ABSTRACT
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively studied adults with newly diagnosed MCL treated from 2000 to 2015. Primary objectives were to describe progression-free survival (PFS) and overall survival (OS). Secondary objectives included characterization of patient characteristics and treatments. Of the 1029 patients with MCL studied, a total of 207 neoplasms were blastoid or pleomorphic variants. Median follow-up period was 82 months (range, 0.1-174 months); median PFS was 38 months (95% confidence interval [CI], 28-66) and OS was 68 months (95% CI, 45-96). Factors associated with PFS were receipt of consolidative autologous hematopoietic transplantation (auto-HCT; hazard ratio [HR], 0.52; 95% CI, 0.31-0.80; P < .05), MCL International Prognostic Index (MIPI) intermediate (HR, 2.3; 95% CI, 1.2-4.3; P < .02) and high (HR, 3.8; 95% CI, 2.0-7.4; P < .01) scores, and complete response to induction (HR, 0.29 (95% CI, 0.17-0.51). Receipt of auto-HCT was not associated with OS (HR, 0.69; 95% CI, 0.41-1.16; P = .16) but was associated with MIPI intermediate (HR, 5.7; 95% CI, 2.5-13.2; P < .01) and high (HR, 10.8; 95% CI, 4.7-24.9; P < .01) scores. We report outcomes in a large cohort of patients with blastoid/pleomorphic variant MCL. For eligible patients, receipt of auto-HCT after induction was associated with improved PFS but not OS. Higher MIPI score and auto-HCT ineligibility were associated with worse survival.
Subject(s)
Lymphoma, Mantle-Cell , Adult , Humans , Lymphoma, Mantle-Cell/therapy , Lymphoma, Mantle-Cell/drug therapy , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Risk Assessment , Progression-Free SurvivalABSTRACT
BACKGROUND: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. PATIENTS AND METHODS: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. RESULTS: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. CONCLUSIONS: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.
Subject(s)
COVID-19 , Neoplasms , BNT162 Vaccine , COVID-19 Vaccines , Humans , Neoplasms/drug therapy , Prospective Studies , RNA, Messenger , SARS-CoV-2Subject(s)
Cancer Care Facilities , Neoplasms , Academic Medical Centers , Goals , Humans , Motivation , Neoplasms/therapy , United StatesABSTRACT
PURPOSE: Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)-directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity. METHODS: Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy. RESULTS: Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes. CONCLUSION: To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/therapy , Positron Emission Tomography Computed Tomography , Radioimmunotherapy , Radiopharmaceuticals/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy/adverse effects , Chemoradiotherapy/mortality , Clinical Decision-Making , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Disease Progression , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Female , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Staging , Patient Selection , Predictive Value of Tests , Prednisone/adverse effects , Prednisone/therapeutic use , Prospective Studies , Radioimmunotherapy/adverse effects , Radioimmunotherapy/mortality , Radiopharmaceuticals/adverse effects , Rituximab/adverse effects , Rituximab/therapeutic use , Time Factors , Treatment Outcome , United States , Vincristine/adverse effects , Vincristine/therapeutic use , Young AdultSubject(s)
Coronavirus Infections/epidemiology , Neoplasms/diagnosis , Neoplasms/therapy , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , Delivery of Health Care/organization & administration , Health Resources/supply & distribution , Humans , Medical Oncology/organization & administration , Pandemics , SARS-CoV-2 , Time-to-TreatmentABSTRACT
Over the past several decades, tremendous progress has been made in the treatment of follicular lymphoma. The addition of rituximab to chemotherapy led to significant improvements in survival in the 1990s. Current standard of care in advanced-stage, previously untreated follicular lymphoma is rituximab plus chemotherapy, sometimes followed by rituximab maintenance. Now, as more research is conducted in the field of chemotherapy-free treatment, Dr. Richard I. Fisher discussed the importance of carefully constructed phase II or III trials at the NCCN 2019 Annual Congress: Hematologic Malignancies. He maintained that a nonchemotherapy treatment regimen comprising rituximab + lenalidomide can be considered in carefully selected patients, and that it is currently the only chemotherapy-free treatment that should be recommended.
Subject(s)
Lymphoma, Follicular/drug therapy , Female , Humans , MaleABSTRACT
PURPOSE: Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma. PATIENTS AND METHODS: Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety. RESULTS: Between 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common (P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm. CONCLUSION: In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cyclophosphamide/pharmacology , Cyclophosphamide/therapeutic use , Disease-Free Survival , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Etoposide/pharmacology , Etoposide/therapeutic use , Female , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Prednisone/pharmacology , Prednisone/therapeutic use , Progression-Free Survival , Vincristine/pharmacology , Vincristine/therapeutic use , Young AdultABSTRACT
BACKGROUND: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are frequently expressed in T-cell lymphomas. This provides a rationale for exploration of immune checkpoint inhibitors in the management of T-cell lymphomas. PATIENTS AND METHODS: In this phase II single-arm multicenter trial, patients with relapsed or refractory systemic T-cell lymphoma were treated with 200 mg pembrolizumab intravenously every 21 days. The primary endpoint was progression-free survival (PFS). The secondary endpoints were response rate, overall survival, response duration, and safety. We assessed PD-L1, p-AKT expression, and peripheral blood immune cells as potential predictive biomarkers. RESULTS: Of 18 enrolled patients, 13 were evaluable for the primary endpoint. The trial was halted early after a preplanned interim futility analysis. The overall response rate was 33% (95% confidence interval [CI], 9%-55%); 4 patients achieved a complete response (27%; 95% CI, 5%-49%). The median PFS was 3.2 months (95% CI, 1.2-3.7 months), and the median overall survival was 10.6 months (95% CI, 3.2-100 months). The median duration of response was 2.9 months (95% CI, 0-10.1 months). Two of the 4 complete responders remain in remission > 15 months. Rash was the most common adverse event (17%; n = 3). The most common ≥ grade 3 treatment-emergent adverse events were rash and pneumonitis (11%; n = 2 each). Neither PD-L1 nor p-AKT expression were associated with outcomes. However, a higher relative frequency of CD4+ T lymphocytes pre-treatment was associated with improved PFS (hazard ratio, 0.15; 95% CI, 0.03-0.74). CONCLUSION: Pembrolizumab demonstrated modest single-agent activity in relapsed or refractory T-cell lymphoma.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Lymphoma, T-Cell, Peripheral/etiology , Lymphoma, T-Cell, Peripheral/metabolism , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Biomarkers, Tumor , Drug Resistance, Neoplasm , Female , Humans , Kaplan-Meier Estimate , Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/therapy , Male , Middle Aged , Proto-Oncogene Proteins c-akt/metabolism , Recurrence , Treatment Outcome , Young AdultABSTRACT
PURPOSE: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed. RESULTS: Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION: In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Lymphoma, Mantle-Cell/therapy , Rituximab/therapeutic use , Adult , Age Factors , Aged , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Lymphoma, Mantle-Cell/mortality , Lymphoma, Mantle-Cell/pathology , Male , Middle Aged , North America , Progression-Free Survival , Retrospective Studies , Risk Assessment , Risk Factors , Rituximab/adverse effects , Time Factors , Transplantation, Autologous , Young AdultABSTRACT
Phase II data suggest a benefit to autotransplantation for aggressive T-cell non-Hodgkin lymphoma (T-NHL) in first remission; randomized trials have yet to validate this. We performed a retrospective analysis of aggressive T-NHL patients in the intergroup randomized consolidative autotransplant trial (SWOG 9704). Of the 370 enrolled, 40 had T-NHL: 12 were not randomized due to ineligibility (n = 1), choice (n = 2), or progression (n = 9), leaving 13 randomized to control and 15 to autologous stem cell transplantation (ASCT). Two ASCT patients refused transplant and one failed mobilization. The 5-year landmark PFS/OS estimates for ASCT vs. control groups were 40% vs. 38% (p = .56), and 40% vs. 45% (p = .98), respectively. No difference was seen based on IPI, or histologic subtype. Only 1/7 receiving BCNU-based therapy survived vs. 4/5 receiving TBI. Aggressive T-NHL autotransplanted in first remission did not appear to benefit from consolidative ASCT. This and the 30% who dropped out pre-randomization mostly to progression, suggests that improved induction regimens be developed.
Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, T-Cell/therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Lymphoma, T-Cell/diagnosis , Male , Middle Aged , Neoplasm Staging , Transplantation, Autologous , Treatment Outcome , Young AdultABSTRACT
INTRODUCTION: Copanlisib is a phosphoinositol 3-kinase (PI3K) inhibitor approved for the third-line treatment of follicular non-Hodgkin lymphoma. Although the drug is generally well-tolerated, it can be associated with several unique and potentially serious adverse effects (AEs). Two of the most common toxicities not seen with other PI3K inhibitors include hyperglycemia and hypertension, which primarily occur during infusion and resolve shortly thereafter, and likely relate to targeting the PI3K alpha isoform. Other toxicities less commonly observed with copanlisib than with other approved drugs in this class include non-infectious pneumonitis, infections, diarrhea and colitis, and hepatobiliary toxicity. MATERIALS AND METHODS: A panel composed of experts in lymphoma, diabetes, and hypertension convened to develop guidance pertaining to the administration of copanlisib and the management of the AEs associated with copanlisib treatment. RESULTS: Recommendations were formulated pertaining to the management of AEs associated with copanlisib treatment, particularly infusion-related hyperglycemia and hypertension, noninfectious pneumonitis, infections, diarrhea, and colitis. The recommendations herein reflect the consensus of the members of this panel, all of whom contributed to these suggested approaches to patient supportive care. CONCLUSION: There are a number of challenges associated with the use of copanlisib. Infusion-related hypertension and hyperglycemia occur frequently, although they are transient, reversible, and rarely of clinical significance; this report provides guidance as to their management.
Subject(s)
Antineoplastic Agents/therapeutic use , Drug-Related Side Effects and Adverse Reactions/therapy , Lymphoma, Non-Hodgkin/drug therapy , Pyrimidines/adverse effects , Quinazolines/adverse effects , Antineoplastic Agents/pharmacology , Humans , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Quinazolines/pharmacology , Quinazolines/therapeutic useABSTRACT
BACKGROUND: Despite an abundance of therapeutic options, advanced-stage follicular lymphoma remains incurable. Furthermore, the ideal sequence and absolute benefit of post-induction therapy is unclear. We designed SWOG S0801 to assess the efficacy and safety of consolidative radioimmunotherapy and sequential maintenance rituximab following chemoimmunotherapy. METHODS: For this single-arm, phase 2, multicentre study, we enrolled patients aged 18 years and older with a diagnosis of stage III, IV, or bulky stage II follicular lymphoma, grades 1, 2, or 3a, who had not received previous therapy, from from 20 institutions within the United States National Cancer Institute Clinical Trials Network. Patients were assigned to a 5-year treatment plan consisting of R-CHOP (rituximab plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2], and prednisone or prednisolone [100 mg]) every 21 days for up to six cycles, with rituximab 375 mg/m2 given on day 1 of cycles 1-4, followed by 131iodine tositumomab radioimmunotherapy and subsequent maintenance rituximab 375 mg/m2 within 12 weeks after the sixth cycle of R-CHOP, every 3 months for up to 4 years. The primary endpoint was 3-year progression-free survival in the intention-to-treat population. Efficacy and safety analyses were done in the intention-to-treat population and the per-protocol population. This trial was registered with ClinicalTrials.gov, number NCT00770224. FINDINGS: Between April 1, 2009, and Dec 15, 2010, we enrolled 84 evaluable patients, of whom 73 completed R-CHOP and radioimmunotherapy. Of 69 patients who registered to maintenance therapy, only 41 completed the 4-year rituximab maintenance treatment. Progression-free survival at 3 years was 90% (95% CI 82-95). The most common grade 3 or worse adverse events included neutropenia in 48 (57%) patients, leucopenia in 34 (40%) patients, thrombocytopenia in 17 (20%) patients, and febrile neutropenia in 14 (17%) patients. Nine patients had possible treatment-related deaths during the study from secondary or unknown causes (n=3), cirrhosis (n=1), cardiac arrest (n=1), and secondary malignancies (n=4). Secondary malignancies occurred in seven patients, including two sarcomas, two colorectal carcinomas, two acute myelogenous leukaemias, and one case of renal-cell carcinoma. INTERPRETATION: SWOG S0801 showed near universal responses following chemoimmunotherapy and radioimmunotherapy. However, most discontinuations occurred during maintenance therapy, suggesting that rituximab over a 4-year span is not feasible for many patients. Nonetheless, this sequential therapeutic strategy resulted in good overall outcomes for patients, including a low incidence of early disease progression. FUNDING: The National Cancer Institute and GlaxoSmithKline.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/therapy , Radioimmunotherapy , Rituximab/therapeutic use , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived/adverse effects , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow/pathology , Combined Modality Therapy , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Female , Humans , Induction Chemotherapy , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/mortality , Maintenance Chemotherapy , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Positron-Emission Tomography , Prednisone/adverse effects , Prednisone/therapeutic use , Radioimmunotherapy/methods , Rituximab/administration & dosage , Rituximab/adverse effects , Survival Analysis , Tomography, X-Ray Computed , Treatment Outcome , Vincristine/adverse effects , Vincristine/therapeutic useABSTRACT
Based on promising pilot data a phase II tandem autologous hematopoietic stem cell transplant (AHSCT) trial for relapsed/refractory Hodgkin lymphoma (HL) was performed in the US intergroup setting to determine if long-term progression-free survival (PFS) could be improved. Patients were enrolled after salvage therapy and stem cell collection. Sensitivity to salvage was defined by 1999 Standardized Response Criteria and did not include fluorodeoxyglucose-positron emission tomography. Cycle 1 consisted of melphalan 150 mg/m2 with half of the stem cells. For stable disease or better, patients received cycle 2 consisting of single doses of etoposide 60 mg/kg and cyclophosphamide 100 mg/kg and either total body radiation 12 Gy in 8 fractions over 4 days or BCNU 150 mg/m2/day for 3 days with the remaining stem cells. Of 98 enrolled patients, 89 were eligible and treated: 82 completed both cycles of AHSCT, 47 (53%) had primary refractory HL, and 72 (81%) were resistant to salvage therapy. There were no treatment-related deaths in the first year after AHSCT. With a median follow-up of 6.2 years (range, 2 to 7.7) for eligible patients who remained alive, the 2-year and 5-year PFS were 63% (95% CI, 52% to 72%) and 55% (95% CI, 44% to 64%) respectively; the 2-year and 5-year overall survival were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Univariate Cox regression analysis showed Zubrod performance status and lactate dehydrogenase levels > 1 times upper limit of normal at the time of enrollment were significantly associated with PFS. The observed 5-year PFS of 55% suggests the tandem approach appears to be effective in treating HL patients demonstrated to have poor prognosis in prior single AHSCT trials. This trial was registered at www.clinicaltrials.gov as NCT00233987.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease/therapy , Adult , Aged , Autografts , Child , Cyclophosphamide/administration & dosage , Disease-Free Survival , Etoposide/administration & dosage , Female , Hodgkin Disease/diagnostic imaging , Hodgkin Disease/mortality , Humans , Male , Melphalan/administration & dosage , Middle Aged , Positron-Emission Tomography , Recurrence , Survival Rate , Whole-Body IrradiationABSTRACT
Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133-tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/drug therapy , Radioimmunotherapy/methods , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cause of Death , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Female , Follow-Up Studies , Humans , Lymphoma, Follicular/mortality , Male , Middle Aged , Neoplasms, Second Primary/epidemiology , Prednisone/administration & dosage , Prednisone/therapeutic use , Prognosis , Rituximab , Vincristine/administration & dosage , Vincristine/therapeutic useABSTRACT
Loss of major histocompatibility Class II expression (MHCII) in diffuse large B-cell lymphoma (DLBCL) correlates with decreased survival. MHCII transcription is in part regulated by histone acetylation. We tested the hypothesis that combination of histone deacetylase inhibitor (HDACI) with standard chemotherapy would improve outcomes in DLBCL in part through increased MHCII expression. S0806 was a single arm phase I/II trial of vorinostat given at 400 mg po daily on days 1-9 (subsequently amended to days 1-5 due to toxicity), combined with R-CHOP given on day 3 of a 21-day cycle for 8 cycles, with primary phase II endpoint of 2-year progression free survival (PFS). With 72 evaluable patients, at median follow up of 3 years, 2-year PFS estimate was 73%, and OS estimate was 86%. Considering that the regimen fell short of predefined efficacy improvement and was associated with high rates of febrile neutropenia (38%) and sepsis (19%), it cannot be recommended for general use. Consistent with our hypothesis, patients with low MCHII expression on S0806 had numerically superior outcomes compared to those from trial S0433 which did not use an HDACI, but the difference was not statistically significant. Current studies are focused on finding biomarkers of response to HDACI.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cytokines/blood , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Febrile Neutropenia/etiology , Febrile Neutropenia/immunology , Female , Follow-Up Studies , HLA-D Antigens/biosynthesis , Histone Deacetylase Inhibitors/administration & dosage , Histone Deacetylase Inhibitors/adverse effects , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Prednisone/administration & dosage , Prednisone/adverse effects , Progression-Free Survival , Rituximab/administration & dosage , Rituximab/adverse effects , Sepsis/chemically induced , Sepsis/immunology , Treatment Outcome , Vincristine/administration & dosage , Vincristine/adverse effects , Vorinostat/administration & dosage , Vorinostat/adverse effects , Young AdultABSTRACT
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Comorbidity , Drug Resistance, Neoplasm , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/etiology , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Molecular Targeted Therapy , Neoplasm Staging , Recurrence , Retreatment , Treatment OutcomeABSTRACT
PURPOSE: We describe 7 years of follow-up for the energy/vitality outcome in early-stage Hodgkin's disease patients treated on a randomized clinical trial that compared subtotal lymphoid irradiation (STLI) with combined modality treatment (CMT) (SWOG 9133). Survivorship research questions involved the extent to which symptoms/side effects endured over a follow-up period of 7 years for this early-stage patient group. METHODS: Two hundred thirty-nine patients participated in the quality of life (QOL) companion study (SWOG 9208) and completed the SF-36 vitality scale, SF-36 health perception item, Cancer Rehabilitation Evaluation System-Short Form (CARES-SF), and symptom distress scale. This paper reports vitality outcome results obtained from randomization, 6 months, and annually for 7 years. To assess changes in vitality over time, we used linear mixed models with patient as a random effect. RESULTS: Patients receiving CMT had lower observed vitality at 6 months than did the STLI patients (p < .0001). However, beginning at year 1, vitality results did not differ significantly by treatment over the 5-year (p = .13) and 7-year (p = .16) follow-up periods. Vitality only slightly improved over baseline in either group after treatment. The results were similar after accounting for patterns of recurrence and missing data. CONCLUSIONS: This study demonstrated that patients with early-stage Hodgkin's disease experience a short-term (at 6 months) decrease in vitality with treatment, which is more severe with CMT, but that after the first year, vitality scores were similar between the two treatment groups. Enduring fatigue results for patients receiving these therapies were not observed. Implications for cancer survivors These data provide comprehensive 7-year follow-up vitality information, an important symptom for early-stage lymphoma survivors.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/radiotherapy , Hodgkin Disease/therapy , Lymphatic Irradiation/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hodgkin Disease/pathology , Humans , Male , Middle Aged , Quality of Life , Survivors , Treatment Outcome , Young AdultABSTRACT
Patterns of myeloid growth factor (GF) usage and febrile neutropenia (FN) were examined in patients >60 years of age with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) enrolled on CALGB 9793/ECOG-SWOG 4494, receiving initial therapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab + CHOP (R-CHOP). Myeloid GFs were administered to 256/520 (49%) patients. Indications for use were: prevent dose reduction/dose delay (81%, 207/256); treat FN or non-febrile neutropenia (NFN) (19%, 48/256). One or more FN episodes occurred in 41% (212/520) of patients, with FN most often in cycle 1 (38% of episodes). In multivariate analysis, risk factors for FN included age >65 years (odds ratio (OR) = 2.6, 95% CI: [1.4, 4.9]) and anemia (hemoglobin <12 g/dl) (OR =2.2, 95% confidence intervals (CI): [1.4, 3.5]. Myeloid GF use was common in this older DLBCL population receiving CHOP-based therapy, as was FN, especially during cycle one. Risk factors predictive for FN should be used prospectively to identify patients for whom myeloid GFs are best utilized.