Summary Background Endogenous or iatrogenic antitumour immune responses can improve the course of follicular lymphoma, but might be diminished by immune checkpoints in the tumour microenvironment. ...These checkpoints might include effects of programmed cell death 1 (PD1), a co-inhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells. We did this phase 2 trial to investigate the activity of pidilizumab, a humanised anti-PD1 monoclonal antibody, with rituximab in patients with relapsed follicular lymphoma. Methods We did this open-label, non-randomised trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Adult (≥18 years) patients with rituximab-sensitive follicular lymphoma relapsing after one to four previous therapies were eligible. Pidilizumab was administered at 3 mg/kg intravenously every 4 weeks for four infusions, plus eight optional infusions every 4 weeks for patients with stable disease or better. Starting 17 days after the first infusion of pidilizumab, rituximab was given at 375 mg/m2 intravenously weekly for 4 weeks. The primary endpoint was the proportion of patients who achieved an objective response (complete response plus partial response according to Revised Response Criteria for Malignant Lymphoma). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00904722. Findings We enrolled 32 patients between Jan 13, 2010, and Jan 20, 2012. Median follow-up was 15·4 months (IQR 10·1–21·0). The combination of pidilizumab and rituximab was well tolerated, with no autoimmune or treatment-related adverse events of grade 3 or 4. The most common adverse events of grade 1 were anaemia (14 patients) and fatigue (13 patients), and the most common adverse event of grade 2 was respiratory infection (five patients). Of the 29 patients evaluable for activity, 19 (66%) achieved an objective response: complete responses were noted in 15 (52%) patients and partial responses in four (14%). Interpretation The combination of pidilizumab plus rituximab is well tolerated and active in patients with relapsed follicular lymphoma. Our results suggest that immune checkpoint blockade is worthy of further study in follicular lymphoma. Funding National Institutes of Health, Leukemia and Lymphoma Society, Cure Tech, and University of Texas MD Anderson Cancer Center.
Highlights • Cardiac biomarkers, particularly BNP, can be part of an effective screening strategy for anthracycline-related cardiotoxicity. • In this study, LVEF did not appear to be adequate for the ...detection of cardiotoxicity. • BNP may allow us to direct cardioprotective therapy. More analysis with high-sensitivity troponin is needed.
Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is ...controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL.
We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model.
The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP-based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio HR = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥ 36 Gy (P=.71 PFS and P=.31 OS).
Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.
Abstract Purpose The population of patients aged 80 years or older who are diagnosed with diffuse large B-cell lymphoma (DLBCL) continues to increase, but an optimal treatment strategy has not been ...established. We sought to examine the influence of consolidative radiation therapy (RT) on outcome and toxicity among the very elderly diagnosed with stage I-IV DLBCL. Methods and materials We evaluated 131 patients treated at a single institution between 2002 and 2014 who were eligible for RT after successful treatment with chemotherapy. Results The median age was 83 years (range, 80-96). Advanced-stage disease was present in 61.8% of patients. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone was administered to 80% of patients (n = 108), and 23.7% of patients received consolidative RT. Among early-stage (ES) patients treated with 3 to 4 cycles of chemotherapy and RT (n = 12) versus 6 to 8 cycles of chemotherapy alone (n = 17), there were no statistically significant differences in 3-year disease-free, progression-free, or overall survival rates. The 3 year disease-free survival was 91.7% versus 88.2% among patients treated with combined modality therapy versus chemotherapy alone ( P = .78). The 3-year overall survival was 82.5% versus 87.5% among patients treated with combined modality therapy compared with chemotherapy alone ( P = .852). Anemia and neuropathy occurred more frequently among ES patients who received 6 to 8 cycles of chemotherapy alone. Among advanced-stage patients with bulky disease (n = 35), consolidative RT to sites of bulky disease may have improved local control (3-year local control, 100% vs 60.3%, P = .160). Conclusions Among patients aged 80 years or older who have with ES DLBCL, 3 to 4 cycles of chemotherapy followed by RT is at least equivalent in efficacy to chemotherapy alone and is associated with lower levels of toxicity, which suggests that it may be a better choice for therapy when trying to balance treatment efficacy and tolerability.
Abstract Background For patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL), whole-brain radiation therapy (WBRT) to doses of ≥45 Gy are often given after a ...partial response (PR) to methotrexate-based induction chemotherapy. We conducted an exploratory analysis to determine whether lower-dose WBRT, given with a boost to sites of persistent disease, might be a reasonable alternative. Methods and materials We retrospectively reviewed the records of 22 patients with PCNSL who received WBRT, with or without a boost, after methotrexate-based induction chemotherapy. Outcomes were compared among patients according to response to chemotherapy using the Kaplan-Meier method. Results Median follow-up was 52 months. All patients with a complete response (CR) (n = 5) received WBRT to 23.4 Gy. One CR patient died after an in-field relapse. Patients with partial response (PR) (n = 10) received a median whole-brain dose of 23.4 Gy with (n = 8) or without (n = 2) a boost; there were 2 relapses within the central nervous system (CNS). All PR patients were alive at the time of analysis. The overall survival ( P = .127) and freedom from relapse within the CNS ( P = .967) were not different for patients with CR versus PR. Baseline and follow-up neurocognitive evaluations were available for 4 PR patients, and there were no significant differences between pre- and post-treatment evaluations ( P > .05 for language, memory, visual-spatial, attention, or motor functions). All patients who progressed or did not respond to chemotherapy and then received WBRT had died at a median time of 3.4 months. Patients who progressed or did not respond to chemotherapy had worse overall survival ( P = .001) and freedom from CNS relapse ( P = .005) compared with CR patients. Conclusions Among patients with a PR to induction chemotherapy, reduced-dose WBRT with a boost to residual PCNSL may be a viable treatment approach that merits further investigation.
To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of ...therapy (chemotherapy with or without radiation therapy).
We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings.
Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET-) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET- versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET- vs 52% PET+ P=.012, OS 78% for PET- and 51% for PET+ P=.0055) but not for those who received consolidation radiation therapy (PFS 84% PET- vs 81% PET+ P=.88; OS 90% PET- vs 81% PET+ P=.39).
Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.
We assessed the efficacy of radiation therapy (RT) in the management of secondary central nervous system (CNS) lymphoma.
The cohort comprised 44 patients with systemic diffuse large B-cell lymphoma ...(DLBCL) secondarily involving the brain and/or leptomeninges at initial diagnosis or relapse that was treated with RT.
Of these patients, 29 (66%) were in systemic remission when CNS disease was diagnosed. The overall response rate to RT by magnetic resonance imaging was 88% (42% complete, 46% partial). The median overall survival (OS) after RT initiation was 7 months (95% confidence interval 4-10 months). The OS curve plateaued at 31% from 2 to 8 years. OS was superior in patients who achieved a complete or partial response to RT, underwent stem cell transplantation after RT, and had brain parenchymal (vs leptomeningeal) disease. Eight cases of CNS disease progression occurred after RT: 1 involved the brain parenchyma, and 7 involved the spine and/or cerebrospinal fluid and/or meninges.
We conclude that RT is associated with high response rates and may contribute to long-term OS. In addition, RT may provide CNS disease control that facilitates successful salvage with stem cell transplantation in patients with chemotherapy-refractory disease.
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