Exceptional responders to abexinostat (ABX) plus pazopanib (PAZ) in pretreated renal cell carcinoma (RCC) and other solid tumors: Long-term follow-up of a phase 1b study.

3022 Background: We previously reported the initial phase 1b study results of PAZ + ABX, a potent pan-HDAC inhibitor, demonstrating acceptable toxicity profile and encouraging anti-tumor activity (Aggarwal et al. JCO 2017). We report the long-term follow up of exceptional responders and additional correlative analyses associated with clinical outcomes. Methods: Key efficacy endpoints included objective response rate and duration of response. Peripheral blood histone acetylation, HDAC expression, and plasma VEGF levels were analyzed and associated with clinical outcomes. Results: 51 pts (RCC subset; N = 22) were enrolled between June 2012 and October 2015. 10 pts (20%) had experienced disease progression on prior PAZ; 59% had received any prior VEGF-targeting therapy. 9 evaluable pts (18%) (N = 6 RCC; 2 thyroid; 1 mesothelioma) achieved partial tumor response (PR), of which 6 had prior progression on VEGF-targeting therapy. 7/10 (70%) of pts with prior disease progression on PAZ monotherapy had reduction in tumor burden on study. The median duration of response was 9.1 months (range 1.2 to 70+), and clinical benefit rate (PR or stable disease > 6 months) was 33%. Five treatment-refractory pts achieved durable PRs lasting for > 2 years duration, and one previously PAZ-refractory patient with RCC remains on treatment with ongoing PR for > 6 years. Higher HDAC2 expression was associated with prolonged progression-free survival (median PFS 5.9 vs. 3.5 months, log-rank p = 0.02). Induction of histone acetylation on ABX lead-in treatment was associated with subsequent time to progression (p = 0.002). On-treatment plasma VEGF levels were inversely correlated with PBMC histone acetylation (p = 0.02). Conclusions: Markedly durable responses with PAZ + ABX are achievable, including in pts with PAZ- and VEGF-refractory RCC and other solid tumor malignancies. Host factors including HDAC expression and acetylation status may identify those most likely to benefit. A randomized phase 3 study is underway of PAZ + ABX as a first- or second-line therapy in pts with locally advanced or metastatic RCC (RENAVIV; NCT03592472). Clinical trial information: NCT01543763.

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429 Long-term analysis of MASTERKEY-265 phase 1b trial of talimogene laherparepvec (T-VEC) plus pembrolizumab in patients with unresectable stage IIIB-IVM1c melanoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0429 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A454-A454

Author(s):

Georgina Long ◽

Reinhard Dummer ◽

Douglas Johnson ◽

Olivier Michielin ◽

Salvador Martin-Algarra ◽

...

Keyword(s):

Pigment Cell ◽

Objective Response ◽

Stage Iiib ◽

List Type ◽

Talimogene Laherparepvec ◽

Unresectable Stage ◽

Long Term Follow Up ◽

Phase 1B

BackgroundPrevious findings from the MASTERKEY-265 phase 1b study showed that the combination of T-VEC and pembrolizumab was well tolerated and produced a high complete response (CR) rate of 43% in patients with advanced melanoma.1 The 3-year progression-free survival (PFS) and overall survival (OS) rates at that time were 53.6% and 71%, respectively. Here, we report the results of the long-term follow-up efficacy analyses.MethodsThe MASTERKEY-265 phase 1b trial (NCT02263508) was an open-label, single-arm study that enrolled patients who had unresectable, stage IIIB-IVM1c melanoma with injectable, measurable lesions and no prior systemic treatment. T-VEC was administered intralesionally at the approved dosing starting day 1 of week 1. Pembrolizumab (200 mg) was administered intravenously Q2W beginning on day 1 of week 6. The maximum treatment period was 2 years. The primary endpoint was dose-limiting toxicities; key secondary endpoints included objective response rate and PFS per modified irRC, OS, and safety.ResultsAs of the data cutoff (Mar 2, 2020), all 21 patients enrolled were off treatment; 6 died and 15 are in long-term follow-up. The median follow-up time was 58.6 months (range: 1.4–61.6). The CR rate remained 43% (9/21 patients). Twelve of the 13 responders (92.3%) are still in response, including all 9 patients with a CR. Median duration of response was not reached (range: 2.8+–54.3+ months). Median PFS and OS were not reached at the data cutoff. KM estimates of 4-year PFS and OS rates were 55.9% and 71.4%, respectively, which have held stable since the 3-year analysis. Patients who achieved a CR or partial response had better OS (p=0.0056) compared to those who did not respond. Median OS for non-responders was 24.4 months and was not reached for responders. No additional safety signals were detected.ConclusionsAt almost 5 years of follow-up, median PFS and OS were not reached for patients treated with the combination of T-VEC and pembrolizumab in this phase 1b study of unresectable metastatic melanoma. 92% of responders remained in response with improved OS observed in responders compared with non-responders. The corresponding randomized phase 3 trial has completed enrollment and is currently ongoing.Trial RegistrationNCT02263508Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.ReferenceLong G, Dummer R, Andtbacka R, et al. Follow-up analysis of MASTERKEY-265 Phase 1b (ph1b) trial of talimogene laherparepvec (T-VEC) in combination (combo) with pembrolizumab (pembro) in patients (pts) with unresectable stage IIIB–IVM1c melanoma (MEL). Pigment Cell Melanoma Res 2019;32:133–134.

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Balloon-expandable stents for treatment of symptomatic middle cerebral artery stenosis: Clinical outcomes during long-term follow-up

Interventional Neuroradiology ◽

10.1177/1591019918786515 ◽

2018 ◽

Vol 24 (6) ◽

pp. 666-673 ◽

Cited By ~ 3

Author(s):

Sung Hyun Baik ◽

Hyo Sung Kwak ◽

Gyung Ho Chung ◽

Seung Bae Hwang

Keyword(s):

Middle Cerebral Artery ◽

Clinical Outcomes ◽

Cerebral Artery ◽

Reperfusion Therapy ◽

Stent Insertion ◽

Recurrence Rates ◽

Long Term Follow Up ◽

Ischemic Events

Background Insertion of a balloon-expandable stent (BES) in patients with symptomatic intracranial atherosclerosis is a treatment option for reperfusion therapy. In this study, we retrospectively reviewed clinical outcomes during long-term follow-up after insertion of balloon-expandable stents in patients with symptomatic middle cerebral artery (MCA) stenosis. Methods Institutional review board approval was obtained for retrospective review of patient data. Thirty-four patients (15 men, 19 women; median age, 67.5 years) with symptomatic MCA stenosis underwent balloon-expandable stent insertion between June 2008 and December 2010. Patient records were reviewed for angiographic findings and clinical outcomes during long-term follow-up. Results Of these patients, 22 presented with acute ischemic stroke with underlying MCA atherosclerosis and had good clinical outcomes (modified Rankin Scale score (mRS): 0–2) after reperfusion therapy. Indications for stenting for the remaining 12 patients were recurrent transient ischemic attacks (TIAs) refractory to medical therapy and MCA stenosis greater than 70%. During the poststenting follow-up period, which ranged from 61 to 108 months (median, 67.5 months), a TIA occurred in five patients. Of these five patients, one experienced a complete reocclusion of the MCA stent, and three had symptomatic restenosis. The remaining 29 patients did not experience any further ischemic events or restenosis during the follow-up period. Conclusions In our study, treatment with balloon-expandable stents in patients with symptomatic MCA stenosis resulted in low recurrence rates for both ischemic events and restenosis during long-term follow-up.

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Long-term follow-up: no effect of therapeutic vaccination with HIV-1 p17/p24:Ty virus-like particles on HIV-1 disease progression

Vaccine ◽

10.1016/s0264-410x(02)00102-0 ◽

2002 ◽

Vol 20 (17-18) ◽

pp. 2343-2347 ◽

Cited By ~ 18

Author(s):

Catharina E.A. Lindenburg ◽

Ineke Stolte ◽

Miranda W. Langendam ◽

Frank Miedema ◽

Ian G. Williams ◽

...

Keyword(s):

Disease Progression ◽

Therapeutic Vaccination ◽

Virus Like Particles ◽

Long Term Follow Up ◽

Hiv 1

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COVID-19 and hematologic diseases: Risk factors and long-term follow-up of CHRONOS19 Registry.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18715 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18715-e18715

Author(s):

Kristina Zakurdaeva ◽

Olga A. Gavrilina ◽

Anastasia N. Vasileva ◽

Sergei Dubov ◽

Vitaly S. Dubov ◽

...

Keyword(s):

Risk Factors ◽

Mechanical Ventilation ◽

Disease Progression ◽

Primary Endpoint ◽

Acute Leukemias ◽

Risk Of Death ◽

All Cause Mortality ◽

Long Term Follow Up

e18715 Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and non-malignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days – 17%; 80% due to COVID-19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis – ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, non-malignant) – with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 – 4%, disease progression on Day 90 detected in 13(7%) pts; 180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day all-cause mortality in pts with hem disease was higher than in general population with COVID-19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. [Table: see text]

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Incidence of response and long-term follow-up in patients with hairy cell leukemia treated with recombinant interferon alfa-2a [see comments]

Blood ◽

10.1182/blood.v75.4.839.839 ◽

1990 ◽

Vol 75 (4) ◽

pp. 839-845 ◽

Cited By ~ 67

Author(s):

E Berman ◽

G Heller ◽

S Kempin ◽

T Gee ◽

LL Tran ◽

...

Keyword(s):

Disease Progression ◽

Hairy Cell Leukemia ◽

Interferon Alfa ◽

Hairy Cell ◽

Cell Leukemia ◽

Minor Response ◽

Recombinant Interferon ◽

Long Term Follow Up

Abstract Thirty-five evaluable patients with hairy cell leukemia (HCL) were treated with recombinant interferon alfa-2a (rIFN-alpha 2a), given at a dose of 3 X 10(6) units (U) intramuscularly (IM) daily for 6 months followed by 3 X 10(6) U IM three times a week for an additional 18 months in a single institution study. All treatment was stopped after 24 months. Sixty-nine percent of patients achieved a partial response, 11% a minor response, and 3% (one patient) had stable disease. Six patients (17%) did not respond to rIFN-alpha 2a. Two patients (6%) achieved a response but later progressed on treatment. A total of 23 patients completed 2 years of treatment and are evaluable for long-term follow-up at a median of 20 months postcompletion of therapy (range 9 to 32 months). Eleven patients (48%) have had progression of their disease at a median of 10 months (range .5 to 25 months) after treatment was discontinued. Statistical analysis of pretreatment patient characteristics did not reveal any factor(s) associated with a high probability of responding to rIFN-alpha 2a; however, analysis of post-treatment variables measured after 2 years of treatment suggested that a low platelet count was associated with a high rate of disease progression. These findings are compared with other published trials using rIFN-alpha 2b, a similar but not identical rIFN preparation. We conclude that while rIFN-alpha 2a has a high overall response incidence, the rate of disease progression after therapy is discontinued approaches 50%, and that a subset of patients can be identified who are at high risk for recurrence after completing 2 years of treatment.

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Long‐term follow‐up comparison of two different bi‐layer dermal substitutes in tissue regeneration: Clinical outcomes and histological findings

International Wound Journal ◽

10.1111/iwj.13381 ◽

2020 ◽

Vol 17 (5) ◽

pp. 1545-1547

Author(s):

Uberto M. Giovannini ◽

Luc Teot

Keyword(s):

Clinical Outcomes ◽

Tissue Regeneration ◽

Histological Findings ◽

Dermal Substitutes ◽

Long Term Follow Up

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Defibrillation threshold testing at the time of implantable cardioverter defibrillator implantation does not predict clinical outcomes during long-term follow up: a meta-analysis

European Heart Journal ◽

10.1093/eurheartj/eht308.p1399 ◽

2013 ◽

Vol 34 (suppl 1) ◽

pp. P1399-P1399

Author(s):

N. Patel ◽

S. Stavrakis

Keyword(s):

Implantable Cardioverter Defibrillator ◽

Clinical Outcomes ◽

Meta Analysis ◽

Defibrillation Threshold ◽

Cardioverter Defibrillator ◽

Defibrillation Threshold Testing ◽

Long Term Follow Up ◽

Threshold Testing

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A Long-Term Follow-up Report on Autologous Hematopoetic Cell Transplant (AuHCT) for Patients with Hodgkin Lymphoma — Limited Utility of Post-Transplant Surveillance Computerized Axial Tomography (CAT scan) and/or PET Scan,

Blood ◽

10.1182/blood.v118.21.4205.4205 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4205-4205

Author(s):

Henry C. Fung ◽

Sunita Nathan ◽

Neel B. Shah ◽

John J. Maciejewski ◽

Elizabeth Shima Rich ◽

...

Keyword(s):

Disease Progression ◽

Hodgkin Lymphoma ◽

Pet Scan ◽

Late Relapse ◽

Cell Transplant ◽

Post Transplant ◽

Cat Scan ◽

Long Term Follow Up

Abstract Abstract 4205 Background: Autologous Hematopoetic Cell Transplant (AuHCT) is the treatment of choice for patients with relapsed or refractory Hodgkin Lymphoma. Approximately 40–60% of patients achieve a durable response and possible cure after the transplant with progressive disease accounts for most of the treatment failures. CAT scan +/− PET scan are usually performed before AuHCT and repeated post-transplant to assess responses. As part of the long term follow-up; post-transplant surveillance CAT scan +/− PET scan are often performed with intent to detect early disease progression and possible early intervention. Here, we attempt to evaluate the utility of this approach by examining the patterns of treatment failures for patients with Hodgkin Lymphoma who received AuHCT. Patients/Methods: A retrospective chart review was performed. Between 01/94 and 12/06, 55 consecutive patients with refractory or relapsed Hodgkin Lymphoma underwent autologous HCT at our institution. All patients underwent a CAT scan and FDG-PET before AuHCT and approximately 2–3 months following the transplant to evaluate the response to HCT. As part of the long-term follow-up; post-transplant surveillance CAT scan were performed every 3–6 months for 2–3 years, then every 6–12 months up to 5 years post-transplant. Results: A total of 55 patients were followed post autologous HCT. The median age at HCT was 32 (ranging from 15–66); 27 were male. Seventeen patients had primary progressive HL and 38 had relapsed HL. Eighteen patients had extra-nodal disease at disease progression. With a minimal follow-up of 4 years (range 4 to 7 years) for living patients; 40 patients are alive and well with no evidence of disease. Thirteen patients developed disease progression after transplant at a median of 3 months (range 0 – 32 months) post-HCT. All the disease progression developed within the first 7 months after transplant except 2 who developed late relapse 28 and 32 months post-HCT. Fifteen patients died with 10 from progressive disease and 5 from non-relapse causes: auto accident: 1, breast cancer (incident diagnosed of late recurrent Hodgkin lymphoma): 1, AML:1 and 2 from chronic graft versus host disease after salvage allogeneic HCT. All 55 patients underwent PET scan evaluation 2–3 months after HCT to evaluate post-HCT responses. Twenty-nine patients had no evidence of PET activity post transplant, while 26 patients had evidence of activity. While there were 2 subsequent progressions in the PET negative group (1 of them was a late relapse), there were 9 progressions in the PET positive group. The 5-years estimated survival was 65%. Conclusion: In summary: 1) Most of the disease progressions after AuHCT for relapsed and refractory Hodgkin Lymphoma occurred within the first seven months after the transplant and were associated with abnormal first post-transplant CT +/− PET scan. Thus, the utility of long term surveillance radiological studies is very limited and is not recommended. 2) With longer follow-up, long-term complications including second cancer replace disease as the primary cause of treatment failure. This underscores the importance of long-term follow-up for HCT long-term survivors. Disclosures: No relevant conflicts of interest to declare.

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