Papers by Narendranath Epperla
Journal of Hematology & Oncology, Jan 10, 2019
Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantati... more Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT. Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000-2016.
Hematological Oncology, Oct 6, 2022
The management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes admini... more The management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes administration of high‐dose methotrexate based regimens followed by consolidation therapy to minimize the risk of relapse. However, the best consolidation strategy (autologous hematopoietic cell transplant [auto‐HCT] vs. whole‐brain radiotherapy [WBRT]) is controversial. Hence, we performed a systematic review and meta‐analysis of all randomized controlled trials that compared auto‐HCT versus WBRT consolidation for patients with PCNSL after first‐line treatment.The primary outcome was overall survival (OS), while the secondary outcomes included progression‐free survival (PFS), response rates (overall response rate [ORR] and complete remission [CR]), relapse rate, treatment‐related mortality (TRM), and neuropsychological adverse events. We performed a pooled analysis of the single‐arm studies that incorporated auto‐HCT or WBRT consolidation and evaluated neurocognitive outcomes. Only two studies met the inclusion criteria (n = 240). There was no significant difference in OS (HR = 1.50; 95% CI = 0.95–2.36), PFS (HR = 0.99; 95% CI = 0.44–2.22), ORR (RR = 1.48; 95% CI = 0.90–2.44), CR rate (RR = 1.21; 95% CI = 0.90–1.63), relapse rate (RR = 0.46; 95% CI = 0.05–4.28), and TRM (RR = 5.67; 95% CI = 1.01–31.91). The neuropsychological tests to assess neurocognitive domains were different and inconsistently reported in the two studies and therefore we were unable to perform a meta‐analysis but provide a descriptive assessment. Both the studies showed a significant decline in the attention/executive function (based on the trail making test A and trail making test B) in those receiving WBRT compared to auto‐HCT. We found 9 single‐arm phase II studies that reported data on outcomes associated with either auto‐HCT (5 studies) or WBRT (4 studies) consolidation. Of these, two studies (n = 43) reported data on neurocognitive decline following auto‐HCT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 6% (95% CI, 0%–17%) for those receiving auto‐HCT and there was no heterogeneity between studies (I2 = 0%). Three studies (n = 122) reported data on neurocognitive decline following WBRT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 43% (95% CI, 11%–78%) for those receiving WBRT and there was high heterogeneity between studies (I2 = 94%). There was significant heterogeneity between subgroups (p = 0.035). The outcomes were not significantly different in patients with PCNSL receiving auto‐HCT or WBRT consolidation therapies, however, there is a higher degree of neurocognitive decline associated with WBRT compared to auto‐HCT consolidation. The decision to choose a consolidation strategy needs to be individualized based on age, frailty, and co‐morbidities.
Clinical Medicine & Research, Aug 4, 2011
Apical hypertrophic cardiomyopathy (AHC) is a rare variant of hypertrophic cardiomyopathy. Since ... more Apical hypertrophic cardiomyopathy (AHC) is a rare variant of hypertrophic cardiomyopathy. Since its description by Sakamoto in 1976 in Japanese patients, our understanding of this entity has evolved. Although cardiac magnetic resonance imaging has emerged as the gold standard for diagnosing AHC, clinical attention must be drawn to the unique electrocardiographic features that provide the initial clues to making the diagnosis. In this case, we present a 47-year-old man with AHC who presented with recurrent syncope, but anomalies on his electrocardiogram went unnoticed on two clinical encounters. He was subsequently admitted to our service and rapidly diagnosed after we observed the very classical findings in the plain twelve lead electrocardiogram done at the time of admission. In a clinical encounter involving a patient presenting with recurrent syncope, special attention must be focused on the electrocardiogram to decipher the unique diagnostic features it might show.
American Journal of Hematology, May 17, 2016
British Journal of Haematology, Apr 25, 2017
Ig G j, bone marrow infiltration of 20% and high serologic disease activity (serum free j light c... more Ig G j, bone marrow infiltration of 20% and high serologic disease activity (serum free j light chains, 14 015 mg/l; patient #4).
Transplantation and Cellular Therapy, Jul 1, 2023
Journal of Clinical Oncology, Jun 1, 2023
Holland‐Frei Cancer Medicine, Oct 21, 2022
American Journal of Hematology, Feb 3, 2021
included the crude probability of MZL-specific death in the presence of competing risks [also kno... more included the crude probability of MZL-specific death in the presence of competing risks [also known as the MZL-specific cumulative incidence function (CIF)] and overall survival (OS). RS was defined as the ratio of all-cause to expected survival following diagnosis of MZL and was estimated using a model-based approach rather than a nonparametric approach. MZL-specific CIF was defined as the probability of dying from MZL following diagnosis of the disease in the presence of the competing risk of death from other causes. OS was defined as the CORRESPONDENCE E125 CONFLICT OF INTEREST JLV declares no relevant conflict of interest. LCP declares no relevant conflict of interest. AO declares no relevant conflict of interest. NE has no relevant COI pertaining to the manuscript.
Cancer, Aug 23, 2019
Background/Objective: Nearly 30% of patients with advanced-stage Hodgkin lymphoma (HL) are not cu... more Background/Objective: Nearly 30% of patients with advanced-stage Hodgkin lymphoma (HL) are not cured. We should better control tumors with initial treatment for patients with advanced stage HL whose interim positron emission tomography/computed tomography (PET/CT) was positive. The objective of our study was to confirm the superiority of autologous hematopoietic stem cell transplantation (ASCT) therapy in these patients. Methods: Eighty-nine HL patients with stage III-IV, international prognostic score (IPS) ≥3 and Deauville more than 3°at the interim PET/CT were analyzed. Forty five patients received ASCT. The other 44 patients received two cycles DHAP chemotherapy. Results: The 3-year overall survival (OS) of patients who received ASCT was 91.1%, and for the patients who received chemotherapy, it was 72.7% (P = 0.025). The 3-year progression free survival (PFS) of patients in the ASCT group was 88.9%, but for patients in the chemotherapy group, it was only 70.5%(P = 0.017). No patient died of toxicity from ASCT. Additionally, there was no difference in the rates of secondary malignancies between the ASCT and chemotherapy groups. Extranodal and bone marrow involvement were poor prognostic factors, while ASCT was a good prognostic factor. Conclusion: The use of ASCT as a first-line consolidation treatment could improve outcome of patients with advanced-stage high risk HL whose interim PET/CT was positive.
Leukemia Research, Oct 1, 2022
Blood, Nov 5, 2020
Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL)... more Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses.
Transplantation and Cellular Therapy, Mar 1, 2022
Blood, Nov 5, 2020
Introduction: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non-Hodgkin lymphoma th... more Introduction: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non-Hodgkin lymphoma that usually presents in elderly patients with splenomegaly, lymphocytosis, and cytopenias (either due to hypersplenism or autoimmune phenomena). Treatment of SMZL has advanced over the past decade including identification of better tolerable chemotherapy regimens (such as rituximab and bendamustine) and the advent of novel agents (such as ibrutinib and lenalidomide). We sought to determine whether advances in treatment and supportive care over the past decade have translated to decreased lymphoma-specific mortality among patients with SMZL. Method: We used the population-based Surveillance, Epidemiology, and End Results (SEER)-18 database. We included adult patients with SMZL diagnosed between 2000-2017 who were 18-84 years old at the time of diagnosis. We excluded patients with a history of malignancy prior to SMZL, those with missing survival times and those with central nervous system involvement. Patients were divided into two cohorts based on period of diagnosis (era-1: 2000-2008, and era-2: 2009-2017). Five-year relative survival (RS) was estimated using the Pohar-Perme method. Differences between RS distributions was tested with a log-rank-type test. The risk of SMZL-specific death was estimated by calculating the cumulative incidence function (CIF). The difference between CIF distributions was tested with the Pepe-Mori test. The competing risks of SMZL-specific death and death from other causes were modeled using Fine and Gray regression. All tests of differences were performed at a two-sided alpha of 0.05. Results: We included 1,548 patients with SMZL. Table 1 shows the baseline characteristics. The median age at diagnosis was 66 years (IQR = 57-74) years. Most patients were non-Hispanic White (81%) with advanced stage at diagnosis (stage III-IV, 70%). Five-year RS was 84% (95% CI = 80-87%) during era-1 and 89% (95% CI = 85-92%) during era-2 (p = 0.21. The CIF distributions for SMZL-specific death and death from other causes are shown in Figure 1A and Figure 1B, respectively (Pepe-Mori p = 0.02). In our multivariable competing risks model, the period of diagnosis, age, and stage at diagnosis were significant predictors of SMZL-specific death (Table 2). Patients in era-2 had significantly lower risk of SMZL-specific death [subhazard ratio (SHR) = 0.30, 95% CI = 0.22-0.41), while the cumulative incidence of mortality significantly increased with age (SHR = 1.39 per decade, 95% CI = 1.24-1.56) and advanced stage (SHR = 1.55, 95% CI= 1.04-2.13). Conclusion: There has been a significant reduction in the risk of SMZL-specific death for patients with SMZL in the most recent era possibly due to advances in therapy. This reduction in mortality persists even after accounting for competing risks of mortality from other causes. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding; Genentech, Inc.: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria.
Leukemia & Lymphoma, Sep 7, 2022
Bone Marrow Transplantation, Nov 9, 2018
Blood Cancer Journal, Dec 13, 2022
A significant body of literature has been generated related to the detection of measurable residu... more A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.
Cancer Medicine, Sep 1, 2021
Background: Racial/ethnic disparities in the utilization of hematopoietic cell transplantation (H... more Background: Racial/ethnic disparities in the utilization of hematopoietic cell transplantation (HCT) have been reported for patients with hematologic malignancies, but population-based data are lacking for lymphoma patients. The objective of this study was to determine whether racial and ethnic disparities exist in the utilization of autologous HCT for lymphoma in the United States. We used Surveillance, Epidemiology, and End Results data linked to Medicare fee-for-service claims. We included Medicare beneficiaries aged 66+ years with Hodgkin or Non-Hodgkin lymphomas diagnosed between 2008 and 2015. The primary outcome was time-to-autologous HCT. We used Cox proportional hazards models to estimate racial/ethnic differences in utilization. Missing data were handled using multiple imputation with chained equations. We included 40,605 individuals with lymphoma. A total of 452 autologous transplants were performed. In the unadjusted model, Non-Hispanic Black patients were 51% less likely to receive a transplant than Non-Hispanic White patients (95% CI, 0.26-0.96; p = 0.04). After adjusting for age at diagnosis and sex, Non-Hispanic Black patients were 61% less likely to receive a transplant (95% CI, 0.20-0.76; p = 0.01). However, observed differences attenuated and became non-significant after adjustment for socioeconomic factors (adjusted hazard ratio [aHR], 0.62; 95% CI, 0.32-1.21; p = 0.16) and disease-specific factors (aHR, 0.58; 95% CI, 0.30-1.12; p = 0.11), separately. In the fully adjusted model, we also did not observe a statistically significant association between Non-Hispanic Black race/ethnicity and receipt of transplant (aHR, 0.54; 95% CI, 0.28-1.05; p = 0.07). In this population-based cohort study of lymphoma patients, Non-Hispanic Black patients were less likely to receive autologous HCT compared to Non-Hispanic White patients, but this difference was partially explained by socioeconomic and disease-specific factors.
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Papers by Narendranath Epperla