Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Research Articles

Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary analysis of the Ro-CHOP phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT01796002) established that romidepsin (Ro) plus cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) did not yield an increased efficacy compared with CHOP alone as first-line treatment of peripheral T-cell lymphoma. We report the planned final analysis 5 years after the last patient enrolled. With a median follow-up of 6 years, median progression-free survival (PFS) was 12.0 months compared with 10.2 months (hazard ratio [HR], 0.79 [95% CI, 0.62 to 1.005]; P = .054), while median overall survival was 62.2 months (35.7-86.6 months) and 43.8 months (30.1-70.2 months; HR, 0.88 [95% CI, 0.68 to 1.14]; P = .324) in the Ro-CHOP and CHOP arms, respectively. In an exploratory analysis, the median PFS in the centrally reviewed follicular helper T-cell lymphoma subgroup was significantly longer in the Ro-CHOP arm (19.5 v 10.6 months, HR, 0.703 [95% CI, 0.502 to 0.985]; P = .039). Second-line treatments were given to 251 patients with a median PFS2 and OS2 after relapse or progression of 3.3 months and 11.5 months, respectively. Within the limits of highly heterogeneous second-line treatments, no specific regimen seemed to provide superior disease control. However, a potential benefit was observed with brentuximab vedotin in association with chemotherapy even after excluding anaplastic large-cell lymphoma subtype or after adjusting for histology and international prognostic index in a multivariate model (HR for PFS, 0.431 [95% CI, 0.238 to 0.779]; P = .005).

Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study.

We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial. Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis. MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; P < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; P < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% v 88.9%; P = .013) and at EOI (93.1% v 86.7%; P = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; P = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% v 16.0% in those receiving CHOP; P < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% v G-CHOP, 7.0%; R-CVP, 21.7% v G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse. MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.

Past, present and future therapeutic approaches in nodal peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCL) encompass over 30 different entities and although they share post-thymic T- or NK-cell derivation, the disease biology and genomic landscape are very diverse across subtypes. In Western populations, nodal PTCL are the most frequently encountered entities in clinical practice and although important achievements have been made in deciphering the underlying biology and in therapeutic advances, there are still large gaps in disease understanding and clinical scenarios in which controversy over best practice continues. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)- based chemotherapy continues to be the 'standard' treatment, with the addition of brentuximab vedotin (BV) in the combination CHP (cyclosphosphamide, doxorubicin, prednisone)-BV representing a new treatment paradigm in CD30+ PTCL although its benefit is less certain in the non-anaplastic large cell lymphoma subtypes. Given the high risk of relapse, consolidative autologous stem cell transplant is considered in nodal PTCL, outside of ALK-positive anaplastic large cell lymphoma; however, in the absence of a randomized controlled trials, practices vary. Beyond CHP-BV, most study activity has focused on adding a novel agent to CHOP (i.e., CHOP + drug X). However, with high complete remission rates observed with some novel therapy combinations, these regimens are being tested in the front-line setting, with a particular rationale in follicular helper T-cell lymphomas which have a clear sensitivity to epigenetic modifying therapies. This is well exemplified in the relapsed/refractory setting in which rational combination therapies are being developed for specific subtypes or guided by underlying biology. Taken together, we have finally moved into an era of a more personalized approach to the management of nodal PTCL.

Diffuse large B-cell lymphoma.

Large B-cell lymphoma, the prototype of aggressive non-Hodgkin lymphomas, is both the most common lymphoma and accounts for the highest global burden of lymphoma-related deaths. For nearly 4decades, the goal of treatment has been "cure", first based on CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and subsequently with rituximab plus CHOP. However, there is significant clinical, pathologic, and biologic heterogeneity, and not all patients are cured. Understanding and incorporating this biologic heterogeneity into treatment decisions unfortunately is not yet standard of care. Despite this gap, we now have significant advances in frontline, relapsed, and refractory settings. The POLARIX trial shows, for the first time, improved progression-free survival in a prospective randomized phase 3 setting. In the relapsed and refractory settings, there are now many approved agents/regimens, and several bispecific antibodies poisedto join the arsenal of options. While chimeric antigen receptor T-cell therapy is discussed in detail elsewhere, it has quickly become an excellent option in the second-line setting and beyond. Unfortunately, special populations such as older adults continue to have poor outcomes and be underrepresented in trials, although a new generation of trials aim to address this disparity. This brief review will highlight the key issues and advances that offer improved outcomes to an increasing portion of patients.

Assessment of Frequency and Severity of ADRS Related with CHOP Therapy in Lymphoma Treatment

Background: Lymphoma a blood related cancer usually treated by using combination of various chemotherapeutic agents, one of the common treatments is CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone). Objective: Objective of this study was to identify frequency and severity of ADRs affecting various systems due to CHOP therapy from which patients are suffering, so that proper health strategy can be designed to overcome them. Methodology: study conducted was a prospective, observational enrolled 100 patients suffering from Non-Hodgkin Lymphoma and receiving CHOP combination therapy from November 2015 to April 2018 at Cancer Hospital Jamshoro, sampling technique used was purposive. The response on ADRs was recorded and these were verified by comparing against British National Formulary (2017) ad Lexi Comp Drug Information Handbook (2015). Results: Among 100 patients enrolled aged 18-65 years in which females comprise the majority. The common ADRs reported were nausea 71%, fatigue 69% and alopecia 68% The patients who responded about high severity ADRs also tend to stay longer as compared to those with less severity one. Conclusion: The study results show that patients receiving lymphoma treatment suffers from high severity ADRs require supportive medical care as this lead to prolong effects after dose cycle. These patients must be counselled for supportive medication and food intake to prevent additional health risks to achieve maximum therapeutic benefits. Keywords: Cancer, Anticancer Drugs, Chemotherapy, CHOP Therapy, ADRs

Retrospective Analysis With Propensity Score Matching of Peripheral T-Cell Lymphoma Treated Frontline With Brentuximab Vedotin and Chemotherapy.

Since Food and Drug Administration approval of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (A + CHP) as initial therapy for previously untreated CD30-expressing peripheral T-cell lymphoma (PTCL), there has been limited research on real-world patient characteristics, treatment patterns, and clinical outcomes. We retrospectively analyzed claims of patients with PTCL treated with frontline A + CHP or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) using the Symphony Health Solutions database. Adults with International Classification of Diseases-9/10 PTCL diagnosis codes who initiated A + CHP or CHOP between November 2018 and July 2021 were included. A 1:1 propensity score matching analysis was performed that adjusted for potential confounders between groups. A total of 1344 patients were included (A + CHP, n = 749; CHOP, n = 595). Before matching, 61% were men; median age at index was 62 (A + CHP) and 69 (CHOP) years. The most common A + CHP-treated PTCL subtypes were systemic anaplastic large cell lymphoma (sALCL; 51%), PTCL-not otherwise specified (NOS; 30%), and angioimmunoblastic T-cell lymphoma (AITL; 12%); the most common CHOP-treated subtypes were PTCL-NOS (51%) and AITL (19%). After matching, similar proportions of patients treated with A + CHP and CHOP received granulocyte colony-stimulating factor (89% vs. 86%, P = .3). Fewer patients treated with A + CHP received subsequent therapy than CHOP overall (20% vs. 30%, P < .001) and specifically with the sALCL subtype (15% vs. 28%, P = .025). Characteristics and management of this real-world PTCL population who were older and had a higher comorbidity burden than that in the ECHELON-2 trial demonstrate the importance of retrospective studies when assessing the impact of new regimens on clinical practice.

Estimating long-term progression-free and overall survival in patients with peripheral T-cell lymphoma: A US population-based oncology simulation model based on 5-year results from the ECHELON-2 trial.

BACKGROUND: The ECHELON-2 5-year update showed continued clinically meaningful improvements in progression-free survival (PFS) and overall survival with frontline (1L) A+CHP (brentuximab vedotin in combination with cyclophosphamide, doxorubicin, prednisone) vs CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in CD30-expressing peripheral T-cell lymphomas (PTCLs). OBJECTIVE: To estimate PTCL annual prevalence in the United States in 2031 without and with A+CHP using data from the ECHELON-2 5-year update. METHODS: Population-level outcomes were estimated using a dynamic oncology simulation model. Utilization of 1L CHOP (65% utilization) and CHOP plus etoposide (35% utilization) were varied over time and compared with scenarios incorporating 1L A+CHP (20%-50% utilization; base case: 40% utilization) per expert clinicians' opinion. Additional inputs included PTCL incidence and PFS for consolidation and post-1L therapies from published sources. PFS (51.4% [95% CI = 42.8%-59.4%] vs 43.0% [35.8%-50.0%]) and overall survival (hazard ratio = 0.72 [0.53-0.99]) for A+CHP and CHOP came from ECHELON-2. RESULTS: In 2031, an estimated 2,082 patients will be diagnosed with PTCL. Approximately 1,412 additional patients will be alive and progression free, and 106 fewer patients will require second-line therapy with 40% A+CHP utilization vs no A+CHP utilization. Varying 1L A+CHP utilization from 20%-50% vs no 1L A+CHP utilization added 732 to 1,752 patients alive and progression free. CONCLUSIONS: In this oncology simulation model, the improvements in survival outcomes seen with A+CHP vs CHOP in the ECHELON-2 5-year results translated into more estimated patients with PTCL progression free and alive for at least 5 years following 1L A+CHP vs CHOP and a decreased need for post-1L therapy. DISCLOSURES: This study was funded by Seagen Inc. Dr Liu and Dr Yu are employees and shareholders of Seagen Inc. Mr Bloudek is and Dr Mordi was an employee of Curta Health, which received funding from Seagen Inc. for the conduct of this study. Dr Burke received consulting fees from Genentech/Roche, AbbVie, Seattle Genetics, Bayer, AstraZeneca, Adaptive Biotechnologies, Verastem, MorphoSys, Kura, Epizyme, BeiGene, Kymera, Novartis, Bristol Myers Squibb, TG Therapeutics, Lilly, and Nurix; and received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events in speakers bureaus for BeiGene and Seagen Inc. Dr Phillips received consulting fees from AstraZeneca, MorphoSys, Epizyme, Roche/Genentech, Epizyme Eli Lilly, AbbVie, BeiGene, Pharmacyclics, Bristol Myers Squibb, Xencor, Seagen Inc., TG Therapeutics, Bayer, Incyte, and Gilead; and received payment for honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Epizyme and Seagen Inc.

DELAYED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH) DIAGNOSIS IN A PATIENT WITH PULMONARY SARCOIDOSIS AND NEWLY DIAGNOSED T-CELL LYMPHOMA: A CASE REPORT

DELAYED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH) DIAGNOSIS IN A PATIENT WITH PULMONARY SARCOIDOSIS AND NEWLY DIAGNOSED T-CELL LYMPHOMA: A CASE REPORT

Therapy for patients with POD24 follicular lymphoma: Treatment patterns and outcomes from the Lymphoma Epidemiology of Outcomes (LEO) Consortium.

7573 Background: While most patients (pts) with follicular lymphoma (FL) usually have favorable outcomes, those with refractory disease after first-line anti-CD20 based immunochemotherapy (IC), or progression within 24 months of diagnosis (POD24) have higher risk of premature death. There are no standard approaches for treating this vulnerable group and studies testing novel agents are ongoing in this setting. We sought to investigate clinical practice treatment choices and efficacy for pts with POD24 that align with eligibility criteria for the randomized SWOG1608 which compares IC with novel agents in this population. Methods: This was a multicenter observational cohort study from the LEO Consortium. Eligible pts had grade 1-3a FL diagnosed between 1/1/2002 and 2/1/2019, and initiated therapy after POD24 to first-line bendamustine or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) based IC. Observation, radiotherapy, or rituximab monotherapy were permitted prior to IC and pts with transformation prior to the subsequent therapy after IC were excluded as per S1608. Outcomes of interest were overall and complete response rate (ORR/CR), progression-free survival (PFS), and overall survival (OS). Results: We identified 196 eligible pts with early progression to IC (39% antiCD20 Benda; 61% antiCD20 CHOP) who received subsequent therapy. Median age at post IC treatment was 57 years, 78% grade 1-2 FL. Treatments for pts with POD24 included CHOP- or Benda-based in 31%, salvage/hematopoietic stem cell transplant (HSCT) in 27%, novel therapies in 10% (including phosphatidylinositol 3-kinase inhibitors), antiCD20 monotherapy in 9%, and lenalidomide-based treatment in 8% (table); 21% of pts were treated on clinical trials. Across all treatments, ORR (CR) was 63% (37%) (95% CI: 55-70). At a median follow up of 6.2 years, 2 year PFS was 22% (95% CI: 17%-29%) and 5 year OS was 71% (95% CI: 65-79). Outcomes by regimen are shown in the table. Conclusions: Pts with FL experiencing POD24 following first-line IC are treated heterogeneously, with many pts still receiving IC as subsequent therapy. Despite modest CR rates and low 2-year PFS, 5-year OS appear to be improving compared to historical outcomes. This supports the ongoing need to investigate novel treatments in this population. [Table: see text]

A Retrospective Analysis: Autologous Peripheral Blood Hematopoietic Stem Cell Transplant Combined With Adoptive T-Cell Therapy for the Treatment of High-Grade B-Cell Lymphoma in Ten Dogs.

In humans, a type of cellular immunotherapy, called adoptive T cell transfer (ACT), can elicit curative responses against hematological malignancies and melanoma. ACT using ex vivo expanded peripheral blood T-cells after multiagent chemotherapy enhances tumor-free survival of dogs with B-cell lymphoma (LSA). Since 2008, our group has been performing autologous peripheral blood hematopoietic stem cell transplants (autoPBHSCT) for the treatment of canine high-grade B-cell LSA, although relapse of residual disease is a common cause of reduced survival in ~70% of treated dogs. We reasoned that a more aggressive treatment protocol combining CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, autoPBHSCT, and ACT to treat 10 dogs with B-cell LSA could lead to better outcomes when compared to dogs treated with CHOP chemotherapy and autoPBHSCT alone. Using this protocol, once dogs achieved complete hematologic reconstitution post-autoPBHSCT, CD3+ CD8+ and CD3+CD4+ T-cells were expanded from the peripheral blood at a commercial laboratory. Two to four ACT infusions were given to each dog, with a total of 23 infusions given. Infusions were administered with no complications or adverse events. The median cell dose for all infusions was 5.62 x 106 cells/kg (range: 2.59 x 106-8.55 x 106 cells/kg). 4/10 (40%) of dogs were cured of their disease (defined as disease-free for ≥2 years post-autoPBHSCT). Our results confirm that the autoPBHSCT protocol did not hinder the in vitro expansion of autologous peripheral blood T-cells and that the final product could be administered safely, with no adverse events recorded. Finally, since only ten dogs were treated, our results can only suggest that the administration of ACT to dogs after multiagent chemotherapy and autoPHSCT did not lead to a statistically significant increase in median disease-free interval and overall survival when compared to dogs who received CHOP chemotherapy and autoPHSCT alone.

CHOP Plus Sequential Mogamulizumab As First-Line Therapy for Untreated Adult T-Cell Leukemia-Lymphoma

Introduction: Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. In younger patients, allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to improve prognosis through a graft-versus-ATL (GvATL) effect. On the other hand, elderly patients with ATL are often not amenable to HSCT, and the prognosis is extremely poor with existing chemotherapy. The most widely used chemotherapy for ATL, CHOP (combination of cyclophosphamide-doxorubicin-vincristine-prednisone) and similar chemotherapy, have shown a complete response (CR) rate of about 20% and a long-term prognosis of less than 10%. In a phase II study of mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, in concurrent combination with chemotherapy (mLSG15), the primary endpoint of CR was 52% in the mLSG15 + mogamulizumab group compared to 33% in the mLSG15 alone group. However, no improvement was observed in overall survival (OS) or progression-free survival (PFS). In addition, mLSG15 is a potent chemotherapy and not feasible in majority of elderly patients. Considering the possibility that mogamulizumab may unlock the tumor immune evasion mechanism by removing regulatory T cells and exert an immunological effect like GvATL, we investigated its usefulness as an immunological consolidation therapy following chemotherapy, with the aim of suppressing recurrence.Methods: New-onset treatment-naive ATL patients who were not eligible to HSCT received 3 courses of CHOP (combination of cyclophosphamide div 750 mg/m 2/day1, doxorubicin iv 50 mg/m 2/day1, vincristine iv 1.4 mg/m 2/day1 [max. 2.0 mg/body, and prednisone po/iv 100 mg/body/day1-5) at 21-day intervals, and then the first course of mogamulizumab (1 mg/kg for 8 doses at 2-week intervals) was initiated between the start of the third course of CHOP-21 and day 42. The primary endpoint was OS at months 12. Secondary endpoints were proportion of subjects with PFS, OS, overall response rate (ORR), organ-specific response rate, CR rate and adverse events (AEs) at month 12.Results: A total of 24 patients were enrolled and the median age was 75.5 years (range, 64-85). The median follow-up period was 11.0 (3.0-30.6) months. Five subjects discontinued study treatment before mogamulizumab administration attributable to insufficient effect (n=2), continuation deemed inappropriate (n=2), and start of the next course extended (n=1). ORR was 87.5%. Organ-specific response rates for peripheral blood, other than peripheral blood, target lesion, and skin lesion were 83.3%, 87.5%, 79.2%, and 66.7%, respectively.OS and PFS rates in the full analysis set (FAS) at months 12 were 52.6 (30.9-70.4)% and 26.6 (10.9-45.3)%, respectively. The median survival time (MST) and 80% confidence interval (CI) for OS was 12.1 (5.0 -21 .0) months (Figure 1). Since the lower limit of the 80% CI was below the threshold of 6 months, this treatment was not considered to be effective. However, the point estimate of MST was 12.1 months, which was equivalent to the expected value. One possible reason for the failure to reach statistical significance could be attributable to occurrence of events in the early stage of the protocol regimen. In other words, patients who did not respond to the preceding chemotherapy did not benefit from mogamulizumab, and only patients who managed to overcome chemotherapy benefited from the immune effects of mogamulizumab, resulting in long-term survival (Figure 1). In the long-term follow-up, the MST (95% CI) of the FAS was 12.4 (4.9-21.0) months, and the median OS (95% CI) at 24 months was 25.1 (9.6-44.1) %.AEs were observed in 16 subjects, of which serious AEs (grade 4/5) were observed in 5 subjects (acute respiratory distress syndrome, ventricular fibrillation, heart failure, hyponatremia, and pneumonia). Largely, AEs were resolved/recovered in 14 subjects including 3 subjects with serious AE; 2 subjects resulted in death, which were not considered treatment-related.Conclusions: Mogamulizumab as an immunological consolidation therapy after CHOP 21 might be one of the treatment options for transplant-ineligible elderly patients with previously-untreated ATL, despite not clearly showing improved OS. Further studies are warranted to examine the dosing timing of mogamulizumab to obtain its maximum benefit for prolonged survival. [Display omitted] DisclosuresKato: Abbvie: Consultancy, Research Funding; AstraZeneca: Consultancy; Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Dainippon-Sumitomo: Honoraria; Eisai: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; MSD: Honoraria; Mundi: Honoraria; Novartis: Consultancy, Research Funding; Ono: Honoraria, Research Funding. Suzuki: Kyowa-kirin: Honoraria, Research Funding, Speakers Bureau; Chugai: Honoraria, Research Funding, Speakers Bureau; Taiho: Research Funding; Ohtsuka: Honoraria, Research Funding; Takeda: Research Funding, Speakers Bureau; Shionogi: Research Funding; Eisai: Honoraria, Research Funding; Bristol-Meyer Squib: Honoraria; MSD: Honoraria; Janssen: Honoraria; Abbvie: Speakers Bureau; Meiji Seika: Honoraria, Speakers Bureau; Ohtsuka: Honoraria. Akashi: Sumitomo Dainippon Pharma: Consultancy; Kyowa Kirin: Consultancy, Research Funding; Celgene: Research Funding; Astellas Pharma: Research Funding; Shionogi: Research Funding; Asahi Kasei Pharma: Research Funding; Chugai: Research Funding; Bristol-Myers Squibb: Research Funding.

CAR T Therapy Referral for Diffuse Large B Cell Lymphoma (DLBCL) By U.S. Community Hematology/Oncology (cH/O) Practices: Perceptions and Patterns

IntroductionChimeric antigen receptor T-cell (CAR T) therapy has resulted in a treatment paradigm shift for certain hematologic malignancies, with United States Food and Drug Administration approval of several products for patients with relapsed/refractory (RR) aggressive B cell lymphomas (BCL). Although most BCL patients are initially treated by cH/O physicians, current delivery of CAR T is limited to major academic centers. Consequently, there is a dearth of reporting on the complex aspects of cH/O involvement before and after CAR T therapy administration, which complicates determination of the magnitude of potential benefits. To appropriately incorporate this therapeutic option, and optimize patient care, communication and cooperation between cH/O and the CAR T center is critical; at a minimum, the referring cH/O's access to all aspects of the CAR T therapy continuum is paramount. To that end, this study surveyed cH/O physicians to determine: 1) whether adequate data were recorded and available to the cH/O; 2) timing of referral, leukapheresis, and CAR T infusion; 3) treatment prior to CAR T referral, and 4) physician perceptions on patient eligibility, barriers to access, and noncompliance.MethodsThis retrospective, observational, multicenter chart review assessed adult patients with RR DLBCL who received CAR T therapy in 2019. Patients with ≥6 months of post-CAR T therapy administration follow-up were identified by cH/O physicians participating in the Cardinal Health Oncology Provider Extended Network (OPEN). cH/O physicians provided their perceptions and experience with CAR T therapy via survey and abstracted patient data using electronic case report forms. Patient demographic/clinical/treatment characteristics and physician perceptions were summarized descriptively.ResultsSurveyed Perceptions: Top barriers to CAR T referral: patient choice (39%), location of CAR T center (31%), and preference for other therapy (31%); 39% reported no specific barriers. Rapid disease progression (69%) was the main reason patients would not undergo CAR T therapy after referral, followed by patient ineligibility (62%), patient choice (62%), and insurance coverage/patient cost (46%). Chart Abstraction: Data on 65 RR DLBCL patients were collected from 13 cH/O practices in all 4 U.S. regions (Table). Median duration of follow-up from CAR T therapy referral was 15 months. Median age at RR DLBCL diagnosis was 60 years, and most patients were male (63%) and White (79%). Most patients (92%) received anti-CD20 monoclonal antibody (mAb) + CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as 1L therapy. At referral, 80% of patients (48/60) had lactate dehydrogenase levels above the upper limit of normal. Prior to CAR T infusion, all patients were reported to receive lymphodepletion treatment with fludarabine + cyclophosphamide. Median intervals among patients with and without disease progression, respectively, were: 9 weeks (8 vs 10) from CAR T referral to CAR T infusion, which comprised 5 weeks (4 vs 6) from CAR T referral to leukapheresis and 4 weeks (both groups) from leukapheresis to CAR T infusion.ConclusionsThe cH/O physicians' perceived barriers to CAR T therapy for their patients appear to conflict with the patient data; 69% thought that rapid disease progression precluded CAR T therapy but the reported 9-week interval from referral to CAR T infusion suggests reasonably timely intervention. This highlights the critical need for early referral with a commitment to prompt patient evaluation by the treatment center. The cH/O physician is vital for CAR T referrals and treatment decisions, and the recent increasing access to patients via telemedicine may help better integrate the cH/O, the patient, and the treatment center to promote access of patients to CAR T cell therapies, particularly when limited other options are available. [Display omitted] DisclosuresPorter: DeCart: Membership on an entity's Board of Directors or advisory committees; American Society for Transplantation and Cellular Therapy: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees; ASH: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Genentech: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Tmunity: Patents & Royalties; Wiley and Sons Publishing: Honoraria. Klink: Cardinal Health: Current Employment, Current holder of stock options in a privately-held company. Balanean: Cardinal Health: Current Employment; Georgia State University: Other: former student and employee. McAllister: Cardinal Health: Current Employment. Feinberg: Cardinal Health: Current Employment.

Primary gastric non-Hodgkin lymphomas: Recent advances regarding disease pathogenesis and treatment.

Primary gastric lymphomas (PGLs) are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly. Their main histological types are diffuse large B-cell lymphoma (DLBCL) or mucosa-associated lymphoma tissue. PGL has been one of the main fields of clinical research of our group in recent years. Although gastric DLBCLs are frequent, sufficient data to guide optimal care are scarce. Until today, a multidisciplinary approach has been applied, including chemotherapy, surgery, radiotherapy or a combination of these treatments. In this minireview article, we provide an overview of the clinical manifestations, diagnosis and staging of these diseases, along with their molecular pathogenesis and the most important related clinical published series. We then discuss the scientific gaps, perils and pitfalls that exist regarding the aforementioned studies, in parallel with the unmet need for future research and comment on the proper methodology for such retrospective studies. Aiming to fill this gap, we retrospectively evaluated the trends in clinical presentation, management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in 1980-2014. The study cohort was divided into two subgroups, comparing the main 2 therapeutic options [cyclophosphamide doxorubicin vincristine prednisone (CHOP) vs rituximab-CHOP (R-CHOP)]. A better outcome with immunochemotherapy (R-CHOP) was observed. In the next 2 mo, we will present the update of our study with the same basic conclusion.

Mogamulizumab Monotherapy in the Treatment of Relapsed/Refractory Peripheral T-Cell Lymphoma or Cutaneous T-Cell Lymphoma Patients in Single-Institution Experience

Objectives; T-cell lymphomas generally have a poor outcome with shorter long-term survival compared with B-cell lymphomas. CC chemokine receptor 4 (CCR4) is highly expressed by aggressive peripheral T-cell lymphoma, not otherwise specified (PTCLs), particularly adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphomas (CTCLs). Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody that targets CCR4. In phase II study, Mogamulizumab has been shown to high clinical efficacy and low toxicity. However, its efficacy has not been well evaluated in the clinical setting. We retrospectively analyzed the efficacy and safety of Mogamulizumab of against relapsed/refractory non- ATL T-cell lymphomas.Methods; Fourteen patients with relapsed/ refractory CCR4 positive PTCLs or CTCL were treated with weekly Mogamulizumab (1.0 mg/kg) alone at Iwate Prefectural Central Hospital between January 2015 and June 2017. CCR4 expression was determined by immunohistochemistry by a central laboratory center (SRL, Tokyo, Japan). In the first line, most patients receive commonly anthracycline-containing induction chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). The patients had received a median of one previous chemotherapy regime (range 1-3).We retrospectively evaluated (1) the best overall response, (2) progression-free survival (PFS), (3) overall survival (OS), (4) the best response according to disease site(peripheral blood; PB, lymph nodes; LN and skin) and (5) safety. Response assessments were performed after eighth mogamulizumab infusions according to the 1999 IWG criteria guidelines for response assessments for NHL (IWG-NHL). Treatment efficacy in patients with CTCL was evaluated by using a Global Response Score. Treatment was discontinued if progressive disease (PD) was evident.For safety evaluations, adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs, version 4.0.Results; The median age was 69 years old (range 48-85). Eight patients are male. The diagnosis comprised PTCLs (n=12) and CTCL (n=2). The median follow up periods and median number of Mogamulizumab infusion were 293 days (range 49- 681) and 8 courses (range 2- 9). (1) Complete remission (CR) was achieved in two patients (16.7%) and partial remission in one patients (8.3%), stable disease (SD) in two patients (16.7%), respectively. And (2) median PFS was 88 days and (3) median OS was 475 days. Peripheral blood, lymph node and skin lesion were affected in two, ten, and six patients, respectively. (4) In PB, complete response (CR) was obtained in all two patients (100%) and two patients were achieved CR in skin lesion (33.3%). In LN, only one of ten patient manifested CR(10.0%). This patient's tumor burden is low. (5) With regard to safety issues, hematological AEs were frequently observed, and lymphocytopenia occurred in 62.5% of patients. However, the AEs were controllable and tolerated. Non-hematological AEs, including fever, infusion reactions and skin trouble , were frequently observed (37.5%, 25.0%, and 37.5%, respectively). Grade 3/4 non-hematological AEs were scarcely observed.Conclusions; Although Mogamulizumab monotherapy is effective with highly safety, the patients who had swollen lymph node may need combination chemotherapy with mogamulizumab. The number of patients was small in this retrospective analysis, further investigation are required. DisclosuresNo relevant conflicts of interest to declare.

Adult T cell- leukemia/lymphoma associated with HTLV-1 presenting as giant mass of the face

A 30-year-old Arabic woman of low socio-economic status, without medical history of HIV infection, presented to our department for neglected giant mass of the face evolving for 2 years. She was treated for long time with herbal traditional treatments, which explains the delay of consultation. Physical examination revealed a bulky tumor, of reddish-brown color, occupying the entire face below the franc, more lateralised on the left side. The right eye had restricted movement, while the left eye was fixed (Panel A,B). CT scan showed a nasal cavity tumour with orbital and maxillary sinus invasion, without intra cranial extension or distant metastasis. Laboratory testing was positive for HTLV I/II and she was negative for HIV. Surgical biopsy with histo-pathological study established the diagnosis of HTLV-1 associated adult lymphoma/leukaemia, with strong CD4 and CD25 antibody staining. She received chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen, but she died after two cycles.

Preliminary evaluation of probiotic effects on gastrointestinal signs in dogs with multicentric lymphoma undergoing multi-agent chemotherapy: A randomised, placebo-controlled study.

BackgroundGastrointestinal (GI) toxicity is a major dose‐limiting factor in dogs undergoing chemotherapy. A proposed mechanism of GI toxicity includes chemotherapy‐driven GI dysbiosis. This study was designed to determine the effects of probiotic administration on GI side‐effects in dogs receiving multi‐agent chemotherapy.MethodsTen client‐owned dogs with multicentric lymphoma were enrolled in a prospective, randomised, placebo‐controlled single‐blinded study. On the first day of the cyclophosphamide doxorubicin vincristine prednisone (CHOP)‐based chemotherapy protocol, dogs were randomised to receive either daily oral probiotic at a dose of 200 × 109 cfu/10 kg (n = 5) or daily oral placebo (n = 5). Complete blood count, faecal score (FS), faecal microbiome analysis (qPCR) and adverse events scores were performed at baseline and on the day of each subsequent chemotherapy dose, as well as 3 days after doxorubicin (days 0, 7, 14, 21, 24 and 28).ResultsOverall, 40% of dogs had an abnormal GI microbiome at baseline, specifically decreased faecal C. hiranonis and Fusobacterium abundances. Dogs receiving probiotics had increased faecal Streptococcus (p = 0.02) and E. coli. (p = 0.01). No dogs receiving probiotics experienced diarrhoea (FS ≥ 3.5) compared to four of five receiving placebo. (F 2.895; p = 0.13)ConclusionGI microbiome dysbiosis was common in this group of dogs with multicentric lymphoma. Probiotics were well‐tolerated, with no negative side effects. Further studies are needed to explore broader microbiome and metabolome changes, as well as clinical benefit.

GM-CSF enhanced the effect of CHOP and R-CHOP on inhibiting diffuse large B-cell lymphoma progression via influencing the macrophage polarization

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. However, the underlying mechanisms are still largely unknown.MethodsIn the present study, the combination use of CHOP and R-CHOP with GM-CSF was used to evaluate their effects on the tumor immune microenvironment of DLBCL. CHOP and R-CHOP administration was found to inhibit the growth and metastasis of DLBCL, with a higher efficacy in R-CHOP-challenged DLBCL mice. The anti-tumor effect of CHOP and R-CHOP was further amplified by GM-CSF.ResultsCHOP and R-CHOP therapeutics potentiated the anti-tumor properties of macrophages, as evidenced by the increased M1 macrophage and the decreased M2 macrophage accumulation in DLBCL-bearing mice. In a co-culture system, macrophages primed with CHOP and R-CHOP therapeutics inhibited multiple malignant behaviors of DLCBL cells. Mechanistically, CHOP/R-CHOP suppressed the activation of AKT signaling. These anti-tumor effects of CHOP/R-CHOP were all augmented by GM-CSF.ConclusionsOur work provided new insights into the immune-regulatory roles of CHOP and R-CHOP in the treatment of DLBCL, as well as the synergistic effects of GM-CSF in CHOP and R-CHOP therapeutics. Although our results suggest the synergistic effect of GM-CSF on DLBCL already sensitive to CHOP and R-CHOP, however, future studies are warranted to explore the role of GM-CSF on R-CHOP-resistant DLBCL.Trial registration Not applicable.

Exploring the burden of short-term CHOP chemotherapy adverse events in post-transplant lymphoproliferative disease: a comprehensive literature review in lymphoma patients

Purpose Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) is a treatment for post-transplant lymphoproliferative disease (PTLD) following solid organ transplant (SOT) after failing rituximab, an aggressive and potentially fatal lymphoma. This study explores the humanistic and economic burden of CHOP-associated adverse events (AEs) in PTLD patients. Since PTLD is rare, searches included lymphoproliferative disease with lymphoma patients. Design This comprehensive literature review used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol, pre-specifying the search strategy and criteria. CHOP-associated short-term AEs with an incidence of >4% were sourced from published literature and cancer websites to inform the search strategy. PubMed and EMBASE searches were used to identify humanistic and economic burden studies. Results PubMed and EMBASE searches identified 3946 citations with 27 lymphoma studies included. Studies were methodologically heterogeneous. Febrile neutropenia (FN) was the AE most encountered, followed by chemotherapy-induced (CI) anemia (A), infection, CI-nausea and vomiting, thrombocytopenia, and CI-peripheral neuropathy (PN). FN and infections were associated with significant disutility, increased hospitalization, and extended length of stay (LOS). Infections and CIPN significantly impacted the utility of patients and CIA-related fatigue showed reductions in quality of life (QoL). Many patients continue to have QoL deficits continued even after AEs were treated. Management costs varied greatly, ranging from nominal (CIPN) to over $100,000 in the USA for infections, EUR 10,290 in Europe for infections, or CAN$1012 in Canada for FN. Cost of outpatient care varied but had a lower economic impact compared to hospitalizations. Conclusions Short-term AEs from CHOP in the lymphoma population were associated with substantial humanistic and economic burden.

Automated Baseline Fluorodeoxyglucose-Positron Emission Tomography Imaging and High BCL2 Expression Provide Orthogonal Prognostic Value in Predicting High-Risk De Novo Diffuse Large B-Cell Lymphoma Patients

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for 30─40% of cases (Li, et al. Pathology 2017). Although rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) cures approximately 50─60% of patients, clinical outcomes remain poor for those with relapsed or refractory (R/R) disease (Liu and Barta. Am J Hematol 2019). Current prognostic models such as the International Prognostic Index (IPI) have suboptimal sensitivity and specificity to identify these patients at diagnosis. Models that combine biological, clinical and imaging markers may improve prognostication in DLBCL. Methods: We evaluated fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging features alongside clinical and biomarker data in modeling disease prognosis with a primary endpoint of investigator-assessed progression-free survival (PFS) for de novo DLBCL patients from the randomized phase III GOYA study (NCT01287741) comparing R-CHOP versus obinutuzumab (G)-CHOP. Imaging features were derived using a computer-vision modeling algorithm (Jemaa, et al. J Digit Imaging 2020), and included total and by-organ number and volume of lesions. The evaluable population (n=1286) was split into pre-defined training (n=964; PFS events=307) and holdout populations (n=322; PFS events=96). Baseline clinical and imaging features were dichotomized by median or a clinically relevant threshold, and screened with univariate Cox proportional hazard (PH) models (Figure A). Screened variables were further selected to construct a multivariate Cox PH model for risk prognosis utilizing a regularized LASSO Cox regression (Simon, et al. J Statistical Software 2011). Model performance was evaluated by area under the receiver operating characteristic curve (AUC) and C-index on the holdout population. Additional biomarker features were evaluated, including, BCL2 protein expression as determined by Ventana investigational-use only immunohistochemistry (IHC) assay, gene expression quantified by TruSeq® (Illumina) RNAseq, next generation sequencing-based genomic profiling using the FoundationOne HemeTM platform (F1H, Foundation Medicine Inc. [FMI]) and cell of origin (COO) by the Nanostring assay. Results: Total metabolic tumor volume (TMTV), total number of lesions, longest diameter of any lesion, number of kidney lesions, and number of liver lesions were selected as prognostic imaging factors for PFS in de novo DLBCL patients. Strong correlation was observed between corresponding volume and lesion number features, as expected, though collinearity appeared to otherwise be minimal (Figure B). Performance of the resulting model composed of these imaging variables alongside standard clinical features and treatment (AUC=0.66; C-Index=0.64) improved upon a model composed of IPI categories (AUC=0.60; C-Index=0.60). High risk, defined by log-hazard &amp;gt;0 was associated with reduced PFS (Figure C). High BCL2 expression by IHC (score &amp;gt;1) was prognostic for PFS independent of clinical and imaging features (HR, 2.02; CI: 1.36─2.98). High BCL2 was predictive of PFS in patients treated with G-CHOP over R-CHOP in de novo DLBCL patients (HR, 0.55; CI: 0.32─0.97) (Figure D). This trend held when adjusting for COO separate to imaging features. Mutational analysis using the FMI panel also indicated the additional prognostic value of BCL2 and TP53 single-nucleotide variants through selection by LASSO. Conclusions: Automated baseline imaging features and high BCL2 expression demonstrated prognostic value orthogonal to standard clinical features in predicting high-risk de novo DLBCL despite limitations imposed by sample size and multicollinearity among features. These findings support the integration of imaging, genomic and clinical factors in prognostic models to improve the identification of high-risk de novo DLBCL patients. Disclosures Jemaa: F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Tracy:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Bottos:F. Hoffmann-La Roche: Current Employment, Current equity holder in private company. de Crespigny:Genentech, Inc.: Current Employment; F Hoffmann-La Roche: Current equity holder in publicly-traded company. Bengtsson:Genentech, Inc.: Current Employment; F Hoffmann-La Roche: Current equity holder in publicly-traded company. Nielsen:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Paulson:Genentech, Inc.: Current Employment; F. Hoffmann-Roche: Current equity holder in private company, Current equity holder in publicly-traded company.

3D echocardiography, arterial stiffness, and biomarkers in early diagnosis and prediction of CHOP-induced cardiotoxicity in non-Hodgkin\u2019s lymphoma

CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) represents standard chemotherapy in non-Hodgkin's lymphoma (NHL) with risk of cardiotoxicity. To define new parameters, such as 3D myocardial deformation, arterial stiffness, and biomarkers for early diagnosis and prediction of cardiotoxicity. 110 NHL patients with LVEF > 50%, scheduled for CHOP, were evaluated at baseline, after third cycle and chemotherapy completion. 3DE assessed LVEF and myocardial deformation: longitudinal (LS), radial, circumferential, area strain. Echo-tracking analysed arterial stiffness: PWV, β index, wave intensity. Troponin I and NT-pro-BNP were measured. After chemotherapy completion, 18 patients (16%) (group I) developed cardiotoxicity (LVEF decrease < 50%, with > 10% from baseline); 92 patients (group II) did not. Significant reduction of 3D LV deformation and increase of arterial stiffness developed starting with third cycle, with greater changes in group I. LS reduction and PWV increase after third cycle were the best independent predictors for LVEF decrease; the association of LS decrease by > 19% and PWV increase by > 27% after third cycle predicted cardiotoxicity after chemotherapy completion (90% sensitivity and 81% specificity). 3D LS and PWV can detect early chemotherapy-induced cardiotoxicity and predict LVEF decline. These parameters should be incorporated in clinical protocols to monitor cardiovascular function during chemotherapy and early intervention.