several days with supportive care alone. Since leakage of Depocyt into the peripheral blood might cause myelosuppression, hematologic recovery was also assessed. There was a significant difference in time to ANC>500 (p=0.02) and platelets >20,000 (p=0.005) between hyperCVAD and MA cycles, so hematologic recovery was assessed separately for these regimens, as shown in the Table. Median Day of Hematopoietic Recovery Cycle Outcome All Cycles Depocyt No IT PX MTX IT “1” indicates the platelet count did not fall below 20,000 during that cycle. HyperCVAD ANC>500 15 15 14 16.5 Plts>20,000 1 1 1 1 MA ANC>500 16 16 16 15 Plts>20,000 13 13 14 15 There were no significant differences in time to neutrophil or platelet recovery between neuroprophylaxis regimens. Three patients received cranial or craniospinal radiation to compete neuroprophylaxis prior to allogeneic stem cell transplantation without notable neurotoxicity after transplantation. We conclude that it is safe to use a single dose of Depocyt (50 mg IT or 25 mg IO) following completion of administration of chemotherapy (around Days 6 – 8) during each cycle of the hyperCVAD regimen. This approach should be studied in a randomized trial to further assess its efficacy in comparison to more frequent instillations of methotrexate/cytarabine.

Adoptive T-cell therapy combined with intra-lesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20022-e20022
Author(s):  
Amir Khammari ◽  
Jean-Marc Limacher ◽  
Jean-Michel NGuyen ◽  
Melanie Saint-Jean ◽  
Gaelle Quereux ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Translational Research ◽  
Stable Disease ◽  
Objective Response ◽  
Interferon Γ ◽  
Adoptive T Cell Therapy ◽  
Surgical Biopsy ◽  
T Cell Therapy

e20022 Background: The purpose of this study was to evaluate the feasibility, safety and efficacy of adding intra-tumoral injections of TG1042 (Adenovirus 5 expressing Interferon-γ) to adoptive T cell therapy in patients with advanced stage melanoma. Methods: This was a monocentric phase I/II study. The main inclusion criteria were: stage IIIc/IV melanoma, age 18 to 75, at least one injectable metastasis. Tumor infiltrating lymphocytes (TILs) produced from a surgical biopsy of a lesion were infused on days 1 and 29 followed by IL2 injections (6M UI daily) for 10 days. TG1042 was injected at the dose of 5x1010 viral particles per lesion (in up to 6 lesions) every 2 weeks from day -15 to month 2 and then every month up to month 11 or progression. Primary objective was the safety of the procedure; secondary objectives included response according to RECIST and translational research. Results: Eighteen patients have been included. The TILs production was successful in 16 of them. Minor erythema at the TG1042 injection site as well as minor to moderate flu-like symptoms linked to IL2 injections were the most frequent adverse events observed. No grade 3 or 4 treatment related adverse events was recorded. Among the 13 patients evaluable for tumor response 4 patients (31%) had an overall objective response (2 complete, 2 partial), 1patient had a stable disease and 8 progressed. When considering only the injected lesions 6 (46%) had an objective response (3 complete, 3 partial), 3 had a stable disease and 4 progressed. Distant responses in non-injected lesions were observed for 2 patients. Translational research on cutaneous biopsies before and after injections (3 months) showed an increase of CD8 T lymphocytes, IFN-γ and STAT 1 expression in 3 patients. Conclusions: This study demonstrates that co-delivery of TILs and intra lesional TG1042 is feasible and safe. Stimulation of innate immunity by adenovirus expressing interferon-γ could contribute to reverse the immunotolerant profile of the tumour environment. These results support to further explore combined immunotherapies in the treatment of melanoma. Clinical trial information: NCT01082887.

Multidisciplinary team management for high grade immune-related adverse events (irAEs): A single center experience.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15076-e15076
Author(s):  
PRABHSIMRANJOT SINGH ◽  
Osama Abu-Shawer ◽  
Amanda Brito ◽  
Eric Yenulevich ◽  
Shilpa Grover ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Massachusetts General Hospital ◽  
Average Length ◽  
Immunosuppressive Agents ◽  
Future Research ◽  
Inpatient Service ◽  
High Grade

e15076 Background: Immune checkpoint inhibitors (ICIs) are increasingly used in the management of cancer. High grade irAEs are uncommon but can be severe and require hospital admission. There is an urgent need for early identification and triage of patients with irAEs in order to improve their management and outcomes. Methods: We established Immunotherapy toxicity (ITOX) team as the first in nation inpatient service at DFCI and Brigham and Women's Hospital (BWH) along with our partners at Massachusetts General Hospital (MGH) that is specifically devoted to mitigating irAEs. The ITOX service is consistent of 2 PAs and a medical oncology attending with an expertise in immunotherapy. The service utilizes algorithms that are modified from the ASCO and NCCN guidelines by our medical subspecialty experts at BWH. The service uses a multi-disciplinary approach with around the hour consulting service from experts in the field including GI, pulmonary, endocrinology and others. We leveraged EPIC to triage patients who are admitted to BWH and have ever received or currently on immune checkpoint inhibitors (ICIs). The daily list generated by EPIC is then curated manually by a PA to identify patients with potential irAEs. Results: A total of 138 patients with high grade irAEs were admitted to BWH between June 2018 and June 2019. Seventy percent of the 201 irAEs- related admissions were to ITOX service (70% accuracy in triaging). Most common irAEs was colitis (31%), pneumonitis (28%) and hepatitis (13%) which is consistent with the most common reported irAEs due to ICIs. Eighty five percent of the patients had grade 3 irAEs and 15% were admitted with life threatening grade 4 adverse events. About half of the patient had received ICI monotherapy; 33% received combination of ICI and non-ICI (chemotherapy or targeted therapy) and 17% received combination of ICIs. Most patients responded to steroids and only 9% had steroid-refractory irAEs requiring other immunosuppressive agents. The average length of stay for irAEs-related admission was 11 days with readmission rate of 26% within a year. Over 50 patients consented for tissue and blood biospecimen collection at the time of toxicity. Conclusions: We demonstrated the feasibility of empowering EMR to accurately triage patients with suspected irAEs to the ITOX service that is supported by institution developed guidelines and specialists. Our model is adaptable in major academic centers and can have major impact on quality improvement and future research studies that can be conducted in this unique setting.

scholarly journals Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM

2019 ◽  
Vol 15 (3) ◽  
pp. 56-69 ◽  
Author(s):  
M. I. Volkova ◽  
A. M. Abdelgafur ◽  
M. T. Aivazov ◽  
Z. V. Amoev ◽  
K. G. Babina ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Adverse Events ◽  
Observational Study ◽  
Response Rate ◽  
Objective Response ◽  
Tumor Control ◽  
Efficacy And Safety ◽  
Multicenter Observational Study ◽  
Grade Iii

Objective: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy.Material. Russian multicenter observational study ROSLERCM included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23–73) years, a male-to-female ratio – 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8 %)). More than 2 lines of previous therapy were administered in 45 (61.6 %) cases. Most patients were diagnosed with multiple metastases (71 (97.3 %)) in >1 site (61 (83.6 %)). Nephrectomy was performed in 87.7 % (64/73) of cases. At the combined therapy start ECOG PS 2–4 was registered in 16 (20.5 %), poor prognosis according to IMDC score – in 33 (45.2 %) patients. Median follow-up was 9.7 (1–26) months.Results. Median progression-free survival achieved 16.9 (95 % confidence intervals (CI) 12.1–20.6), overall survival – 20.8 (95 % CI 15.7–25.9) months. Objective response rate was 11 % (8/73); tumor control was reached in 93.2 % (68/73) of cases. Median objective response duration was 10.5 (4.3–16.8) months, tumor control duration – 10.0 (2.5–17.5) months. Any adverse events developed in 83.6 % (61/73), adverse events grade III–V – in 23.3 % (17/73) of cases. Most frequent AE grade III–IV were diarrhea (10 (13.6 %)) and arterial hypertension (6 (8.2 %)). Unacceptable toxicity demanded treatment cancellation in 4.2 % (3/73), therapy interruption – in 30.1 % (22/73) and dose reduction – in 32.9 % (24/73) of patients.Conclusion. Unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with similar survival, lower objective response rate, and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.

scholarly journals Association of Survival and Immune-Related Adverse Events With Anti-PD-1/PD-L1 and Anti-CTLA-4 Inhibitors, Alone or Their Combination for the Treatment of Cancer: A Systematic Review and Meta-Analysis of 13 Clinical Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Leyin Zhang ◽  
Leitao Sun ◽  
Yiwen Zhou ◽  
Jieru Yu ◽  
Yingying Lin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Combination Therapy ◽  
Adverse Events ◽  
Survival Benefit ◽  
Data Extraction ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade ◽  
Bias Analysis

BackgroundCancer, with sustained high mortality, is a worldwide threat to public health. Despite the survival benefit over conventional therapies shown in immune checkpoint inhibitor (ICI), only a minority of patients benefit from single ICI. But combination therapy holds the promise of achieving better efficacy over monotherapy. We performed a systematic review and meta-analysis to assess the efficacy and safety of ICI-based combination therapy for cancer.MethodsA search was conducted to retrieve relevant studies in electronic databases and major conferences. Two investigators independently performed data extraction, making a systematic data extraction, assembly, analysis and interpretation to compare the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), all and high grade immune related adverse events (IRAEs) between combination therapy and monotherapy. Therefore, only the studies satisfying the criteria were included. Finally, we performed subgroup, sensitivity, and publication bias analysis to examine the heterogeneity and bias of resources.ResultsA total of 2,532 patients from thirteen studies were enrolled. Compared to ICI alone, combination therapy, with a high risk and high grade IRAEs for the majority of all, offers a better survival benefit (OS: HR: 0.86, 95% CI: 0.76 to 0.98; PFS: HR: 0.79, 95% CI: 0.69 to 0.90) and objective response (ORR: RR: 1.91, 95% CI: 1.40 to 2.60).ConclusionsICI-based combination therapy was confirmed as the optimum treatment for cancer, especially when using specific dosage and regimen to treat certain tumor types with no absolute demand for the detection of PD-L1 expression. Meanwhile, attention should also be paid on potential toxicity, especially the IRAEs.

Low dose IL-2 in patients with steroid-dependent dysimmune manifestations associated with myelodysplastic syndromes: a three-case report

Rheumatology ◽  
2020 ◽  
Author(s):  
Marion Corfmat ◽  
Christophe Willekens ◽  
Julien Vinit ◽  
Guillaume Bussone ◽  
Pierre Fenaux ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myelodysplastic Syndromes ◽  
Low Dose ◽  
Response Rate ◽  
Immunosuppressive Agents ◽  
Relapsing Polychondritis ◽  
Joint Involvement ◽  
Immune Disorders ◽  
Serious Adverse Events ◽  
Steroid Dependent

Abstract Objectives Systemic inflammatory and autoimmune diseases can be associated with myelodysplastic syndromes. Current treatments (steroids, immunosuppressive agents, biologics) are unsatisfactory because of their low response rate, dependence or adverse events. We aimed at evaluating the effects of low doses of IL-2 (ld-IL2) as a regulatory T-cell inducer in this context. Methods We treated three patients with ld-IL2 with myelodysplastic syndromes and an associated dysimmune disorder (polymyalgia rheumatic, relapsing polychondritis associated with Sweet’s syndrome and vasculitis with cutaneous and joint involvement, respectively). All three patients were dependent on steroids and refractory to biologics or azacitidine. They received doses of 1–1.5 million units of proleukin/day during 5 days and then every fortnight. Results The treatment led to a clinical improvement and steroid sparing in 2/3 patients with no serious adverse events, and no progression of the disease. Conclusion Our results support the investigation of ld-IL2 in MDS associated with immune disorders in controlled clinical studies.

scholarly journals Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002)

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuankai Shi ◽  
Jianqiu Wu ◽  
Zhen Wang ◽  
Liling Zhang ◽  
Zhao Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Lymphoma ◽  
Objective Response ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Peripheral T Cell Lymphoma ◽  
Serious Adverse Events ◽  
Phase 2 Study

Abstract Background Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. Results Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. Conclusions In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. Trial registration: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

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