A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine,Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev)

PurposeTo evaluate the impact of lenalidomide in patients with aggressive lymphoma who experienced less than complete response (CR) or as maintenance therapy after CR after gemcitabine, rituximab, and oxaliplatin salvage chemotherapy (GROC-Rev regimen).Patients and MethodsPatients with relapsed/refractory non-Hodgkin lymphoma received up to 6 GROC-Rev courses: rituximab (375 mg/m² provided intravenously) on day 1, oxaliplatin (100 mg/m² provided intravenously; 2 hours), gemcitabine (provided 1250 mg/m² intravenously; 30 minutes) on day 2, and pegfilgrastim (6 mg provided subcutaneously) on day 3. Patients switched to lenalidomide if they did not experience at least partial response (PR) after their second GROC-Rev course, or if they experienced less than a CR after 6 courses.ResultsIn 33 patients, overall response was 61% (CR = 39%). Of 17 patients with PR who continued to 6 courses, 10 (59%) experienced CR and 7 PR as maximum response; of these 7, 1 died before receiving lenalidomide, 1 experienced CR while receiving lenalidomide (17%), and 2 experienced a further PR (33%). Of 16 with disease that failed to respond to GROC-Rev after their second course, 2 died before lenalidomide could be administered, and 2 experienced CR (14%) and 1 PR (7%) after lenalidomide. Overall survival and progression-free survival were 47% and 33% at 2 years. Grade 3/4 adverse events included neutropenia, thrombocytopenia, and/or anemia (n = 5), neutropenic infection (n = 3), urinary tract infection (n = 3), pneumonia (n = 2), cellulitis (n = 2), and seizure (n = 1). Eight went on to receive transplants.ConclusionGROC-Rev is an effective and well-tolerated salvage regimen consisting of chemotherapy followed by lenalidomide maintenance in patients with relapsed/refractory non-Hodgkin lymphoma. Simultaneous administration of these agents is worth exploring in future studies.     

Limited Utility of Surveillance Imaging for Detecting Disease Relapse in Patients With Non-Hodgkin Lymphoma in First Complete Remission

IntroductionSurveillance imaging with computed tomography (CT) or positron emission tomography with CT (PET/CT) is commonly used in practice in patients with non-Hodgkin lymphoma (NHL) who are in remission after front-line therapies. We aimed to determine the utility of routine imaging for detecting first relapse in patients with NHL in complete remission (CR) after first-line therapies.Patients and MethodsWe retrospectively analyzed patients with NHL who achieved CR after first-line therapies and then subsequently had disease relapse. We evaluated whether the relapse was detected solely by surveillance CT or PET/CT or by patient-reported symptoms or physical examination findings, or both. Subgroup analysis was performed on baseline histologic type (indolent vs. aggressive NHL). Data were also collected to determine the cost of surveillance PET/CT and the number of additional diagnostic imaging procedures, invasive procedures, and iatrogenic complications directly resulting from an abnormality detected on a surveillance scan.ResultsOne hundred sixty-three patients with first relapse of NHL between January 1, 2000 and December 31, 2010 were included. The majority of the relapses were detected by patient-reported symptoms or physical examination, or both, as opposed to surveillance imaging (77.9% [n = 127] vs. 22.1% [n = 36]; P < .0001). There was no overall survival difference between the 2 groups (P = .66). Patient-reported symptoms led to the detection of the majority of relapses in aggressive (85.7% [n = 72] vs. 14.3% [n = 12]; P < .0001) as well as indolent NHL (69.6% [n = 55] vs. 30.4% [n = 24]; P = .0007). Surveillance PET/CT contributed to more than 75% of follow-up health care costs in the first 2 years of monitoring for relapse. The surveillance imaging group had 1 reported case of iatrogenic pneumothorax.ConclusionOur retrospective analysis suggests that there is a limited role for surveillance imaging by CT or PET/CT in detecting first relapse in NHL. There was no difference in survival outcomes between the 2 groups in our study.     

Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy

BackgroundIn the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC).MethodsAfter four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]).ResultsFollowing first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR; <1% unknown response). Erlotinib maintenance therapy significantly prolonged PFS in both the SD (hazard ratio [HR] = 0.68; P < 0.0001) and CR/PR (HR = 0.74; P = 0.0059) groups, while OS was significantly prolonged in the SD group only (HR = 0.72; P = 0.0019). The erlotinib-related OS benefit in the SD group remained significant across subgroups, irrespective of tumour histology and/or EGFR mutation status. The incidence of adverse events was similar in the SD group and the overall population, and erlotinib treatment did not negatively impact quality of life.ConclusionsPatients with advanced NSCLC and SD following first-line platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy.     

Clinical Outcomes of Fludarabine and Melphalan With an 800 cGy Total Body Irradiation Conditioning Regimen in Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

IntroductionAllogeneic hematopoietic stem cell transplant with reduced-intensity conditioning is an effective therapeutic option for patients with refractory or relapsed aggressive non-Hodgkin lymphoma (NHL).Patients and MethodsWe retrospectively evaluated survival outcomes and the efficacy of our fludarabine/melphalan/total body irradiation (TBI) (FMT) regimen. A total of 89 patients had received the FMT regimen from 2007 to 2017.ResultsThe majority of patients (n = 81; 91%) belonged to the histologic subtype of aggressive NHL. The estimated 3-year overall survival and disease-free survival for the entire cohort during a median follow-up of 31 months were 47.1% (95% confidence interval, 36%-57%) and 45.4% (95% confidence interval, 35%-56%), respectively. The cumulative incidence rates of relapse and non-relapse mortality at 3 years were 33.1% and 13.8%, respectively. In analyses of risk factors affecting survival outcomes, chemosensitive disease status at transplant (hazard ratio [HR], 2.45; P = .010), delayed relapse after first-line chemotherapy (HR, 2.101; P = .009), no grade III to IV acute graft-versus-host disease (HR, 11.212; P < .001), and mild chronic graft-versus-host disease (HR, 0.448; P = .016) were independent significant predictors of favorable overall survival. Also, similar parameters were related to favorable disease-free survival. All non-hematologic toxicities occurred within 50 days after allogeneic hematopoietic stem cell transplant, and most of the adverse events were tolerable and manageable with a < 30% incidence.ConclusionOur FMT regimen shows favorable transplant outcomes with relatively low-risk toxicities, so it may be a promising strategy for patients with relapsed or refractory aggressive NHL.     

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa,Busulfan, and Cyclophosphamide Conditioning Regimen

BackgroundHigh-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and non-Hodgkin lymphoma (NHL) with CNS involvement and has shown promising results.Patients and MethodsA retrospective analysis was performed of 48 consecutive patients who had undergone HDC/ASCT with TBC (thiotepa, busulfan, cyclophosphamide) conditioning for PCNSL (27 patients), secondary CNS lymphoma (SCNSL) (8 patients), or relapsed disease with CNS involvement (13 patients) from July 2006 to December 2017. Of the 27 patients with PCNSL, 21 had undergone ASCT at first complete remission (CR1).ResultsThe 2-year progression-free survival (PFS) rate was 80.5% (95% confidence interval [CI], 69.9-92.9) and the 2-year overall survival (OS) rate was 80.1% (95% CI, 69.2%-92.7%) among all patients. The 2-year PFS and OS rate for patients with PCNSL in CR1 was 95.2% (95% CI, 86.6%-100%) and 95.2% (95% CI, 86.6%-100%), respectively. On univariate analysis of the patients with PCNSL, ASCT in CR1 was the only variable statistically significant for outcome (P = .007 for PFS; P = .008 for OS). Among patients with SCNSL or CNS relapse, the 2-year PFS and OS rate were comparable at 75.9% (95% CI, 59.5%-96.8%) and 75.3% (95% CI, 58.6%-98.6%), respectively. The most common side effects were febrile neutropenia (89.6%; of which 66.7% had an infectious etiology identified), nausea/vomiting (85.4%), diarrhea (93.8%), mucositis (89.6%), and electrolyte abnormalities (89.6%). Four patients (8.3%) died of treatment-related overwhelming infection; of these patients, 3 had SCNSL.ConclusionHDC and ASCT using TBC conditioning for both PCNSL and secondary CNS NHL appears to have encouraging long-term efficacy with manageable side effects.     

Treatment and Outcomes of Primary Breast Lymphoma

PurposeTo evaluate treatment and outcomes in a population-based cohort of patients diagnosed with primary breast lymphoma.Methods and MaterialsPrognostic factors, management, and outcomes (local control, lymphoma-specific survival, and overall survival) were analyzed for all patients diagnosed with limited-stage, primary breast non-Hodgkin lymphoma (n = 50) diagnosed in British Columbia between 1981 and 2009.ResultsThe median follow-up was 3.5 years; 64% presented with a breast mass. Histologic subtypes were indolent (n = 16 [32%]) or aggressive (n = 34 [68%]). Of those with indolent lymphoma, 81% had stage I, and 19% had stage II disease; 13% received no initial treatment; 75% received radiotherapy (RT) alone. One (6%) patient received surgical resection alone, and 1 (6%) patient received surgical resection in addition to RT. Of those with aggressive lymphoma, 62% had stage I and 38% had stage II disease; 3% received no initial treatment; 6%, RT alone; 38%, chemotherapy only; 41%, chemotherapy and RT; 9%, surgical resection alone; and 3%, surgical resection in addition to chemotherapy and RT. In patients with indolent and aggressive disease, 5-year local control estimates were 92% and 96%, lymphoma-specific survivals were 91% and 71%, and overall survivals were 75% and 54%, respectively. On univariate analysis, stage (I vs. II) (P = .006) and RT use (P = .032) were statistically significant predictors of improved overall survival in patients with indolent breast lymphoma. Combined chemoradiation was associated with a trend for improved overall survival (P = .061) in patients with aggressive disease. There were 4 cases of central nervous system relapse, all occurred in subjects with aggressive primary breast lymphoma.ConclusionsPatients with indolent breast lymphoma were most frequently treated with RT alone and achieved high rates of local control and survival. Patients with aggressive histology most often treated with chemotherapy, alone or combined with RT, had excellent local control but lower survival compared with indolent disease. Improved systemic therapies are needed to improve outcomes for patients with aggressive breast lymphoma.     

Effect of Routine Surveillance Imaging on the Outcomes of Patients With Classical Hodgkin Lymphoma After Autologous Hematopoietic Cell Transplantation

BackgroundPatients with relapsed and refractory classical Hodgkin lymphoma (cHL) are often treated with autologous hematopoietic cell transplantation (auto-HCT). After auto-HCT, most transplant centers implement routine surveillance imaging to monitor for disease relapse; however, there is limited evidence to support this practice.Patients and MethodsIn this multicenter, retrospective study, we identified cHL patients (n = 128) who received auto-HCT, achieved complete remission (CR) after transplantation, and then were followed with routine surveillance imaging. Of these, 29 (23%) relapsed after day 100 after auto-HCT. Relapse was detected clinically in 14 patients and with routine surveillance imaging in 15 patients.ResultsWhen clinically detected relapse was compared with to radiographically detected relapse respectively, the median overall survival (2084 days [range, 225-4161] vs. 2737 days [range, 172-2750]; P = .51), the median time to relapse (247 days [range, 141-3974] vs. 814 days [range, 96-1682]; P = .30) and the median postrelapse survival (674 days [range, 13-1883] vs. 1146 days [range, 4-2548]; P = .52) were not statistically different. In patients who never relapsed after auto-HCT, a median of 4 (range, 1-25) surveillance imaging studies were performed over a median follow-up period of 3.5 years.ConclusionA minority of patients with cHL who achieve CR after auto-HCT will ultimately relapse. Surveillance imaging detected approximately half of relapses; however, outcomes were similar for those whose relapse was detected using routine surveillance imaging versus detected clinically in between surveillance imaging studies. There appears to be limited utility for routine surveillance imaging in cHL patients who achieve CR after auto-HCT.     

Effect of response quality and line of treatment with rituximab on overall and disease-free survival of patients with B-cell lymphoma

Background

The introduction of rituximab into the treatment of patients with non-Hodgkin’s lymphomas has improved the overall response rate, as well as the response duration and the overall survival of patients with B-cell lymphomas. But only a few studies have addressed the question whether the better response (complete response) and the early introduction of rituximab into the treatment translate into the better survival. The aim of this retrospective study was to assess the potential relationship between either the quality of the response or the line of the rituximab treatment and the overall survival (OS) as well as the disease-free survival (DFS) of patients with B-cell lymphomas.

Patients and methods.

In the study, we analysed treatment outcomes in patients with different histological types of B-cell lymphomas who were treated at the Institute of Oncology between 2003 and 2007 with rituximab and chemotherapy. We included only patients who had the level of CD20 expression assessed prior to the introduction of the treatment with quantitative flow-cytometric measurements. The OS and DFS were evaluated by Kaplan-Meier survival curves.

Results

One hundred and fourteen patients were enrolled in the study. Patients who achieved a complete response after the rituximab containing treatment had a significantly longer OS than those reaching a partial response (hazard ratio [HR], 0.34; 95% CI, 0.05 to 0.91, P = 0.0375) and than patients with stable (hazard ratio [HR], 0.11; 95% CI, 0.0002 to 0.033, P < 0.0001) or progressive disease (hazard ratio [HR], 0.09; 95% CI, 0.003 to 0.03, P < 0.0001). Patients who achieved a complete response (CR; n = 70; 61.4%) had also a significantly longer DFS (hazard ratio [HR], 0.26; 95% CI, 0.021 to 0.538, P = 0.0068) than those reaching only a partial response (PR; n = 17; 14.9%). Patients treated with rituximab as the first-line treatment (n = 50; 43.9%) had a significantly longer OS than those treated with rituximab for the first (hazard ratio [HR], 0.27; 95% CI, 0.106 to 0.645, P = 0.0036) or second relapse (hazard ratio [HR], 0.22; 95% CI, 0.078 to 0.5, P = 0.0006). Also the DFS of patients treated with rituximab as the first-line treatment (n = 46; 52.9%) was significantly longer (hazard ratio [HR], 0.32; 95% CI, 0.088 to 0.9, P = 0.0325) than in patients treated with rituximab for their first relapse (n = 25; 28.7%).

Conclusions

These data indicate that a better response to rituximab therapy presumably translates into an improved OS and DFS for patients with B-cell lymphomas. The early introduction of rituximab into the treatment (i.e. first-line treatment) might improve OS. Therefore, the response adapted first-line therapy with rituximab should be considered when the treatment decision is taken in B-cell lymphoma patients.     

Autologous Stem Cell Transplantation in Central Nervous System Lymphoma: A Multicenter Retrospective Series and a Review of the Literature

BackgroundCentral nervous system (CNS) lymphoma is associated with poor outcomes. Autologous stem cell transplantation (ASCT) has been reported to improve outcomes when used as a consolidation strategy in primary CNS lymphoma (PCNSL) and as a salvage strategy in patients with disease relapse limited to the CNS. Herein, we describe our experience of using ASCT in PCNSL and secondary CNS lymphoma (SCNSL).Patients and MethodsWe evaluated clinical outcomes of 18 patients from 2 major academic centers with a median age of 55 (range, 46-72) years. Thirteen patients had PCNSL and 5 patients had SCNSL. Most of the cases were in the first (CR1) or second (CR2) complete remission (CR1 = 7, CR2 = 7) at the time of ASCT. Carmustine with thiotepa (n = 12, 67%) was the most commonly prescribed preparative regimen.ResultsThe median follow-up from ASCT for surviving patients was 12 (range, 0.9-115) months. The 2-year progression-free survival (PFS) and overall survival (OS) were 74% (95% confidence interval [CI], 48%-99%) and 80% (95% CI, 55%-100%), respectively. Two-year non-relapse mortality was 0%. The 2-year cumulative incidence of relapse/progression was 27% (95% CI, 10%-72%). In subgroup analysis of PCNSL patients, 2-year PFS, OS, and relapse were 71% (95% CI, 38%-100%), 71% (95% CI, 38%-100%), and 29% (95% CI, 9%-92%), respectively.ConclusionIn this retrospective study of patients with CNS lymphoma, consolidation with ASCT after high-dose methotrexate-based chemotherapy is safe and effective in reducing disease relapse.     

COMBINATION CHEMOTHERAPY WITH COBDP IN MALIGNANT LYMPHOMA: AN ANALYSIS OF 64 CASES

From February 1986 to February 1989, 64 patients with malignant lymphoma were treated with COBDP regimen. Of these patients, there were 7 cases with Hodgkin's disease and 57 cases with non Hodgkin's lymphoma. Clinical staging showed 7 stage Ⅰ , 5 stage Ⅱ, 22 stage Ⅲ and 30 stage Ⅳ . The COBDP regimen was carried out as : Cyclophosphamide 600 mg iv on days 1,8; vincristine 2 mg iv on days 1,8; Pingyanymycin long im on days 1, 4, 8, 11; cis-dichlorodiamineplatinum 20 mg iv drip on day 1 - 5 and prednisone 10 mg po tid on day 1 -14. Treatment results showed 39% (25 cases) achieving complete remission (CR) , 52% (33 cases) partial remission (PR) , giving an over-all response rate of 91 % (CR PR). There was a significant difference in the CR of the untreated patients (56%) and that of the treated ones (28%) (P< 0.05) .However, between two groups of patients, no statistical significance was observed in the median CR duration (> 12 months, vs >9 months) and the median surrivals of the CR patients (> 16. 5     

Clinical characteristics and outcomes of relapsed follicular lymphoma after autologous stem cell transplantation in the rituximab era

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a therapeutic option for patients with relapsed follicular lymphoma (FL). The clinical characteristics and outcomes of FL relapse after ASCT in the rituximab era have not yet been fully elucidated. We retrospectively reviewed 414 FL patients treated with ASCT between 2000 and 2014 in four hematology departments. All patients received rituximab as a first-line treatment. We specifically analyzed the clinical characteristics, treatment strategies at relapse, and outcomes of 95 patients (23%) who relapsed after ASCT. The patients (median age, 57 y) received a median of two lines of therapy (range, 2-6) prior to ASCT, with 92% in complete response (CR) or partial response (PR) before ASCT. Histological transformation at relapse after ASCT was observed in 20% of the patients. Treatment at relapse after ASCT consisted of chemotherapy with or without rituximab (n = 45/90, 50%), targeted agents (18%), rituximab monotherapy (14%), or consolidation allogeneic transplantation after induction chemotherapy (12%) and radiotherapy (6%). After relapse, the median progression-free survival (PFS) and overall survival (OS) were 1 year (95% CI, 0.541-1.579) and 5.5 years (95% CI, 1.910-9.099), respectively. In the multivariate analysis, histological transformation (HT) was associated with OS (P = .044; HR 2.439; 95% CI, 1.025-5.806), and a high FLIPI score at relapse was associated with PFS (P = .028; HR 2.469; 95% CI, 1.104-5.521). This retrospective study showed that the period of PFS of patients who relapsed after ASCT is short. A biopsy should be performed for these patients to document the HT. Our results indicate that new treatment strategies will need to be developed for these patients.     

Treatment of human immunodeficiency virus-associated hodgkin disease is there a clue regarding the cause of hodgkin disease?

Background. The occurrence of human immunodeficiency virus (HIV)-associated Hodgkin disease (HD) offers a unique opportunity to study the cause of HD and compare HIV–HD with the well-characterized HIV–non-Hodgkin lymphoma (NHL). Methods. Eight patients with HIV–HD and 17 with HIV–NHL were treated. Results. The complete remission (CR) rate in HIV–HD was 100% with mechlorethamine, vincristine, procarbazine, and prednisone or doxorubicin, bleomycin, vinblastine, and dacarbazine (median survival, > 38.0 months). HIV–NHL patients were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CR, 80%; median survival, 13.0±1.3 months). Durable CR was achieved with one to six cycles of chemotherapy (median, 4). There were no late relapses. The difference between the survival rate associated with chemotherapy-treated HIV–HD and chemotherapy-treated HIV–NHL approached statistical significance (P = 0.06). Analysis indicated that all patients with HIV–HD (n = 8) may have acquired HIV through intravenous drug abuse (IVDA) compared with 1 of 17 patients with HIV–NHL (P = 0.0001). A combined analysis (metaanalysis) of 157 patients with chemotherapy-treated HIV–NHL and 51 with chemotherapy-treated HIV–HD confirmed the significantly better survival of those with HIV–HD (P < 0.0001). Conclusions. Standard combination chemotherapy, truncated as necessary, offers survival outcomes that are at least equivalent and, perhaps, superior to previously published experimental approaches for HIV–NHL and HIV–HD. HIV–HD has a significantly better prognosis than HIV–NHL and is associated with IVDA. These data suggest that the etiologic agents of HIV–HD and HIV–NHL may be transmissible, identifiable, and unique.     

Factors affecting survival in patients aged 60 and over with diffuse large B cell lymphoma failing first-line therapy

ObjectivesElderly patients with diffuse large B cell lymphoma (DLBCL) without prohibitive co-morbidities may be cured with standard immuno-chemotherapeutic regimens, as used in younger patients. Less is known about the survival prospects in older people, if first-line therapy fails. This study aimed to provide additional information regarding prognosis in this group.Materials and MethodsDatabases were collated from three randomized trials of first-line therapy in those aged 60 and over, deemed fit enough for standard therapy. Overall survival from the point of treatment failure was calculated and comparisons were made between age groups and types of treatment failure.ResultsOverall survival (OS) at 2 years in 862 patients was 46%, 38%, 37% and 23%, respectively, for those aged 60–64, 65–69, 70–74 and > 74. Type of treatment failure impacted on 2 year OS as follows: initial partial remission (PR): 48%; complete response (CR) with late relapse: 37%; CR with early relapse: 17%; and less than PR to initial therapy: 12%.ConclusionOlder patients failing first-line therapy for DLBCL should be counseled differently regarding prognosis depending upon age and type of treatment failure. The chance of survival was greater in those achieving PR or CR with relapse more than 12 months from diagnosis. This data may support the consideration of aggressive salvage therapy in fit patients in these categories, regardless of biological age per se. Palliative management may be more appropriate for those achieving less than PR to initial therapy or who enter CR but relapse within one year of diagnosis.     

Therapeutic results in patients with relapsed diffuse large B cell Non-Hodgkin's lymphoma achieving complete response only after autologous stem cell transplantation

Forty patients with relapsed diffuse large B cell lymphoma (DLBCL) autografted in partial response (PR) (n = 23) or in refractory relapse (RR) (n = 17) achieved complete remission (CR) after autologous stem cell transplantation (ASCT). Salvage treatment consisted of ifosphamide, epirubicin and etoposide (IEV) in 33 patients and Cisplatinum, ARA-C and dexamethasone (DHAP) in 7 patients. All PR and 8 RR patients were conditioned with BEAM, while 9 RR cases received the BCV regimen. There were no significant differences between the two groups as age, serum LDH, duration of CR1 and IPI at relapse are concerned. Relapse rate after ASCT was 39% in PR group as opposed to 88% in RR group (p = 0.003). Median relapse free survival from ASCT was 6 months for RR patients as opposed to 34 months for PR patients (p = 0.003); median overall survival from ASCT was 10 months for RR subset as opposed to not reached for RR subgroup (p = 0.001). These data demonstrate that CR achieved after ASCT in DLBCL patients who are refractory to previous salvage therapy does not result in long-term disease control. Alternative preparative regimens, allogeneic SCT and/or monoclonal antibodies in the post-ASCT phase should be considered for RR patients despite CR achievement.     

Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma and despite recent chemotherapeutic advances up to half of all patients relapse. Here we report the results from a phase 2, single-arm, single-center trial evaluating the safety and efficacy of lenalidomide plus rituximab in elderly patients with relapsed or refractory DLBCL.Patients and MethodsBetween March and June 2009, elderly patients (65 years of age or older) with relapsed/refractory DLBCL who had been heavily pretreated were recruited. Oral lenalidomide (20 mg/d for 21 days of each 28-day cycle) was initiated for four cycles and rituximab (375 mg/m²) was administered on day 1 and day 21 of each 28-day cycle for four cycles. After this induction phase, patients achieving a complete response (CR), partial response (PR), or stable disease (SD) were given lenalidomide maintenance therapy at the same schedule for another 8 months.ResultsA total of 23 patients with a median of three prior treatments (range, 2 to 8) were included. The overall response rate (CR + PR) at the end of the induction phase was 35% (n = 8). Ten patients (7 CR, 1 PR, and 2 SD patients) were eligible for lenalidomide maintenance and 8 of these patients achieved a CR. Adverse events were manageable and the most common included neutropenia and thrombocytopenia.ConclusionOral lenalidomide in combination with rituximab is active in elderly patients with relapsed/refractory DLBCL with a high percentage of patients achieving a continuous CR after lenalidomide maintenance.     

Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma

BackgroundPixantrone is an aza-anthracenedione with enhanced, preclinical antitumor activity and reduced cardiotoxicity compared with doxorubicin.Patients and methodsWe compared the efficacy and toxic effect of CPOP-R (substituting pixantrone for doxorubicin) against CHOP-R in untreated, diffuse large B-cell lymphoma (DLBCL) patients. The primary objective was to demonstrate non-inferiority of CPOP-R by complete response/complete response unconfirmed (CR/CRu) rate.ResultsThe CR/CRu rate for CPOP-R was 75% versus 84% for CHOP-R. Three-year overall survival was lower for CPOP-R (69% versus 85%) (P = 0.029). Median progression-free survival (PFS) was not reached for CPOP-R and was 40 months for CHOP-R [HR 95% confidence interval (CI) = 1.02 (0.60, 1.76), P = 0.934]. Fewer CPOP-R patients developed congestive heart failure (CHF) (0% versus 6%, P = 0.120), ≥20% declines in ejection fraction (2% versus 17%, P = 0.004), or elevations in troponin-T (P = 0.003).ConclusionsCPOP-R is an active regimen with modestly lower response rates than CHOP-R but similar PFS and event-free survival. This study demonstrates a substantially lower cardiotoxicity of pixantrone compared with doxorubicin when used as first-line therapy in DLBCL.     

Effect of addition of rituximab to salvage chemotherapy on outcome of patients with diffuse large B-cell lymphoma relapsing after an autologous stem-cell transplantation

BackgroundWe have investigated if rituximab-based salvage regimens improve response rates and survival of patients with diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous stem-cell transplantation (ASCT).Patients and methodsWe have retrospectively analyzed 82 patients with DLBCL who received salvage therapy for relapse or progression after ASCT. Patients were divided into two groups, according to whether rituximab-based salvage regimens were given (n = 42, ‘R-’ group) or not (n = 40, ‘R+’ group) after ASCT.ResultsPatients in the R+ group had better complete remission (CR) (55% versus 21.4%, P = 0.006) and overall response (OR) (75% versus 40.4%, P = 0.001) rates, and better 3-year event-free survival (EFS) (37% versus 9%, P = 0.002) and overall survival (OS) (50% versus 20%, P = 0.005) than patients in the R- group. Patients retreated with rituximab had better CR (42.9% versus 21.4%, P = 0.032) and OR (66.7% versus 40.4%, P = 0.019) rates, and better OS (36.2% versus 20% at 3 years, P = 0.05) and EFS (36.2% versus 9% at 3 years, P = 0.05) than patients who received chemotherapy alone at relapse after ASCT.ConclusionsThe addition of rituximab to salvage chemotherapy improves response rates and EFS in patients with relapsed DLBCL after ASCT. These patients may benefit from rituximab retreatment, although larger prospective studies are needed to confirm these results.     

A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas

BackgroundEverolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results.Patients and methodsParticipants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response.ResultsThe objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL–not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia.ConclusionThe everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.     

Outcomes of Treatment for HIV-Infected Lymphoma Patients: A National Cancer Database (NCDB) Analysis

BackgroundHuman immunodeficiency virus (HIV) infection may be a predictor of undertreatment of patients with lymphoma. We hypothesized treatment with systemic therapy (SysT) or hematopoietic stem cell transplantation (HCT) in the first-line setting leads to improved outcomes and sought to compare the predictors for treatment and outcomes with non-HIV (HIV−) patients.MethodsPatients with lymphoma diagnosed between 2004 and 2015 were extracted from the National Cancer Database (NCDB). Patients were categorized as HIV+ and HIV−. First-line treatment was categorized as no systemic therapy reported (noSyst), SysT, or HCT. Multivariate analysis to predict treatment and survival was performed.ResultsWe identified 552,513 lymphoma patients, of whom 11,160 HIV+ versus 349,607 HIV− patients were eligible for analysis. Among HIV+, the positive predictors for SysT were insurance and higher income, whereas female sex and minority racial status predicted lower likelihood for SysT. Forty HIV+ patients underwent HCT. Treatment of HIV+ lymphoma patients resulted in improved outcomes: 3-year overall survival 43.6% in noSyst versus 58.1% SysT (hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.52-0.61; P < .005) versus 62.2% HCT (HR 0.42; 95% CI, 0.14-1.3; P = .08). The outcomes were lower compared to non-HIV patients (3-yr overall survival 67.3% with SysT and 62.2% HCT).ConclusionPatients with lymphoma with HIV benefit from SysT when feasible but outcomes are worse than non-HIV patients. HCT should be offered to HIV+ patients with lymphoma in the appropriate clinic setting. Individual characteristics of the patients and complications could not be evaluated in the present study but should be a focus for future research.     

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial

BackgroundThe prognosis of elderly patients with aggressive B-non-Hodgkin’s lymphoma after first lymphoma-related treatment failure (TF-L) is not well described.MethodsWe analysed patient characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial.ResultsTF-L occurred in 301 of the 1222 (24.6%) patients; 297 patients could be analysed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared with CHOP (23.0% versus 36.4% at 2 years, P = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% versus 0% at 2 years, P < 0.001) or negative MYC-IHC (41.0% versus 16.8% at 2 years, P = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (P < 0.001). The benefit of R was significant after first-line CHOP [2-year overall survival (OS) 49.6% versus 19.1%, P < 0.001] as well as after R-CHOP (2-year OS 33.1% and 22.5%, P = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen.ConclusionMYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first-line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy; however, survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.