scholarly journals Anlotinib Alone or in Combination With Temozolomide in the Treatment of Recurrent High-Grade Glioma: A Retrospective Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qunying Yang ◽  
Chengcheng Guo ◽  
Xiaoping Lin ◽  
Lili Luo ◽  
Zhenqiang He ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Rank Test ◽  
Cancer Center ◽  
High Grade ◽  
Karnofsky Score ◽  
Free Survival ◽  
Grade 3

Background: Anlotinib is a multi-target anti-angiogenic agent. This retrospective study aimed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide for the treatment of recurrent high-grade glioma.Materials and Methods: The clinical data of patients with recurrent high-grade glioma treated with anlotinib alone or in combination with temozolomide in our cancer center were collected and analyzed. Treatment response was evaluated according to the response assessment for neuro-oncology criteria. Progression-free survival, progression-free survival at 6 months, overall survival, and overall survival at 12 months were evaluated by Kaplan–Meier method and compared by log-rank test.Results: Between August 2019 and December 2020, 31 patients with recurrent high-grade glioma (21 of grade 4 and 10 of grade 3) were enrolled in this study. Seventeen patients received anlotinib alone and 14 received anlotinib plus temozolomide. All patients were heavily treated, the median lines of previous treatments were 2, and the median Karnofsky score was 60. At the data cutoff date, the median progression-free survival was 4.5 months and the progression-free survival at 6 months was 43.5%. The median overall survival was 7.7 months, and the overall survival at 12 months was 26.7%. The progression-free survival at 6 months and the overall survival at 12 months for 21 patients with grade 4 glioma was 40.2 and 27.9%, respectively. The tumor objective response rate was 41.9% in all patients and 33.3% in patients with grade 4 glioma. No grade 3 or worse treatment-related adverse events were recorded during the treatment.Conclusion: Anlotinib alone or in combination with temozolomide showed encouraging efficacy and favorable tolerability in patients with recurrent high-grade glioma who had been heavily treated.

scholarly journals Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

2021 ◽  
Author(s):  
Yang Wang ◽  
Jun Nie ◽  
Ling Dai ◽  
Weiheng Hu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Significant Difference ◽  
Grade 3 ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p  = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience

2020 ◽  
pp. 107815522092068
Author(s):  
Ozkan Alan ◽  
Tugba Akin Telli ◽  
Tugba Basoglu Tuylu ◽  
Rukiye Arikan ◽  
Nazım Can Demircan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Idh1 Mutation ◽  
High Grade ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Ecog Ps

Purpose Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. Methods Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. Results At the time of diagnosis, the median age was 48 (17–77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1–68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). Conclusion Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.

scholarly journals Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial

2019 ◽  
Vol 37 (11) ◽  
pp. 867-875 ◽  
Author(s):  
Celeste Lebbé ◽  
Nicolas Meyer ◽  
Laurent Mortier ◽  
Ivan Marquez-Rodas ◽  
Caroline Robert ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
End Point ◽  
Phase Iiib ◽  
Grade 3

PURPOSE Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination. PATIENTS AND METHODS Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points. RESULTS At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group. CONCLUSION The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.

scholarly journals Real-world outcomes in patients with metastatic renal cell carcinoma according to risk factors: the STAR-TOR registry

2021 ◽  
Author(s):  
Arne Strauss ◽  
Marianne Schmid ◽  
Michael Rink ◽  
Michael Moran ◽  
Stephan Bernhardt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Cancer Center ◽  
Clinical Trial Registration ◽  
Free Survival

Aim: Examine outcomes in sunitinib-treated patients by International Metastatic RCC Database Consortium (IMDC) or Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors. Patients & methods: Patients enrolled in STAR-TOR registry (n = 327). End points included overall survival, progression-free survival and objective response rate. Results: Overall survival was similar for IMDC 0 versus 1 (p = 0.238) or 2 versus ≥3 (p = 0.156), but different for MSKCC (0 vs 1, p = 0.037; 2 vs ≥3, p = 0.001). Progression-free survival was similar for IMDC 2 versus 3 (p = 0.306), but different for MSKCC (p = 0.009). Objective response rate was different for IMDC 1 (41.9%) and 2 (29.5%) and similar for MSKCC 1 (34.4%) and 2 (31.0%). Conclusion: Outcome data varied according to IMDC or MSKCC. MSKCC model accurately stratify patients into risk groups. Clinical trial registration: NCT00700258 (ClinicalTrials.gov)

scholarly journals Bevacizumab Use for Recurrent High-Grade Glioma at McGill University Hospital

2013 ◽  
Vol 40 (2) ◽  
pp. 241-246 ◽  
Author(s):  
Solmaz Sahebjam ◽  
Evgenia Garoufalis ◽  
Marie-Christine Guiot ◽  
Thierry Muanza ◽  
Rolando Del Maestro ◽  
...  
Keyword(s):  
Safety Profile ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
University Hospital ◽  
High Grade ◽  
Mcgill University ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Endothelial Growth Factor

Background:Bevacizumab, a humanized recombinant anti-vascular endothelial growth factor antibody, was approved in Canada in 2010 for the treatment of high-grade glioma. We report the effectiveness and safety of bevacizumab in the treatment of patients with recurrent high-grade gliomas at a single institution.Methods:Twenty-seven consecutive patients with high-grade glioma (anaplastic glioma and glioblastoma) at first or subsequent relapse were treated with bevacizumab alone or in combination with chemotherapy. The primary endpoint was progression-free survival (PFS) and secondary endpoints were objective response rate, six month PFS, overall survival (OS), and safety profile.Results:The clinical benefit rate (complete and partial responses plus stable disease) was 59%. Median PFS was 4.3 (95% CI, 3.0-10.9) months, with a six month PFS rate of 43%. Median OS after current relapse was 8.9 (95% CI, 5.8-not reached) months. Ten episodes of grade 3/4 adverse events were observed in nine patients, including fatigue (n = 3), thrombocytopenia (n = 4), and myelotoxicity, febrile neutropenia, and pulmonary embolism (each n = 1).Conclusions:We consider the efficacy and safety profile of bevacizumab is comparable to other cohorts of patients treated for recurrent high-grade glioma at other international institutions.

Correlation between PD-L1 level and immunotherapy outcome in NSCLC in Lebanon, 2012-2018: A multicenter observational review.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20524-e20524
Author(s):  
Ahmad Ghoche ◽  
Lewis Nasr ◽  
Saada Diab ◽  
Fadi Nasr
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Free Survival ◽  
Lung Cancer Patients ◽  
Checkpoint Pathway ◽  
Grade 3 ◽  
Line Of Therapy

e20524 Background: Immunotherapy targeting the PD1/PDL1 checkpoint pathway represents an important innovation in lung cancer treatment. In our research, we evaluate the correlation of PD-L1 expression with clinical outcomes (progression free survival, overall survival, objective response rate) in lung cancer patients in 4 centers in Lebanon. Methods: The 57 patients enrolled in this observational study were stage IIIB/IV NSCLC and SCLC who received immunotherapy with nivolumab, pembrolizumab or atezolizumab at any line of treatment, and were recruited between February 2012 and august 2018. Immunotherapy was continued until progression, death or unacceptable toxicity. PD-L1 expression was assessed on tumor samples either on diagnosis or at progression. Patients were divided into 3 categories according to PD-L1 level (< 1, 1-49, > 50%). Progression free survival defines the time from randomization to disease progression after each line of therapy. Overall survival defines time from randomization to death from any cause. Results: 70.18% had adenocarcinoma, 26.32% had squamous cell carcinoma, 1.75% had small cell lung cancer and one pathology was missing from the file. 66.66% were stage IV at diagnosis, 26.31% were stage 3. PD-L1 expression was > 50% in 40.35% of patients, 24.56% had a level between 1 and 50% and the remaining had a value of less than 1%. PD-L1 was missing or not done in 15.79%. Median PFS was 13.9 months. Median OS was 14.2 months. 22.81% received immunotherapy as first line and 75% of the remaining patients upon first progression. PFS1 was 4.2 months. Mean time to first progression on immunotherapy was 3.6 months in patients with PD-L1 > 50%, 10.5 months in PD-L1 between 1 and 50% and 14.3 months in those who had PD-L1 < 1%. At the date of data cutoff, 49.12 % of patients were still receiving immunotherapy. No grade 3 or 4 immune related adverse events were seen during follow-up. Conclusions: The efficacy and safety of anti-PD-1 medications for advanced NSCLC were comparable in real-world and clinical settings. Prediction of treatment response from tumor PD-L1 expression seemed less practical than that was expected

High-grade glioma of central nervous system: Single center treatment experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14040-e14040
Author(s):  
Nur Olgun ◽  
Deniz Kızmazoğlu ◽  
Batuhan Özdoğar ◽  
Emre Çeçen ◽  
Ceren Kızmazoğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
Event Free Survival ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
One Year ◽  
Overall Survival Rates

e14040 Background: To evaluate characteristics and treatment responses of patients with high grade gliomas (HGG) in our center Methods: Medical files of patients with malignant CNS tumors between 1987-2020 were analyzed retrospectively. There were 44 patients with HGG. Results: Diagnosis of patients as follows: 21 pons glioma, 2 anaplastic astrocytoma, 11 anaplastic ependimoma, 7 glioblastoma multiforme, 1 glioblastoma, 2 gliomatosis cerebri. The median age at diagnosis was 6,5 yrs (7 – 17 yrs), M/F:25/19. Age distrubution: <5 yrs 12 patients, 5-10 yrs 18 patients, 10-18 yrs 14 patients. The most frequent complaints for pons gliomas: cranial nerve paralysis (52%), visial impairment (48%), headache (38%), power loss (43%) and speech disorder (30%). Surgery was performed to extrinsic component of mass in 3 patients of pons gliomas. For other HGG: 7 subtotal resection and 16 gross total resection had performed. Seven patients died before RT. And other 37 patients received radiotherapy. RT total doses varied between 50-60 Gy. Seven patients were not received chemotherapy, 3 of them died before chemo, and others received only RT. Chemotherapy protocoles were changed over the years: For pons gliomas, MOPP (Mechlorethamine, vincristine, prednisone, procarbazine) in 3 patients, NOPP (nitrosourea, vincristine, prednisone, procarbazine) in 2 patients, only ICE (Ifosfamide, carboplatin, cisplatin) in five patients, oral cyclophosphamide in one patient, temozolamide in one patient and temo + bevacizumab in one patient. Last 3 patients received nimotuzumab-vinorelbine after ICE and temo. For other HGGs, platin based regimens used fort he first line treatment. Temozolamide-bevacizumab, irinotecan-temsirolimus combinations were the other options as second and also third line treatments. Median progression free survival time was 6 mos (2 weeks -25 mos) for pons gliomas, for other gliomas median progression free survival time was 14 mos (0 -74 mos). For pons gliomas: Event free survival rate for 6 mos was 75%, for one year was 17%, One year, 18 mos, and two years overall survival rates were 84%, 52% and 10% respectively. For other HGGs: Event free survival rate for one year and two years were 57% and 17% respectively. One year and two years overall survival rates were 73% and 36% respectively. Conclusions: High grade glioma is a group of tumor in which still the helplessness experienced in treatment. Despite radiotherapy and chemotherapy, prognosis is very poor. The progression free and overall survival rates of patients were similar to literature. With new developments in molecular pathology, as the use of molecular target therapies, the progression free survival rates newly will improve.

Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

2018 ◽  
Vol 36 (8) ◽  
pp. 728-734 ◽  
Author(s):  
David S. Siegel ◽  
Meletios A. Dimopoulos ◽  
Heinz Ludwig ◽  
Thierry Facon ◽  
Hartmut Goldschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Rank Test ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Risk Of Death ◽  
End Point ◽  
Grade 3

Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity. After 18 cycles, all patients received Rd only. Progression-free survival was the primary end point; OS was a key secondary end point. OS was compared between treatment arms using a stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8 months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it was 6.5 months longer for KRd versus Rd among patients receiving ≥ two prior lines of therapy. Rates of treatment discontinuation because of adverse events (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade ≥ 3 AE rates were 87.0% (KRd) and 83.3% (Rd). Selected grade ≥ 3 AEs of interest (grouped terms; KRd v Rd) included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse.

scholarly journals Outcomes of Salvage Fractionated Reirradiation Combined With Bevacizumab for Recurrent High-grade Gliomas That Progressed After Treatment With Bevacizumab

2021 ◽  
Author(s):  
Hajime Yonezawa ◽  
Makoto Ohno ◽  
Hiroshi Igaki ◽  
Yasuji Miyakita ◽  
Masamichi Takahashi ◽  
...  
Keyword(s):  
Gastrointestinal Haemorrhage ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
Mutation Status ◽  
Free Survival ◽  
Not Otherwise Specified ◽  
Radiological Response ◽  
High Grade Gliomas ◽  
Grade 3

Abstract Background: This study evaluated the outcomes of reirradiation combined with bevacizumab (Bev) for patients with recurrent high-grade gliomas that progressed after treatment with Bev.Methods: Between January 2015 and September 2019, 14 patients who experienced progression after Bev treatment were treated with reirradiation consisting of 25 Gy in five fractions combined with Bev (ReRT/Bev). The isocitrate dehydrogenase (IDH) 1/2 mutation status was analysed by pyrosequencing. Results: The diagnoses of 14 patients at the time of reirradiation included six cases of glioblastoma (GBM) with IDH-wildtype, four cases of GBM with IDH-mutant, one case of anaplastic astrocytoma (AA) with IDH-wildtype, one case of AA with IDH-mutant, and one case of GBM not otherwise specified (NOS), and one case of radiologically diagnosed brainstem glioma. The median overall survival (OS) and progression-free survival (PFS) times with ReRT/Bev were 6.1 months and 3.8 months, respectively. The 6-month OS and PFS rates were 54.5% and 15.7%, respectively. The median OS and PFS did not differ significantly between patients with IDH-wildtype (N=7) and IDH-mutant (N=5) (OS: 7.3 [wildtype] vs 6.0 [mutant] months, p = 0.64; PFS: 3.8 [wildtype] vs 3.7 [mutant] months, p = 0.56). The median OS and PFS did not differ significantly between patients with a diagnosis of GBM (N=6) and those with a diagnosis of non-GBM (N=7) (OS: 9.3 [GBM] vs 6.0 [non-GBM] months, p = 0.19; PFS: 4.0 [GBM] vs 3.8 [non-GBM] months, p = 0.31). Four patients (28.6%) achieved a complete or partial radiological response and three patients (21.4%) experienced improvement after ReRT/Bev. Tumor recurrences were observed in 12 patients, including 3 (21.4%) in-field recurrence; 5 (35.7%) marginal recurrence, 3 (21.4%) out-field recurrence, and 1 (7.1%) had in-field and out-field recurrence. Grade 3/4 toxicities included leukopenia in four patients (28.6%), hypertension in three (21.4%), proteinuria in one (7.1%), and gastrointestinal haemorrhage in one (7.1%) with ReRT/Bev. Conclusions: ReRT/Bev for patients with high-grade glioma who experienced progression after Bev was effective and involved acceptable toxicities.

Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma

2017 ◽  
Vol 35 (35) ◽  
pp. 3898-3905 ◽  
Author(s):  
Martin Dreyling ◽  
Armando Santoro ◽  
Luigina Mollica ◽  
Sirpa Leppä ◽  
George A. Follows ◽  
...  
Keyword(s):  
Overall Survival ◽  
Safety Profile ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Indolent Lymphoma ◽  
Phosphatidylinositol 3 Kinase ◽  
Free Survival ◽  
Duration Of Response ◽  
Grade 3

Purpose Phosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant activity against PI3K-α and -δ isoforms, has demonstrated efficacy and a manageable safety profile in patients with indolent lymphoma. Patients and Methods In this phase II study, 142 patients with relapsed or refractory indolent lymphoma after two or more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days 1, 8, and 15 of a 28-day cycle. The primary end point was objective response rate; secondary end points included duration of response, progression-free survival, and overall survival. In addition, safety and gene expression were evaluated. Results Median age was 63 years (range, 25 to 82 years), and patients had received a median of three (range, two to nine) prior regimens. The objective response rate was 59% (84 of 142 patients); 12% of patients achieved a complete response. Median time to response was 53 days. Median duration of response was 22.6 months, median progression-free survival was 11.2 months, and median overall survival had not yet been reached. The most frequent treatment-emergent adverse events were transient hyperglycemia (all grades, 50%; grade 3 or 4, 41%) and transient hypertension (all grades, 30%; grade 3, 24%). Other grade ≥3 events included decreased neutrophil count (24%) and lung infection (15%). High response rates to copanlisib were associated with high expression of PI3K/B-cell receptor signaling pathway genes. Conclusion PI3K-α and -δ inhibition by copanlisib demonstrated significant efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory indolent lymphoma.

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