Use Of Extracorporeal Photopheresis Research Articles

The value of extracorporeal photopheresis as an immunosuppression-modifying approach in solid organ transplantation: a potential solution to an unmet medical need

Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area.

Mode of action, indications and recommendations on extracorporeal photopheresis (ECP).

Extracorporeal photopheresis (ECP) has gained importance in the treatment of several diseases. Initially introduced as a new therapeutic modality for the treatment of patients with cutaneous T-cell lymphoma, the indications for the use of ECP have expanded to include hematology and transplantation immunology. Extracorporeal photopheresis has found its place in the treatment plan of cutaneous T-cell lymphoma, systemic sclerosis, graft-versus-host disease, organ transplantation such as heart and lung, sometimes as first-line therapy and very often in combination with various systemic immunosuppressive therapies. The procedure basically consists of three steps: leukapheresis, photoactivation and reinfusion. The following article presents possible theories about the mechanism of action, which is not yet fully understood, and discusses the five most common indications for ECP treatment with corresponding therapy recommendations.

(114) Prophylactic Use of Extracorporeal Photopheresis (ecp) - A Prospective Randomized Single Center Trial

(114) Prophylactic Use of Extracorporeal Photopheresis (ecp) - A Prospective Randomized Single Center Trial

European multicenter study on the real-world use and clinical impact of extracorporeal photopheresis after heart transplantation

Aim of this study was to describe the real-world use of extracorporeal photopheresis (ECP) and assess its impact on clinical outcomes in the modern era of heart transplantation. Seven transplant centers from 5 European countries participated in this retrospective, observational, single-arm chart review study. All patients received ECP after heart transplantation in 2015 or later. Data were extracted from medical records between November 2020 and December 2021. Overall, 105 patients were enrolled and followed for an average of 2 years after initiation of ECP. Reasons to start ECP were acute cellular rejection (35.2%), rejection prevention (32.4%), mixed rejection (18.1%), and antibody-mediated rejection (14.3%). Rejection ISHLT grades improved from start to end of ECP treatment in 92% of patients treated with ECP for rejection. Of patients who started ECP to prevent rejection, 88% remained free from any rejection despite a reduction of calcineurin inhibitors. Overall survival was 95%, and no deaths were related to ECP. Safety events occurred in 18 patients, of which 13 experienced complications with venous access. This study, the largest European ECP study in heart transplantation, demonstrates that ECP can effectively be used to treat different rejection types and to prevent rejection in the modern era of immunosuppression. Patients with rejections who have received ECP have shown high response as measured by histological improvements in ISHLT classification. A high percentage of patients in the prevention group remained free from rejection despite reduction in immunosuppression, in particular calcineurin inhibitors.

Extracorporeal Photopheresis as Graft-versus-Host Disease Prophylaxis: A Randomized Controlled Trial

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole curative option for many patients diagnosed with hematologic malignancies. A major obstacle is graft-versus-host disease (GVHD), causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied treatment for GVHD, owing in part to its favorable safety profile. In contrast, reports on the use of ECP to prevent GVHD are rare, and randomized controlled trials (RCTs) are lacking. We conducted an RCT to assess whether ECP applied post-transplantation could prevent the development of GVHD within the first year of transplantation. We enrolled 157 patients (age 18 to 74 years) with a hematologic malignancy undergoing their first allo-HSCT, randomized as 76 to the intervention group and 81 to the control group. ECP was initiated directly on engraftment and was planned twice weekly for 2 weeks, then once weekly for 4 weeks. GVHD, relapse, and death were analyzed by Cox regression analysis. During the first year, 45 patients in the intervention group and 52 control patients developed GVHD (hazard ratio [HR], .82; 95% confidence interval [CI], .55 to 1.22; P=.32). There were no differences in acute or chronic GVHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GVHD between the intervention group (per-protocol; n=39 of 76) and the control group (n=77), 46% versus 68%, respectively (HR, .47; 95% CI, .27 to .80; P=.006). Relapse occurred in 15 patients in the intervention group and in 11 control patients (HR, 1.38; 95% CI, .64 to 3.01; P=.42). GVHD-free relapse-free survival, event-free survival, overall survival, and nonrelapse mortality did not differ significantly between the 2 study groups. There also was no significant difference in immune reconstitution between the 2 groups. This first intention-to-treat RCT investigating ECP as GVHD prophylaxis in allo-HSCT for hematologic malignancy does not support the use of ECP as an adjunct to standard drug-based GVHD prophylaxis.

Impact of Cryopreservation on Extracorporeal Photopheresis (ECP)-Treated Leukocyte Subsets

BackgroundExtracorporeal photopheresis (ECP) is frequently utilized in the treatment of steroid-refractory acute and chronic graft-versus-host disease (GVHD). Although the mechanism of action is not fully understood, it has been postulated that its therapeutic effect is immunologic tolerance linked to the associated apoptosis of the treated cells. Despite significant advances in allogeneic hematopoietic stem cell transplantation (HSCT), prophylaxis and treatment of GVHD remain a challenge and major limitation associated with this therapy. Use of ECP is a valuable strategy; however, it is time, cost, resource intensive, and not readily accessible. ObjectiveIn an effort to expand access to this therapy, we are investigating the use of cryopreserved ECP-treated cells. This will provide the ability to administer a significant proportion of the treatment at a facility closer to the patient's residence, thereby decreasing the number of visits to the primary treatment center with the goal of improving and expanding access to this therapy. Here we report the effects of cryopreservation on ECP-treated leukocytes. Study DesignMononuclear cells were pheresed from human patients, ECP-treated, and collected for viability and apoptotic analysis. Cells were then cryopreserved at -80°C or -150°C for 1 week, 1 month, and 3 months. Following thaw, repeat viability and apoptosis studies were performed on the leukocytes. ResultsWBC viability for freshly ECP-treated leukocytes was 84.5% ± 3.5 at 1 week, 87.3% ± 5.2 at 1 month, and 79.1% ± 1.1 at 3 months post thaw. Similar results were seen for cells frozen in cryovials. Leukocytes frozen the day after ECP treatment had 1 week and 1 month WBC viabilities of 84.0 ± 4.1 and 83.1 ± 2.1, respectively. Apoptotic potential was well preserved at 3 months, with cryopreserved ECP-treated lymphocytes being 19.2%, 44.5%, 75.5%, and 94.0% apoptotic after thaw on days 0, 1, 2, and 3 in culture, respectively. ConclusionsECP-treated leukocytes cryopreserved at -80°C or -150°C for 3 months remain viable and as capable of apoptosis as freshly treated cells. Cryopreservation of an ECP-product warrants further in vivo investigation as a strategy to facilitate access to this needed therapy.

Belumosudil Combination Therapy in Refractory Chronic Graft-Versus-Host Disease

Background: There are now 3 FDA approved oral drugs for chronic graft-versus-host disease (cGVHD) after 1-2 or more prior lines of therapy- ibrutinib, ruxolitinib and belumosudil. Encouraging overall response rates have been reported for all 3 agents; however, complete responses are rare and there are still a large number of patients who do not respond or lose the response over time. One of the approaches to overcome potential resistance to single agent use is to combine the new agents with each other or with other therapies (such as extracorporeal photopheresis (ECP), sirolimus, MMF) as there can be synergy across agents with different mechanisms of action. The 3 new drugs are all kinase inhibitors that block lymphocyte activation pathways and the production of proinflammatory cytokines. Preclinical studies showed their potential effects in cGVHD. Since the FDA approvals, it has been possible to use these drugs in various combinations for cGVHD treatment in daily clinical practice. In this retrospective review, we summarize our institution's real-world practice of using the ROCK2-inhibitor belumosudil in combination therapies since its FDA approval in July 2021. Methods: We conducted a retrospective chart review of patients treated with belumosudil in combination with other therapeutic agents at the Stanford Cancer Institute from July 2021 to July 2022. We collected descriptive statistics of standard outcomes of response as defined by the 2014 NIH Consensus Project on Criteria for Clinical Trials in cGVHD. Refractory cGVHD was defined as steroid-refractory or steroid-dependent cGVHD. Results: A cohort of 26 patients were evaluated (Table 1). The most common organ affected was skin (n = 20), followed by mouth (n = 19), eyes (n = 15) and joints/fascia (n=15). Patients were treated with a median number of 3 lines of prior therapies before initiating belumosudil. Combination therapies with belumosudil included several 3-4 drug combinations with concurrent use of ruxolitinib, ECP, prednisone, sirolimus or CNI. In instances in which belumosudil was combined with ruxolitinib, belumosudil was the add-on drug. The median follow-up period following initiation of belumosudil was 213.5 days. The overall response rate (ORR) following the addition of belumosudil was 77% (20/26). Responses to belumosudil used in combination were based on organ symptom scoring and global rating by clinician assessment according to the 2014 NIH Consensus Criteria and were seen in 85% (17/20) patients with skin involvement; 53% (8/15) patients with joint/fascial involvement, 33% (5/15) patients with eye involvement, 30% (3/10) patients with lung involvement, 11% (2/19) patients with mouth involvement, and 13% (1/8) patients with liver involvement (Table 2). No responses were seen in patients with GI (lower tract) involvement. No clinically evident adverse drug reactions occurred in the belumosudil combinations although variable dosing of the combined agents was used with the approved belumosudil dose of 200 mg po daily. Infectious adverse events occurred in 42% (11/26) of patients, consistent with the immunosuppressive effects of cGVHD therapies. Of these, 36% (5/14) was due to SARS-CoV2 infection, 29% (4/14) cytomegalovirus reactivation, 21% (3/14) bacterial infection, 7% (1/14) rhinovirus infection, and 7% (1/14) respiratory syncytial virus. The number of infection events with the new agent combination of belumosudil plus ruxolitinib was reviewed separately and was not increased over the other belumosudil combinations. No deaths have occurred in this cohort of 26 patients to date. Conclusion: In our institutional practice, administration of belumosudil in combination therapy appears safe, tolerable, and effective in patients with established, refractory cGVHD. The results of our retrospective study highlight the feasibility of the next phase of belumosudil research for combination therapy in this difficult-to-treat population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Extracorporeal photopheresis (ECP) improves overall survival in the treatment of steroid refractory acute graft-versus-host disease (SR aGvHD).

Steroid refractory acute graft-versus-host disease (SR aGvHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) has been used to treat SR aGvHD effectively and with low treatment related toxicity. In this study, we retrospectively analyzed the outcomes of 103 Steroid Refractory aGvHD (SR aGvHD) patients to identify factors associated with improved outcomes including the use of ECP. A total of 79 patients received ECP as part of their SR aGVHD treatment compared to 24 patients who did not. Both groups had similar aGVHD grade and maximum organ stage at onset of aGVHD and treatment initiation. Patients in the group that received ECP had better OS (p = 0.01), DFS (p = 0.008), lower relapse (p = 0.05) and similar NRM compared to the group that did not receive ECP. Patients that received ECP treatment also had shorter hospital stays in the first 180 days after onset of SR aGvHD (20 vs. 38 days, p = 0.03). Multivariable analysis for OS indicated patient CMV status (CMV+ versus CMV-, HR 2.34, CI 1.16-4.69), regimen intensity (Myelo vs. non-Myeloablative, HR 0.39, CI 0.20-0.75), and the use of ECP (ECP vs. no ECP, HR 0.39, CI 0.20-0.75) were associated with OS. In summary, the use of ECP in the treatment of SR aGvHD results in improved overall survival secondary to lower relapse rates compared to other therapeutic modalities that do not incorporate ECP.

Real World Use of Extracorporeal Photopheresis After Heart Transplantation - Clinical Outcomes from a Seven Centre European Study

<h3>Purpose</h3> Extracorporeal photopheresis (ECP) is recommended by different apheresis and transplant societies based on study results from 1998 and 2006 as an adjunctive therapy in prevention and treatment of acute cellular rejection (ACR) after heart transplantation (HTx). At present, however, it is also used to treat antibody mediated rejection (AMR) with and without (+/-) donor specific antibodies (DSA). The aim of this study was to describe the real-world use of ECP across European heart transplant centres and assess its impact on clinical outcomes in the modern era of heart transplantation. <h3>Methods</h3> Seven transplant centres located in five European countries participated in this retrospective, explorative, single-arm chart review study of over 90 patients. All included patients received ECP after heart transplant in 2015 or later with a follow-up period of up to two years after the last ECP treatment. Data have been extracted from the medical charts covering patient characteristics, reasons for ECP treatment, ECP treatment schedule and duration, concomitant treatments, clinical outcomes (e.g. graft dysfunctions, rejections, survival, immune system, kidney function) as well as treatment related complications and safety. <h3>Endpoints</h3> The findings of the full study analysis from the largest known multi-centre study on ECP after HTx, will be presented for ECP treatment overall, and for the three sub-groups ACR, AMR (+/- DSA), and prevention of rejection. Endpoints that will be reported will include graft and overall survival, incidence of rejections, infections and complications, changes in rejection grading, improvements in graft function, and ECP related safety data.

Extracorporeal Photopheresis in CLAD: A 15-Year Single Centre Experience

<h3>Purpose</h3> Use of extracorporeal photopheresis (ECP) in chronic lung allograft dysfunction (CLAD) extends over 25 years. Various single centre reports suggest some benefit, but unequivocal data is lacking. Methodology and changes in CLAD definitions have hindered comparisons, and uncertainty remains about ECP efficacy in current CLAD phenotypes. This study summaries our experience of ECP in CLAD, assessing outcomes and determining treatment duration. <h3>Methods</h3> A retrospective review of all patients receiving ECP for CLAD was performed. Data from legacy patients was reanalysed according to current definitions. Patients were treated with 2-cycles fortnightly, or occasionally 1-cycle weekly for 6 months depending on resources. Primary outcomes were nature of ECP response: stabilized, partial response or non-response and graft survival. Secondary endpoints include time to ECP response and the effect of CLAD phenotype shift during ECP, particularly regarding timing and development of restrictive spirometry. <h3>Results</h3> In total 369 patients commenced ECP for CLAD. Median follow-up was 27 [IQR 8.6-70.6] months. Graft stabilization was achieved in 140/369 (38%) patients. A further 85/369 (23%) of patients exhibited slowing in FEV₁ decline but failed to stabilize during the study. The remaining 144/369 (39%) demonstrated no appreciable response to ECP. Graft survival in the latter group was poorest, with 3-year survival of 18%. Among transient responders 3-year survival was surprisingly good at almost 75%, with almost all stabilized patients surviving 3 years. Patients commenced on ECP for restrictive allograft syndrome (RAS) did poorly. Bronchiolitis obliterans patients who subsequently developed restrictive features, subsequently developed ECP responses similar to RAS. A reliable prediction of lack of ECP response was evident after 106 [71 - 181] days. <h3>Conclusion</h3> ECP appears to offer a survival benefit in some CLAD patients. A sizeable minority of patients stabilized and this conferred the best prognosis. Any demonstrable effect on dFEV1 within 6 months of initiation may support ECP continuation. Should no change in dFEV1 occur in this period, treatment withdrawal should be considered. Restrictive phenotypes, developing either prior to or during ECP treatment confer a very poor prognosis.

Immunogenic and immunotolerogenic effects of extracorporeal photopheresis in high immunological risk kidney recipients. A single center case series

The immunomodulatory effects of extracorporeal photopheresis (ECP) have been used for the treatment of T-cell mediated disorders, such as rejection in organ transplantation. Currently, it is an established therapy for heart and lung rejection, but not for kidney transplantation (KT), where experience is limited. In addition, some data suggest that ECP could generate an immune response against infections, thus being an alternative for the treatment of rejection in case of active or high-risk of infection. In the present study, we analyze four cases of use of ECP as concomitant therapy in patients with KT and high risk of opportunistic infections due to the high burden of immunosuppression throughout their renal diseases. Two patients had concomitant viral infection (cytomegalovirus and BK virus, respectively) and three patients were on treatment for graft rejection. In the two patients with active viral infection, the infection was successfully controlled during ECP treatment. In all cases, ECP has been shown to be a safe procedure, without complications.

Propensity Score Matching Analysis Comparing Extracorporeal Photopheresis (ECP) Vs Best Available Therapy in Third Line or Later Treatment of Chronic Graft-Versus-Host Disease (cGVHD)

*DB and DK contributed to the work equallyBackgroundProspective randomized controlled data comparing extracorporeal photopheresis (ECP) to other treatments for chronic graft vs host disease (cGvHD) as third-line or later therapy are limited, despite its clinical benefit observed in patients (pts) who failed ≥ 2 lines of previous therapy. Our single-center experience has reported promising results, including 68.3% failure-free survival (FFS) and 85.9% overall survival (OS) at 12 months in 75 heavily pre-treated cGvHD pts treated with ECP (ASH 2021 Abstract ID 152640).The present study compared outcomes, using propensity-score matching (PSM), between ECP (“ECP group”, n=74) and a historical cohort treated with best available therapy (BAT) as third-line or later treatment from 2007 to 2021 (“BAT group”, n=132). Statistical endpoints such as FFS and OS, as well as steroid dose reduction were evaluated instead of overall response due to limited response assessment data available from retrospective chart review.Patients and methodsThe BAT group received MMF (n=71, 53.8%), prednisone (n=37, 28.0%), prednisone/cyclosporine (n=7, 5.3%), rituximab (n=7, 5.3%), and others (n=10, 7.6%). There was an imbalance in characteristics between the two groups, as expected; the ECP group had more pts with severe cGVHD (91.1% vs 20.5%; p<0.001), fewer with a previous history of acute GVHD (aGvHD: 60.8% vs 78.0%; p=0.008), and fewer on a prednisone dose ≥0.5mg/kg/day (37.8% vs. 90.5%; p<0.001). PSM analysis was applied to adjust risk factors imbalanced between groups, including cGVHD grade (mild/moderate vs severe), aGVHD history, and baseline prednisone dose (<0.5 vs. ≥ 0.5 mg/kg/day). A total of 54 pts (27 case-control pairs) were selected via PSM within 0.2 of a calliper difference, resulting in the balancing of risk factors between groups: cGVHD severity (p=0.941), aGVHD history (p=0.75) and prednisone dose ≥ 0.5 mg/kg/day (p=0.788).FFS and OS were calculated from the day of starting ECP or BAT, and were compared using Cox's hazard model. Daily prednisone dose at months 0, 3 and 6 were calculated divided by body weight (kg), and the proportions of pts on prednisone ≤ 0, 0.1, 0.2 and 0.5mg/kg/day were compared.ResultsIn the overall cohort (n=206), with a median 29 months of follow-up, 114 treatment failures (55.3%) occurred. While the non-relapse mortality (NRM) was similar in both groups, the ECP group showed a lower rate of resistance requiring therapy switch. Failure was noted in 27 ECP pts (36.4%) due to causes including resistance/intolerance requiring a switch to other therapy (n=15; 20.3%), NRM (n=11, 14.8%), and relapse (n=1; 1.4%), while 87 failures (65.9%) were noted in BAT pts due to resistance requiring a switch to other therapy (n=63; 47.7%), NRM (n=7; 5.3%), and relapse (n=17; 12.9%).In the overall cohort, the 12-month FFS was 68.3% and 32.0% in ECP and BAT groups (p<0.0001; Fig 1A), while OS was 86.2% and 82.2% in ECP and BAT groups, respectively (p=0.333; Fig 1B). In the PSM cohort (n=54), the ECP group showed a survival benefit at 12 months: FFS was 65.8% in the ECP group vs. 30.5% in the BAT group (p=0.00226; Fig 2A), and OS was 76.6% in the ECP group vs. 67.1% in the BAT group (p=0.0977; Fig 2B).Multivariate analysis in the PSM cohort confirmed that ECP was superior to BAT for FFS (p=0.024, HR 0.317 [0.117-0.859]) when adjusted for other risk factors including cGVHD severity, aGvHD history, age, HCT-CI score and prednisone dose ≤0.5mg/kg/day.Prednisone doses were gradually reduced over time; the median doses of prednisone at months 0, 3, and 6 were 0.35, 0.22 and 0.11 mg/kg/day, respectively, in the ECP group vs. 0.96, 0.24 and 0.19mg/kg/day in the BAT group. ECP also showed better kinetics of steroid dose reduction over time; the proportions of pts who discontinued prednisone at months 0, 3 and 6 were 16.2, 17.6% and 32.4% in ECP group vs. 0.8%, 0% and 2.5% in BAT group (Fig 3). The differences in the proportion of pts (delta) who discontinued prednisone in the ECP vs. BAT groups were 15.4%, 17.6% and 29.9% at 0, 3, and 6 months, respectively.ConclusionIn the current study using PSM analysis, use of ECP was associated with a superior FFS to BAT when used as third-line or later therapy in cGVHD patients who failed at least 2 lines of previous therapy. Use of ECP also allowed for better steroid tapering in comparison to BAT. [Display omitted] DisclosuresPatriquin: Alexion: Consultancy, Honoraria, Speakers Bureau; BioCryst Pharmaceuticals: Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company. Kim: Novartis: Consultancy, Honoraria, Research Funding; Paladin: Consultancy, Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria.

Epi-O-06 - Extracorporeal photopheresis in varying mycosis fungoides and Sézary syndrome stages: race-based differences in treatment utilization and response

<h3>Background:</h3> Black patients can face a higher incidence and poorer prognosis from cutaneous T-cell lymphoma (CTCL) compared to their white counterparts yet race is not a known factor in the treatment of CTCL. The significance of race, particularly in the treatment of early-stage CTCL using extracorporeal photopheresis (ECP), is not well understood. <h3>Objective:</h3> To characterize race-based and stage- based differences in ECP utilization and response among adults with mycosis fungoides and Sézary syndrome. <h3>Methods:</h3> A 10-year retrospective chart review was performed at a single tertiary referral center institution. <h3>Results:</h3> Among total 42 qualifying CTCL patients that received, 57.1% were female, 47.6% identified as black, and 54.7% presented with early-stage CTCL (Stage IA–IIA). There were no race-based differences in the number of systemic therapies trialed before ECP (p=0.8), use of ECP as 1st-line treatment (p=0.5), number of ECP treatments (p=0.4965), or use of concomitant medications (e.g. interferon, oral retinoids). White patients began ECP sooner than black patients following CTCL diagnosis (median 16 vs 4 months; p=0.08). Black patients were significantly more likely to face progressive disease following ECP (p=0.04) and had a shorter duration of response (16.1 vs 36.5 months; p=0.0455). <h3>Limitations:</h3> This was a retrospective study. <h3>Conclusion:</h3> There are race-based differences in ECP use and disease progression among adults with CTCL. Future research may investigate the source of these disparities, be they attributable to biologic differences in disease or differential treatment prescription.

Tre-P-21 - Extracorporeal photopheresis during the COVID-19 pandemic: experience in Argentina

Background:Patients with primary cutaneous lymphoma receive immunosuppressive therapy for long term disease control. Both cutaneous lymphoma and immunosuppressive treatment can contribute to the development of more severe COVID-19 complications. The real challenge during the COVID-19 pandemic remains the management of the advanced and aggressive forms of cutaneous lymphomas, including late-stage mycosis fungoides (MF) and Sézary syndrome (SS). Extracorporeal photopheresis (ECP) is one of those treatments. ECP is considered high risk therapy according to the United States Cutaneous Lymphoma Consortium recommendations for treatment of cutaneous lymphomas during the COVID-19 pandemic because it may require travel to the clinic or hospital.Methods:In this cross-sectional retrospective study, data of patients with MF or SS who received ECP treatment were collected. ECP consisted of a two-session cycle every two to four weeks. In our group we did not carry out prophylactic interruption of the therapy, once started. In patients with stable disease (SD) or partial response (PR), ECP was administered every 4 weeks, until a 6-week maximum interval was reached, and the response maintained. During the study period, the frequency of treatments was decreased, especially for patients with severe comorbidities and/or older age. The associated therapy was considered individually, depending on the extension of the disease, comorbidities, and adverse effects of each agent.Results:16 patients with cutaneous lymphoma received ECP (9 (56%) with SS and 7 (44%) with MF). Their median age at diagnosis was 63 (57–67) years. The median number of treatments before ECP was 2 (1–3), which was typically either phototherapy or systemic corticosteroids. Regarding the associated treatment during ECP and pandemic, INF and retinoids were the first-choice treatments. In the MF group 3 patients (2 PR and 1 relapse) required additional therapy with acitretin and topic corticosteroids. In the SS group 5 patients (1 PR, 3 progressive disease and 1 relapse) received concomitant t treatment with INF alfa 2b, bexarotene and electron beam; the relapsed patient underwent mono chemotherapy. Three patients were infected with SARS-CoV-2, all of them were from the SS group, the contagion was outside the hospital environment. Two of the patients who developed COVID infection died.Conclusion:For patients with advanced forms of LCCT, who usually have multiple risk factors for a severe course of SARS-CoV-2 infection therapy. The critical patient subset includes those with advanced disease, who require treatment with polychemotherapy, ECP and checkpoint inhibitors. Treatment decisions should be made on an individual basis. In our experience, the continuous use of ECP during the pandemic did not increase the risk of contagion.

Use of Extracorporeal Photopheresis (ECP) in the Treatment of Patients with Cutaneous T-Cell Lymphoma (CTCL), 2010-2015

Introduction: Extracorporeal photopheresis (ECP) is an immunotherapeutic procedure approved in the US for the treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL); in Europe, ECP is also used for the treatment of additional conditions such as graft versus host disease (GvHD), organ transplant rejection, and selected autoimmune diseases. Developments in immune system/cell biology and publications of real-world ECP data have advanced the understanding of the effects of ECP as a cell-based immunomodulator. The National Comprehensive Cancer Network (NCCN) CTCL Treatment Guidelines as well as the European Organization for Research and Treatment of Cancer (EORTC) recommend ECP as systemic therapy, which can be used in combination with interferon and/or a retinoid. The objective of this study was to analyze real-world use of ECP in the treatment of patients with CTCL in the US between 2010 and 2015.Methods: A retrospective analysis was conducted using the Truven Health MarketScan® Commercial and Medicare Supplemental claims databases (2010-2015). Patients with CTCL undergoing systemic treatment, with 9 months continuous enrollment (3 months prior to and 6 months after the initiation of systemic treatment), were included. Patient demographics and clinical characteristics by type of systemic therapy (ECP vs non-ECP) were evaluated, as well as most prevalent comorbid conditions. ECP use, frequency, and duration, as well as proportions of patients using ECP as mono- or combination therapy, were described. Propensity score matching and multivariate regression analyses were conducted to compare key outcomes such as length of stay (LOS), hospitalization cost, and total cost associated with use of ECP while controlling for covariates.Results: Of the 2092 patients with CTCL who were receiving systemic treatment (12.6% of the total number of patients with CTCL [N=16,574]), 1106 patients were included who met the continuous enrollment criterion (mean age: 57.4 years; males: 57.1%). The top comorbid conditions were psoriasis (21.8%), organ transplant (12.2%), GvHD (7.5%), and scleroderma (2.5%). Of the 1106 eligible patients, 117 patients (10.6%) received ECP, with an average treatment duration of 13.6 months. ECP was used as monotherapy in 76 patients (65.0%) and combination in 41 patients (35%), mostly with interferon and/or a retinoid. Compared with non-ECP-treated patients (n=989), ECP-treated patients (n=117) had a significantly higher Charlson Comorbidity Index (CCI) score (2.6 vs 2.2, P <0.05), rate of organ transplant (49.6% vs 7.8%, P <0.05) and occurrence of GvHD (41.9% vs 3.4%, P <0.05). Generalized linear models (GLMs) were used to compare key outcomes (all-cause and CTCL-related LOS, hospitalization cost, and total cost) during the follow-up period, based on the pool of ECP-treated patients and propensity score matched non-ECP-treated patients. Results of GLMs indicated that ECP was associated with numerically lower all-cause and CTCL-related total LOS, all-cause hospitalization cost, and all-cause total cost while controlling for covariates.Conclusions: Results from this US claims-based analysis of recent data demonstrated that ECP was used as a systemic treatment in 10.5% of patients with CTCL, with an average duration of 13.6 months. ECP was used twice as often as monotherapy compared with combination uses. CTCL patients treated with ECP appeared to have increased clinical complexity, with higher CCI scores, rates of organ transplant, and occurrence of GvHD. However, patients treated with ECP had lower all-cause LOS as well as numerically reduced hospitalization and total costs. DisclosuresLing:Mallinckrodt Pharmaceuticals: Consultancy. Huang:Mallinckrodt Pharmaceuticals: Employment. Mitri:Mallinckrodt: Employment. Pham:University of California, School of Pharmacy: Employment; Mallinckrodt Pharmaceuticals: Employment. Lovelace:Mallinckrodt Pharmaceuticals: Employment. Knobler:Mallinckrodt Pharmaceuticals: Consultancy. Gao:Mallinckrodt Pharmaceuticals: Consultancy, Employment.

Long-Term Outcome of Patients Receiving Extracorporeal Photopheresis for Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies: Results from an Observational Study on 106 Patients

Graft-versus-host disease (GVHD), and complications of its treatment are the major causes of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Even with the use of standard GVHD prophylaxis with classical administration of Anti-thymocyte globulin (ATG), calcineurin inhibitors (CNIs) and methotrexate, the incidence of acute and chronic forms of GVHD remains not negligible. Extracorporeal photopheresis (ECP) has shown very promising results as curative strategy for GVHD but also when used prophylactically.The primary objective of this observational study was to perform an exhaustive description concerning patients receiving ECP after steroid resistance for either acute or chronic GVHD following allo-HCT, secondary objectives were to evaluate the efficacy and long-term outcomes.We included 106 patients who underwent allo-HCT between years 2001 and 2016, 65 (61%) were males, median age at allo-HCT was 52 years (20-67). Major diagnoses were acute leukemias (N=48, 45%), myelodysplastic syndromes (N=18, 17%) and multiple myeloma (N=12, 11%). Before transplantation, 56 (53%) patients were in complete remission or in chronic phase. Donors were identical siblings in 51% of patients, matched unrelated in 24%, mismatched unrelated in 24% and haploidentical in 1%. Cells source was peripheral blood in 65%, bone marrow in 27% and cord blood in 8%. Conditioning regimens were of reduced intensity in 62% and myeloablative in 38%. ATG was used during conditioning in 67% of patients. GVHD prophylaxis consisted on cyclosporine A (CsA) alone in 22 (21%) patients, CsA + mycophenolate mofetil in 29 (27%), CsA + methotrexate in 28 (26%), the rest received other combinations.In acute GVHD, first treatment consisted in methyl-prednisolone 2mg/Kg/day in combination with CNIs; and in chronic GVHD, it was methyl-prednisolone 0.5 - 1 mg/Kg/day + CNIs. ECP was performed using peripheral venous access. The ECP used the CELLEX system from Therakos®. ECP was initiated after transplantation either for acute GVHD [N=25 (24%), 12 grade III and 13 grade IV] affecting skin alone (N=5), gut alone (N=12), gut + liver (N=8); or for chronic GVHD [N=81 (76%), 15 (14%) limited and 66 (62%) extensive]. A total of 3300 ECP sessions were performed, majority (N=91, 85%) were twice a week; the median number of sessions/patient was 22 (min: 2, max: 132) for a median duration of 2.5 months (range: 0.5-48). ECP response evaluation was assessed after 4 weeks of treatment, patients were considered responding to ECP if more than 50% resolution of clinical GVHD manifestation of the organ involved was registered.Among the 25 patients treated for acute GHVD, one was not evaluable because of disease progression and early death, 16/24 (67%) were responders to ECP and 8/24 (33%) were not responders and died later from GVHD associated to other complications. Among the 81 patients with chronic GVHD, 63/81 (78%) were responders and had tapering of ECP, the remaining 18 patients had limited response were associated to infection, had other complications and died later. Of note, in both forms of acute and chronic GVHD, responding patients had more skin or mucosa forms whereas non-responding patients has more organ-involved forms especially liver and gut.After a median follow-up of 21 months, 52 (49%) patients are alive and 54 (51%) died with 39 (24%) from TRM causes (26 of them from GVHD) and 13 (26%) from relapse. Patients with acute GVHD had a median OS of 6 months with a survival probability at 2 years of 35% [95%CI: 14-56], those with chronic GVHD had a median OS of 72 months with a survival probability at 2 years of 68% [95%CI: 56-78]. The cumulative incidence of relapse for the whole population at 2 years was 16.7% (95% CI: 10-24), when stratifying according to the GVHD group, patients with chronic GVHD had lower relapse rate at 2 years with 12.6% (95% CI: 6-21) versus 31% (95% CI: 13-52) for those with acute GVHD, p=0.05.In conclusion, we confirm that ECP is an effective treatment for GVHD with overall response rate of more than 74%. Interestingly, we observed a low relapse incidence in patients receiving ECP for longer time as in the case of chronic GVHD, which could be related to the GVL effect itself but also a possible involvement of the ECP. As patients with advanced phase of GVHD were poor responders, we suggest that an early use of ECP in the acute phase of the inflammation before organ damage, could lead to optimal results. [Display omitted] DisclosuresNicolini:Incyte Biosciences: Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; ARIAD: Honoraria, Speakers Bureau.

Second Line Systemic Treatments Including Extracorporeal Photopheresis Among Patients with Chronic Graft Versus Host Disease (cGVHD) in the United States, 2009-2016

Introduction: Extracorporeal photopheresis (ECP) is a cell-based immunomodulatory therapeutic procedure approved by the FDA for cutaneous T-cell lymphoma (CTCL) among individuals who have not been responsive to other forms of treatment in the United States (US). As clinical evidence accumulated over the years, Centers for Medicare & Medicaid Services (CMS) issued several Medicare National Coverage Decisions (NCDs) for coverage of ECP in patients with acute cardiac allograft rejection or chronic graft versus host disease (cGVHD), who are, refractory to standard immunosuppressive drug treatment. In contrast, per British Committee for Standards in Haematology (BCSH) guidelines on treatment of cGVHD, ECP is recommended as the first option over other 2nd-line systemic treatments including rapamycin (mTOR) inhibitors, pentostatin, rituximab, and imatinib. The objective of this analysis was to describe real-world use of ECP in patients with cGVHD in the US between 2009 and 2016.Methods: A retrospective analysis was conducted using the Truven Health MarketScan® Commercial and Medicare Supplemental claims databases (2009-2016). Adult (≥18 years) cGVHD patients receiving 2nd-line systemic treatments, with continuous health plan enrolment 3 months prior to first cGVHD diagnosis (i.e., baseline period) and 6 months following the initiation of 2nd-line systemic treatment were included. Patient demographic and clinical characteristics were summarized by type of 2nd-line systemic treatment (ECP vs. non-ECP). In addition, treatment patterns including the time from cGVHD diagnosis to initiation of 2nd-line systemic treatment, duration of ECP treatment (ie, time from initiation to end of ECP treatment), and ECP use (proportion of patients receiving ECP treatment among those receiving 1 of the 5 2nd-line systemic treatments) by year were reported. Annual per person all-cause cost for cGVHD patients for emergency room (ER) visits, office visits, and inpatient visits incurred after receiving 2nd-line systemic treatment (ie, the follow-up period) were also reported.Results: Of the 3086 adult cGVHD patients, 663 (21.5% of patients with cGVHD) patients had ≥2 claims for 2nd-line systemic treatments, of which 464 met the continuous enrollment criterion and were included in the study (mean age=49.7 years; 60.1% males). The most commonly reported underlying conditions at baseline were bone marrow transplant (268 [57.8%]), stem cell transplant (280 [60.4%]) and CTCL (25 [5.4%]). The average time from first cGVHD diagnosis to initiation of 2nd-line systemic treatment was 5.4 months. Among patients receiving 2nd-line systemic treatments, 210 (45.3%) received ECP treatment for an average duration of 11.1 months. ECP and non-ECP patients were similar in terms of demographic and clinical characteristics, with organ transplant as the most common underlying condition during the baseline period. As the number of cGVHD patients increased from 16 in 2009 to 100 in 2016, ECP use increased from 31.3% in 2009 to 54.0% in 2016. The total annual all-cause per patient cost was $190,148, including $4619 for ER visits, $8,673 for office visits, and $176,856 for hospitalizations during the follow-up period.Conclusions: Results from the latest US commercial administrative claims data pointed to an increase rate of cGVHD between 2009 and 2016. Of the 464 study patients with cGVHD, 2nd-line systemic treatment was initiated 5.4 months following the first diagnosis of cGVHD. As the number of cGVHD patients increased the rate of ECP use increased over time as well. During the study period, ECP was used by 45.3% of study patients with average duration of 11.1 months. In addition, high economic burden was reported among cGVHD patients receiving 2nd-line systemic treatments. DisclosuresJoshi:Pharmerit International: Employment; Mallinckrodt Pharmaceuticals: Research Funding. Luo:Mallinckrodt Pharmacueticals: Research Funding; Pharmerit International: Employment. Huang:Mallinckrodt Pharmaceuticals: Employment. Mitri:Mallinckrodt: Employment. Lovelace:Mallinckrodt Pharmaceuticals: Employment. Pham:University of California, School of Pharmacy: Employment; Mallinckrodt Pharmaceuticals: Employment. Gao:Mallinckrodt Pharmaceuticals: Consultancy, Employment.

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment.

Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection.

European dermatology forum - updated guidelines on the use of extracorporeal photopheresis 2020 - part 1.

BackgroundFollowing the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multi‐disciplinary setting. It has confirmed recognition in well‐known documented conditions such as graft‐versus‐host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease.Materials and methodsIn order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added.Results and conclusionThese updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines are divided in two parts: PART I covers cutaneous T‐cell lymphoma, chronic graft‐versus‐host disease and acute graft‐versus‐host disease while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatrics practice, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.

European dermatology forum: Updated guidelines on the use of extracorporeal photopheresis 2020 – Part 2

BackgroundFollowing the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well‐known documented conditions such as graft‐vs.‐host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease.Materials and methodsIn order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added.Results and conclusionThese updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines were divided into two parts: PART I covers Cutaneous T‐cell lymphoma, chronic graft‐vs.‐host disease and acute graft‐vs.‐host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn’s disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.