Publications by authors named "Christopher R Flowers"

298 Publications

Validation of POD24 As a Robust Early Clinical Endpoint of Poor Survival in FL from 5,225 Patients on 13 Clinical Trials.

Blood 2021 Oct 6. Epub 2021 Oct 6.

University of Texas MD Anderson Cancer Center, Houston, Texas, United States.

Observational studies and standalone trials indicate that patients with follicular lymphoma (FL) who experience disease progression within 24 months of front-line chemoimmunotherapy (POD24), have poor outcomes. We performed a pooled analysis of 13 randomized clinical trials of FL patients in the pre- and post-rituximab era to identify clinical factors predicting POD24. Logistic regression models evaluated the association between clinical factors and POD24. Cox regression evaluated the association between POD24 as a time-dependent factor and subsequent overall survival (OS). A landmark analysis evaluated the association of POD24 on OS for the subset of patients who were alive at 24 months post trial registration. Patients without progression at 24 months at baseline had favorable performance status (PS), limited stage (I/II) disease, low FLIPI risk score, normal baseline hemoglobin, and normal baseline beta 2 microglobulin (B2M). In a multivariable logistic regression model, male gender (odds ratio (OR) = 1.30), PS >= 2 (OR = 1.63), B2M (>= 3mg/L) (OR = 1.43), and high FLIPI risk score (3 - 5) (OR = 3.14) were associated with increased risk of progression before 24 months. In the time-dependent Cox model and the 24 month landmark analysis, POD24 was associated with poor subsequent OS (hazard ratio (HR) = 4.85 and HR = 3.06, respectively). This is the largest pooled analysis using clinical trials data validating POD24 as a robust indicator of poor FL survival and identified clinical predictors of early death and progression that can aid in building comprehensive prognostic models incorporating clinical and molecular predictors of POD24.
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http://dx.doi.org/10.1182/blood.2020010263DOI Listing
October 2021

Early Relapse Identifies MCL patients with Inferior Survival after Intensive or Less Intensive Frontline Therapy.

Blood Adv 2021 Sep 13. Epub 2021 Sep 13.

Medical College of Wisconsin, Milwaukee, Wisconsin, United States.

While an expanding array of effective treatments has resulted in recent improvement in survival for patients with mantle cell lymphoma (MCL), outcomes remain heterogeneous and identification of prognostic factors remains a priority. We assessed the prognostic impact of time to progression of disease (POD) after first-line therapy among 455 patients with relapsed MCL. Patients were categorized by duration of first remission as PRF/POD6, defined as progressive disease during induction or POD within six months of diagnosis (n=65, 14%), POD6-24, defined as POD between six and 24 months from diagnosis (n=153, 34%), and POD>24 defined as POD beyond 24 months from diagnosis (n=237, 53%). Median overall survival from POD (OS2) was 1.3 [95% CI 0.9-2.4] years for PRF/POD6 patients, 3 [95% CI 2-6.8] years for POD6-24, and 8 [95% CI 6.2-NR] years among POD>24 patients. Median OS2 was inferior in patients with early POD (defined as PRF/POD6 or POD6-24) following both intensive and less intensive frontline treatment. The prognostic performance of time to POD was replicated in an independent cohort of 245 patients with relapsed MCL, with median OS2 of 0.3 [95% CI 0.1-0.5] years for PRF/POD6, 0.8 [95% CI 0.6-0.9] years for POD6-24, and 2.4 [95% CI 2.1-2.7] years for POD>24. Early POD is associated with inferior OS2 in patients with relapsed MCL, identifying a high-risk population for future prospective studies.
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http://dx.doi.org/10.1182/bloodadvances.2021004765DOI Listing
September 2021

A prospective study on early PET/CT scans during the first cycle of salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.

Leuk Lymphoma 2021 Aug 26:1-10. Epub 2021 Aug 26.

Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 ( = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments.
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http://dx.doi.org/10.1080/10428194.2021.1971223DOI Listing
August 2021

Multi-center analysis of practice patterns and outcomes of younger and older patients with mantle cell lymphoma in the rituximab era.

Am J Hematol 2021 Nov 10;96(11):1374-1384. Epub 2021 Aug 10.

Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.

Clinical outcomes and predictors of survival in patients with newly diagnosed mantle cell lymphoma (MCL) treated in the rituximab era (2000-2015) at 12 US academic centers were assessed to identify determinants of survival across age groups. Objectives were to characterize and compare practice patterns, outcomes and prognostic factors for survival in younger patients (age < 65) and older patients (age ≥ 65 years). Among 1162 patients included, 697 were younger and 465 were older. In younger patients, 2-year progression free survival (PFS) and overall survival (OS) rates were 79% and 92% respectively; blastoid histology, ECOG ≥ 2, and lack of maintenance rituximab (MR) remained statistically relevant to poor OS on univariate analysis (UVA) and multivariate analysis (MVA). In older patients, 2-year PFS and OS rates were 67% and 86% respectively; lack of maintenance rituximab remained significantly associated with inferior PFS and OS on UVA and MVA (p < 0.001). Two-year PFS rates were 79%, and 67% and 2-year OS rates were 92% and 86% for ages < 65 and ≥ 65 respectively (p < 0.001). First-line high-dose cytarabine exposure and/or MR lessened the negative impact of age on survival. Taken collectively, survival outcomes for older patients remain inferior to those of younger patients in the rituximab era. However, maintenance rituximab and potentially high-dose cytarabine-based induction can mitigate the negative impact of age on survival.
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http://dx.doi.org/10.1002/ajh.26306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511300PMC
November 2021

Influenza Vaccination Rates Among Patients With a History of Cancer: Analysis of the National Health Interview Survey.

Open Forum Infect Dis 2021 Jul 20;8(7):ofab198. Epub 2021 Apr 20.

Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

Background: Annual influenza vaccination is recommended for all patients with cancer, but vaccine uptake data by cancer type and time since diagnosis are limited. We sought to estimate vaccination rates across different cancer types in the United States and determine whether rates vary over time since diagnosis.

Methods: Vaccination rates in individuals with solid tumor and hematological malignancies were estimated using data from 59 917 individuals obtained by the 2016 and 2017 National Health Interview Survey conducted by the Centers for Disease Control and Prevention.

Results: An average of 64% of the 5053 individuals with self-reported cancer received the influenza vaccine. Vaccination rates in men and women with solid tumors (66.6% and 60.3%, respectively) and hematological malignancies (58.1% and 59.2%, respectively) were significantly higher compared to those without cancer (38.9% and 46.8%, respectively). Lower rates were seen in uninsured patients, those younger than 45 years of age, and in African Americans with hematological malignancies but not with solid tumors. Vaccine uptake was similar regardless of time since cancer diagnosis.

Conclusions: Influenza vaccination rates are higher in men and women with cancer but remain suboptimal, highlighting the need for additional measures to improve vaccine compliance and prevent complications from influenza across all cancer types.
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http://dx.doi.org/10.1093/ofid/ofab198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312520PMC
July 2021

CRP and ferritin in addition to the EASIX score predict CAR-T-related toxicity.

Blood Adv 2021 07;5(14):2799-2806

Department of Stem Cell Transplantation and Cellular Therapy.

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.
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http://dx.doi.org/10.1182/bloodadvances.2021004575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341350PMC
July 2021

Acalabrutinib for treatment of diffuse large B-cell lymphoma: results from a phase Ib study.

Haematologica 2021 Oct 1;106(10):2774-2778. Epub 2021 Oct 1.

Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester.

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http://dx.doi.org/10.3324/haematol.2021.278654DOI Listing
October 2021

Surveillance imaging during first remission in follicular lymphoma does not impact overall survival.

Cancer 2021 Sep 22;127(18):3390-3402. Epub 2021 Jun 22.

Department of Hematology and Medical Oncology, Emory University-Winship Cancer Institute, Atlanta, Georgia.

Background: Although many patients with follicular lymphoma (FL) undergo routine radiographic surveillance during their first remission, no consensus exists on the modality, duration, frequency, or need for routine imaging studies. The authors retrospectively examined the effect of surveillance imaging on relapse detection and overall survival (OS) in patients with FL.

Methods: Patients with newly diagnosed FL who had a response to induction therapy were identified from the Lymphoid Malignancies Enterprise Architecture Database (LEAD) at Emory University and from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic. Patients were evaluated for both relapse and method of relapse detection (ie, clinical concerns vs radiologic detection through surveillance imaging in an asymptomatic patient).

Results: Of 148 patients in the LEAD cohort, 55 (37%) relapsed, and the majority (n = 35; 64%) of relapses were detected clinically. In the MER cohort, 63 of 177 relapses (54%) were detected clinically. There was no significant difference in OS from the date of diagnosis between the 2 methods of relapse detection in the LEAD (hazard ratio [HR], 0.61; 95% CI, 0.13-2.94; P = .54) and MER (HR, 1.02; 95% CI, 0.47-2.21; P = .96) cohorts. Similarly, there was no significant difference in OS from the date of relapse between the 2 methods of relapse detection in the LEAD (HR, 0.47; 95% CI, 0.10-2.27; P = .35) and MER (HR, 1.02; 95% CI, 0.47-2.21; P = .96) cohorts.

Conclusions: These findings suggest a limited role for routine surveillance imaging in patients with FL who complete front-line therapy. Future studies should evaluate which patients may benefit from a more aggressive surveillance approach and should explore novel methods of relapse detection.
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http://dx.doi.org/10.1002/cncr.33660DOI Listing
September 2021

Body mass index and survival of patients with lymphoma.

Leuk Lymphoma 2021 Jun 14:1-8. Epub 2021 Jun 14.

Department of Health and Human Services, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

The impact of body mass index (BMI) on survival in lymphoma remains controversial. We leveraged a prospective cohort of lymphoma patients enrolled to SPORE Molecular Epidemiology Resource between 2002 and 2015 to assess the association of BMI before diagnosis, BMI at diagnosis, and BMI change over time with lymphoma-specific survival (LSS). A total of 4009 lymphoma patients (670 diffuse large B-cell lymphoma (DLBCL), 689 follicular lymphoma (FL), 1018 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and 1632 other subtypes) were included. Significantly shorter LSS after diagnosis was observed for FL patients who were obese before diagnosis (HR: 3.02, 95%CI: 1.43-6.41, =.004) and for those with  ≥ 5% increase in BMI from diagnosis to 3-year follow-up (HR: 3.53, 95%CI: 1.22-10.2, =.020). In contrast, obesity prior to or at the time of diagnosis was not associated with LSS in DLBCL and CLL/SLL. The impact of weight control after diagnosis in FL patient warrants investigation.
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http://dx.doi.org/10.1080/10428194.2021.1929956DOI Listing
June 2021

Intensive induction regimens after deferring initial therapy for mantle cell lymphoma are not associated with improved survival.

Eur J Haematol 2021 Sep 17;107(3):301-310. Epub 2021 Jun 17.

Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, US.

Introduction: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy.

Methods: Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Patients who received induction with high-dose cytarabine and/or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy (n = 88) while all other approaches were non-intensive (n = 131).

Results: There was no difference in progression-free (PFS; P = .224) or overall survival (OS; P = .167) in deferred patients who received non-intensive vs. intensive therapy. Additionally, univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Treatment at an academic center (HR 0.43, P = .015) was associated with improved OS in both univariate and multivariate models, while intensity of treatment was not associated with improved OS in either model.

Conclusions: These results indicate that intensified initial treatment is not associated with improved survival after deferring initial therapy, although prospective studies are needed to determine which of these patients with MCL may benefit from intensive therapy.
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http://dx.doi.org/10.1111/ejh.13649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338766PMC
September 2021

The bidirectional increased risk of B-cell lymphoma and T-cell lymphoma.

Blood 2021 Sep;138(9):785-789

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Lymphoma survivors have a significantly higher risk of developing second primary lymphoma than the general population; however, bidirectional risks of developing B- and T-cell lymphomas (BCLs and TCLs) specifically are less well understood. We used population-based cancer registry data to estimate the subtype-specific risks of second primary lymphoma among patients with first BCL (n = 288 478) or TCL (n = 23 747). We observed nearly fivefold increased bidirectional risk between BCL and TCL overall (TCL following BCL: standardized incidence ratio [SIR] = 4.7, 95% confidence interval [CI] = 4.2-5.2; BCL following TCL: SIR = 4.7, 95% CI = 4.1-5.2), but the risk varied substantially by lymphoma subtype. The highest SIRs were observed between Hodgkin lymphoma (HL) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) (PTCL-NOS following HL: SIR = 27.5; HL following PTCL-NOS: SIR = 31.6). Strikingly elevated risks also were notable for angioimmunoblastic T-cell lymphoma (AITL) and diffuse large B-cell lymphoma (DLBCL) (AITL following DLBCL: SIR = 9.7; DLBCL following AITL: SIR = 15.3). These increased risks were strongest within the first year following diagnosis but remained persistently elevated even at ≥5 years. In contrast, SIRs were <5 for all associations of TCL with chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. These patterns support etiologic heterogeneity among lymphoma subtypes and provide further insights into lymphomagenesis.
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http://dx.doi.org/10.1182/blood.2020010497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414260PMC
September 2021

Understanding and Addressing Disparities in Patients With Hematologic Malignancies: Approaches for Clinicians.

Am Soc Clin Oncol Educ Book 2021 Mar;41:1-7

Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer, Houston, TX.

Approximately 185,840 individuals will be diagnosed with hematologic malignancies in the United States in 2020. Disparities in disease incidence, prevalence, burden, mortality, and survivorship have been identified among this patient population. Contributing factors include genetic ancestry, race/ethnicity, sex, socioeconomic status, and geographic region. Historically, these inequities have been understudied. Addressing these disparities requires a systems-level approach, improving access to care and reducing biases in the clinical setting. Additional research is needed to construct comprehensive, multilevel models to explore systematic observational studies and perform strategic intervention trials to overcome these disparities.
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http://dx.doi.org/10.1200/EDBK_320079DOI Listing
March 2021

Primary Mediastinal B Cell Lymphoma in the Positron-Emission Tomography Era Executive Summary of the American Radium Society Appropriate Use Criteria.

Int J Radiat Oncol Biol Phys 2021 09 24;111(1):36-44. Epub 2021 Mar 24.

Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York.

Purpose: Primary mediastinal B cell lymphoma (PMBCL) is a highly curable subtype of non-Hodgkin lymphoma that is diagnosed predominantly in adolescents and young adults. Consequently, long-term treatment-related morbidity is critical to consider when devising treatment strategies that include different chemoimmunotherapy strategies with or without radiation therapy. Furthermore, adaptive approaches using the end-of-chemotherapy (EOC) positron emission tomography (PET)/computed tomography (CT) scanning may help to determine which patients may benefit from additional therapies. We aimed to develop evidence-based guidelines for treating these patients.

Methods And Materials: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the PubMed database. The ARS expert committee, composed of radiation oncologists, hematologists, and pediatric oncologists, developed consensus guidelines using the modified Delphi framework.

Results: Nine studies met the full criteria for inclusion based on reporting outcomes on patients with primary mediastinal B cell lymphoma with EOC PET/CT response scored with the 5-point Deauville scale. These studies formed the evidence for these guidelines in managing patients with PMBCL according to the EOC PET response, including after a 5-point Deauville scale of 1 to 3, 4, or 5, and for patients with relapsed and refractory disease. The expert group also developed guidance on radiation simulation, treatment planning, and plan evaluation based on expert opinion.

Conclusions: Various treatment approaches exist in the management of PMBCL, including different chemoimmunotherapy regimens, the use of consolidative radiation therapy, and adaptive approaches based on EOC PET/CT response. These guidelines can be used by practitioners to provide appropriate treatment according to different disease scenarios.
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http://dx.doi.org/10.1016/j.ijrobp.2021.03.035DOI Listing
September 2021

Outcomes of older patients with follicular lymphoma using individual data from 5922 patients in 18 randomized controlled trials.

Blood Adv 2021 03;5(6):1737-1745

University of Texas MD Anderson Cancer Center, Houston, TX.

Limited data exist to describe the clinical features and outcomes for elderly patients with follicular lymphoma (FL). The Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) group performed a prospectively planned pooled analysis of individual patient data from first-line randomized controlled trials (RCTs) and examined associations between age (≤70 vs >70 years), clinical characteristics, and FL outcomes. We identified 18 multicenter clinical RCTs in the FLASH database that enrolled elderly patients (>70 years). Primary end points were early disease outcomes, CR24 and CR30, and progression-free survival (PFS) at 24 months (PFS24). Secondary end points were PFS and overall survival (OS). We identified 5922 previously untreated FL patients from 18 RCTs. Patients age >70 years (vs ≤70 years) more commonly had elevated lactate dehydrogenase, hemoglobin <12 g/dL, ECOG PS ≥2, and elevated β2-microglobulin. Median follow-up was 5.6 years. Patients >70 years did not differ from patients ≤70 years in rates of CR24, CR30, or PFS24. With a median OS of 14.6 years for all patients, median OS was 7.4 and 15.7 years for patients >70 and ≤70 years of age, respectively (hazard ratio = 2.35; 95% confidence interval = 2.03-2.73; P < .001). Age >70 years was a significant predictor of OS and PFS due to higher rates of death without progression, but not PFS24, CR24, or CR30. FL patients >70 years treated on trials have similar early disease outcomes to younger patients. There is no disease-specific outcome difference between age groups. Age alone should not disqualify patients from standard treatments or RCTs.
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http://dx.doi.org/10.1182/bloodadvances.2020002724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993094PMC
March 2021

Perceptions of clinical care and research among African-American patients with lymphoma.

Leuk Lymphoma 2021 08 28;62(8):1860-1868. Epub 2021 Feb 28.

Winship Cancer Institute, Emory University, Atlanta, GE, USA.

Across lymphoma subtypes, African Americans experience disparities in clinical trial enrollment and outcomes. Understanding the needs of this population can aid addressing these disparities. Semi-structured interviews were conducted with 14 self-identified Black/African-American lymphoma patients to determine their perceptions and attitudes about aspects of treatment and research. Constant-comparative methods identified themes including trust in medical staff, lack of diagnosis information, interest in research, research priorities, and potentially unaddressed emotional needs. Patients trusted their doctors and desired more diagnosis information. Participants often did not consider the emotions surrounding their diagnoses and concentrated on positive attitudes during treatment. Most participants were interested in clinical trials to help future lymphoma patients. Participants suggested a range of future research topics emphasizing lymphoma etiology. Building on trusting doctor-patient relationships, expanding clinical trials information, addressing emotional needs, and aligning research objectives with patient concerns are potential strategies for increasing clinical trial enrollment among Black lymphoma patients.
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http://dx.doi.org/10.1080/10428194.2021.1892092DOI Listing
August 2021

Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma.

Blood 2021 Jun;137(23):3272-3276

Department of Lymphoma and Myeloma.

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy-associated toxicities.
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http://dx.doi.org/10.1182/blood.2020008865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351896PMC
June 2021

The impact of cell-of-origin, MYC/Bcl-2 dual expression and rearrangement on disease relapse among early stage diffuse large B-cell lymphoma patients treated with combined modality therapy.

Leuk Lymphoma 2021 06 22;62(6):1361-1369. Epub 2021 Jan 22.

Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 - 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with translocations without or rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure.
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http://dx.doi.org/10.1080/10428194.2020.1869965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262455PMC
June 2021

Outcomes of patients with up to 6 years of follow-up from a phase 2 study of idelalisib for relapsed indolent lymphomas.

Leuk Lymphoma 2021 05 10;62(5):1077-1087. Epub 2020 Dec 10.

University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

The phase 2 study of idelalisib monotherapy for indolent non-Hodgkin lymphomas (iNHLs) was completed in 2018; final efficacy and safety data with up to 6.7 years long-term follow-up are reported. Patients with iNHL refractory to both rituximab and an alkylating agent were enrolled and received 150 mg idelalisib twice daily ( = 125). Idelalisib resulted in an overall response rate of 57.6% with 34.4% continuing therapy for ≥12 months. The median progression-free survival and duration of response were 11.0 and 11.8 months for follicular lymphoma, 22.2 and 20.4 months for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM), and 6.6 and 18.4 months for marginal zone lymphoma (MZL). Median overall survival after extended follow-up was 48.6 (95% CI 33.9, 71.7) months. Long-term follow-up did not reveal new safety concerns. These data indicate beneficial outcomes with longer follow-up after idelalisib for treatment of iNHL including in patients with LPL/WM and MZL.
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http://dx.doi.org/10.1080/10428194.2020.1855344DOI Listing
May 2021

Nodular lymphocyte predominant Hodgkin lymphoma: executive summary of the American radium society appropriate use criteria.

Leuk Lymphoma 2021 05 4;62(5):1057-1065. Epub 2020 Dec 4.

University of Rochester Medical Center, Rochester, NY, USA.

This guideline for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by the American Radium Society was developed by a multidisciplinary expert panel of medical, pediatric, and radiation oncologists convened to formulate guidelines for evaluation and treatment. The guideline development was based on an in-depth literature review and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of the recommendations by the panel. Given the scarcity of compelling data for strong recommendations for a rare lymphoma that has been shown to be more indolent than classical Hodgkin lymphoma, in instances where evidence is not available or equivocal, expert opinion guided the recommendations. Four clinical variants exemplify common scenarios and represent the consensus recommendations for patients with nodular lymphocyte Hodgkin lymphoma. A summary of the available published literature is also presented.
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http://dx.doi.org/10.1080/10428194.2020.1852559DOI Listing
May 2021

Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis.

Blood Adv 2020 11;4(22):5773-5784

City of Hope National Medical Center, Duarte, CA.

Advanced marginal zone lymphoma (MZL) is an incurable B-cell malignancy dependent on B-cell receptor signaling. The phase 2 PCYC-1121 study demonstrated the safety and efficacy of single-agent ibrutinib 560 mg/d in 63 patients with relapsed/refractory MZL treated with prior rituximab (RTX) or rituximab-based chemoimmunotherapy (RTX-CIT). We report the final analysis of PCYC-1121 with median follow-up of 33.1 months (range: 1.4-44.6). Overall response rate (ORR) was 58%; median duration of response (DOR) was 27.6 months (95% confidence interval [CI]: 12.1 to not estimable [NE]); median progression-free survival (PFS) was 15.7 months (95% CI: 12.2-30.4); and median overall survival (OS) was not reached (95% CI: NE to NE). Patients with prior RTX treatment had better outcomes (ORR: 81%; median DOR: not reached [95% CI: 12.2 to NE]; median PFS: 30.4 months [95% CI: 22.1 to NE]; median OS: not reached [95% CI: 30.3 to NE]) vs those with prior RTX-CIT treatment (ORR: 51%; DOR: 12.4 months [95% CI: 2.8 to NE]; PFS: 13.8 months [95% CI: 8.3-22.5]; OS: not reached [95% CI: NE to NE]). ORRs were 63%, 47%, and 62% for extranodal, nodal, and splenic subtypes, respectively. With up to 45 months of ibrutinib treatment, the safety profile remained consistent with prior reports. The most common grade ≥3 event was anemia (16%). Exploratory biomarker analysis showed NF-κB pathway gene mutations correlated with outcomes. Final analysis of PCYC-1121 demonstrated long-term safety and efficacy of ibrutinib in patients with relapsed/refractory MZL, regardless of prior treatment or MZL subtype. This trial was registered at www.clinicaltrials.gov as #NCT01980628.
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http://dx.doi.org/10.1182/bloodadvances.2020003121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686907PMC
November 2020

Supporting Decision-Making on Fertility Preservation Among Adolescent and Young Adult Women With Cancer.

Oncology (Williston Park) 2020 11;34(11):494-499

Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia.

Adolescents and young adults (AYAs) with cancer constitute approximately 70,000 patients diagnosed each year. Survival rates for AYAs with cancer have increased steadily in recent decades due to improvements in therapeutic regimens and early detection. Given the large and growing number of AYA cancer survivors, additional research is needed on the immediate and long-term psychosocial support required for this population including family planning and fertility. Fertility and fertility preservation in female AYAs, in particular, is historically understudied and has psychologically relevant ramifications distinct from male AYAs. Decision science can contribute to this area of oncological care and has implications for clinical encounters and research concerning female AYA patients with cancer. Patient-centered care and shared decision-making that integrates recent research regarding fertility preservation in the context of cancer.
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http://dx.doi.org/10.46883/ONC.2020.3411.0494DOI Listing
November 2020

How should clinicians interpret conflicting cost-effectiveness analyses for the treatment of lymphoma across nations and payer models?

Leuk Lymphoma 2020 12 4;61(14):3283-3286. Epub 2020 Nov 4.

Department Chair, Department of Lymphoma/Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA.

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http://dx.doi.org/10.1080/10428194.2020.1837798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959248PMC
December 2020

Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society.

CA Cancer J Clin 2020 09 30;70(5):321-346. Epub 2020 Jul 30.

Prevention and Early Detection Department, American Cancer Society, Atlanta, Georgia.

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.
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http://dx.doi.org/10.3322/caac.21628DOI Listing
September 2020

Linking Environmental Exposures to Molecular Pathogenesis in Non-Hodgkin Lymphoma Subtypes.

Cancer Epidemiol Biomarkers Prev 2020 10 29;29(10):1844-1855. Epub 2020 Jul 29.

Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.

Non-Hodgkin lymphoma comprises a heterogeneous group of hematologic malignancies, with about 60 subtypes that arise via various pathogenetic mechanisms. Although establishing etiology for specific NHL subtypes has been historically difficult given their relative rarity, environmental exposures have been repeatedly implicated as risk factors across many subtypes. Large-scale epidemiologic investigations have pinpointed chemical exposures in particular, but causality has not been established, and the exact biologic mechanisms underpinning these associations are unclear. Here we review chemical exposures that have been associated with development of NHL subtypes and discuss their biologic plausibility based on current research.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541593PMC
October 2020

Maintenance Therapy for Cutaneous T-cell Lymphoma After Total Skin Electron Irradiation: Evidence for Improved Overall Survival With Ultraviolet Therapy.

Clin Lymphoma Myeloma Leuk 2020 11 30;20(11):757-767.e3. Epub 2020 Jun 30.

Winship Cancer Institute of Emory University, Atlanta, GA. Electronic address:

Background: Treatment of cutaneous T-cell lymphoma (CTCL) with total skin electron beam (TSEB) therapy has been associated with deep responses but short progression-free intervals. Maintenance therapy might prolong the response duration; however, limited data assessing the outcomes with maintenance therapy after TSEB are available. We evaluated the effect of maintenance therapy on the outcomes for patients with CTCL receiving TSEB therapy.

Materials And Methods: We conducted a single-center retrospective analysis of 101 patients with CTCL who had received TSEB therapy from 1998 to 2018 at the Winship Cancer Institute of Emory University and compared the overall survival (OS) and progression-free survival (PFS) for patients had received maintenance therapy, including retinoids, interferon, ultraviolet therapy, nitrogen mustard, and extracorporeal photopheresis compared with those who had not.

Results: We found that pooled maintenance therapies improved PFS (hazard ratio [HR], 0.60; P = .026) but not OS (median HR, 0.73; P = .264). The median PFS and OS was 7.2 months versus 9.6 months and 2.4 years versus 4.2 years for the no maintenance and maintenance groups, respectively. On exploratory analysis of the individual regimens, ultraviolet therapy was associated with improved OS (HR, 0.21; P = .034) and PFS (HR, 0.26; P = .002) compared with no maintenance.

Conclusion: Among the patients with CTCL who had received TSEB therapy, maintenance therapy improved PFS for all patients, and ultraviolet-based maintenance improved both PFS and OS in a subset of patients.
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http://dx.doi.org/10.1016/j.clml.2020.06.020DOI Listing
November 2020

Comparison of Access to Novel Drugs for Lymphoma and Chronic Lymphocytic Leukemia Between India and the United States.

JCO Glob Oncol 2020 07;6:1124-1133

Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.

This review will compare and contrast the costs and access to novel drugs for treating chronic lymphocytic leukemia (CLL) and lymphoma in the United States and India during the last 5 years. Clinical outcomes for patients with hematologic malignancies have improved significantly since the approval of immunotherapeutic and targeted therapies. These new treatments have had an impact on overall outcomes and have helped determine the design for translational research and future trials. Although most of these novel drugs called "innovators" are initially approved and marketed in the United States, several have also become available in countries such as India. With the expiration of patents, generic versions of innovator drugs have increased and accessibility has improved for patients. The advent of biosimilars is another route for expanding access to biologic compounds. As a result, the development costs for developing these drugs are lower, and consequently, the costs for the patient are often lower. Although the delivery of cancer care is not the same in India as it is in the United States, the introduction of biosimilars and generics has helped bridge the gap. This has made treatment of CLL and lymphoma similar in both countries and has had the same impact on patient outcomes and quality of life. Compulsory licensing for essential medications, as stipulated by the Doha Declaration, and capping of drug prices could improve global access to treatments for CLL and lymphoma.
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http://dx.doi.org/10.1200/GO.20.00012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392782PMC
July 2020

Strategies for Overcoming Disparities for Patients With Hematologic Malignancies and for Improving Enrollment on Clinical Trials.

Oncology (Williston Park) 2020 Jun;34(6):216-223

A multitude of factors contribute to cancer disparities, including, but not limited to, differences in diet, lifestyle, environmental exposures, cultural beliefs, genetic and biological factors related to ancestry, socioeconomic status (SES), and access to health care. More investigation is needed in evaluating these factors in less common cancers and hematological malignancies. Addressing disparities in cancer incidence, prevalence, burden of disease, mortality, and survivorship that have been documented among racial/ethnic minority populations with blood cancers will require multilevel models of the interactions between relevant factors and performance of translational research that uses knowledge of cancer biology to develop and test the feasibility of interventions that can impact human end points. Such work must address a wide range of research areas, including prevention, early detection, diagnosis, treatment, epidemiology, cancer control, treatment, and survivorship. To be effective, efforts should be made to advance these research findings to applications that can transform clinical practice and health care delivery. We reviewed the literature to define a framework for overcoming disparities for patients with hematologic malignancies and to improve patient enrollment on clinical trials.
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June 2020
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