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"Double-hit" and "double-expressor" lymphomas represent distinct but overlapping subsets of aggressive B-cell non-Hodgkin lymphoma. The high rates of bone marrow involvement by these lymphomas pose a major therapeutic challenge due to the chemotherapy-resistant nature of the bone marrow microenvironment and the limited utility of rituximab-based salvage regimens in patients with relapsed/refractory disease. Preclinical studies utilizing high-dose cyclophosphamide in combination with the anti-CD52 monoclonal antibody alemtuzumab have recently shown promise in the treatment of intramedullary disease, and a Phase I human trial is now underway. In support of such efforts, here we perform CD52 target validation on a series of double-hit (n = 40) and double-expressor (n = 58) lymphomas using immunohistochemistry. CD52 expression levels varied considerably across samples, however positive staining was observed in 75% of both double-hit and double-expressor lymphomas. Similarly, high levels of CD52 expression were seen in patients whose disease was associated with high-risk clinical features, including primary refractory status (73%), higher IPI score (76%), and bone marrow involvement (74%). CD52 expression was not significantly correlated with diagnostically relevant pathologic features such as morphology, cytogenetic findings or other immunophenotypic features, but was notably present in all cases lacking CD20 expression (n = 6). We propose that CD52 expression status be evaluated on a case-by-case basis to guide eligibility for clinical trial enrollment. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) is standard of care for patients with Hodgkin lymphoma (HL) who have relapsed/refractory disease after frontline chemotherapy. Achievement of complete remission (CR) with pre-ASCT salvage chemotherapy predicts favorable outcomes post-ASCT. This phase 1/2 study evaluated the combination of brentuximab vedotin (BV) plus bendamustine as a first salvage regimen in relapsed/refractory HL. A total of 55 patients (28 primary refractory and 27 relapsed) were enrolled. Patients received BV (1.8 mg/kg) on day 1 and bendamustine (90 mg/m²) on days 1 and 2 of a 21-day cycle for up to 6 cycles. Patients could undergo ASCT any time after cycle 2. Following ASCT or completion of combination therapy if not proceeding to ASCT, patients could receive BV monotherapy for up to 16 cycles of total therapy. After a median of 2 cycles of combination therapy (range, 1-6), the objective response rate among 53 efficacy-evaluable patients was 92.5%, with 39 patients (73.6%) achieving CR. Forty patients underwent ASCT. Thirty-one patients (25 of whom underwent ASCT) received BV monotherapy (median, 10 cycles; range, 1-14). After a median of 20.9 months of follow-up, the estimated 2-year progression-free survival was 69.8% and 62.6% for patients who received ASCT and all patients, respectively. Thirty-one patients (56.4%) experienced infusion-related reactions (IRRs), with a majority occurring during cycle 2 of combination therapy. A protocol amendment requiring premedication reduced IRR severity. BV plus bendamustine as first salvage therapy in relapsed/refractory HL is highly active with a manageable toxicity profile. This trial was registered at www.clinicaltrials.gov as #NCT01874054. [ABSTRACT FROM AUTHOR]

Abstract: Background: High‐dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high‐risk lymphoma. However, elderly patients are often not considered ASCT candidates based on age alone. Subjects, Materials, and Methods: A retrospective analysis of patients ≥70 years of age with a diagnosis of Hodgkin or non‐Hodgkin lymphoma receiving ASCT between 2000 and 2016 at two partner institutions was performed. Clinical data were extracted from institutional databases and individual medical records. Multivariate analysis was performed to examine the association of clinical variables with transplant outcomes. Results: One hundred seven patients were identified. Median age at transplant was 72 years (range, 70–79). The most common lymphoma subtype was diffuse large B‐cell (n = 63, 59%). Median time to neutrophil and platelet engraftment were 10 and 12 days, respectively. With a median follow‐up for survivors of 20 months following ASCT (range, 6 months to 13.1 years), estimates for 2‐year progression‐free survival and overall survival were 58% (95% confidence interval [CI], 48%–67%) and 65% (95% CI, 55%–74%), respectively. Two‐year estimate for relapse was 34% (95% CI, 25%–44%) and nonrelapse mortality (NRM) was 7% (95% CI, 3%–14%). Multivariate analysis showed that more recent date of transplant was associated with lower NRM. The Hematopoietic Cell Transplantation‐Comorbidity Index score was not predictive of NRM in this data set (high‐risk vs. low‐risk, hazard ratio 3.45, p = .065). Conclusion: Eligibility for ASCT should be an individualized decision, and age should not be an absolute contraindication to ASCT in healthy elderly patients with lymphoma. Implications for Practice: Although high‐dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high‐risk lymphoma, elderly patients are often not considered candidates due to concern for excess toxicity and mortality. This retrospective study showed favorable transplant outcomes, including survival and toxicity, in a large cohort of lymphoma patients over 70 years of age who underwent ASCT. Eligibility for ASCT should be an individualized decision, and age should not be an absolute contraindication to ASCT in healthy elderly patients with lymphoma. [ABSTRACT FROM AUTHOR]

Background: Little is known about factors that influence hospice use for patients with blood cancers. We aimed to characterize hospice enrollment in a large population of patients with B-cell non-Hodgkin lymphoma (NHL) and assess the impact of disease characteristics such as aggressiveness and curability.Methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients age 65 years and older who were diagnosed with indolent NHL, aggressive NHL, or mantle cell lymphoma (MCL, which is aggressive and incurable) and died between 1999 and 2009. We determined the prevalence of hospice use and predictors thereof, using multivariable logistic regression. All statistical tests were two-sided.Results: Of 18 777 patients, 9645 had indolent NHL, 8226 had aggressive NHL, and 906 had MCL. Of the total cohort, 41.6% enrolled in hospice, and 34.3% enrolled three or more days before death. Compared with patients with indolent NHL, those with MCL were more likely to enroll (adjusted odds ratio [AOR] = 1.72, 95% confidence interval [CI] = 1.49 to 1.98), followed by patients with aggressive NHL (AOR = 1.41, 95% CI = 1.32 to 1.50). Other factors statistically significantly associated with hospice use included older age, female sex, white race, high socioeconomic status, and later year of death.Conclusions: In this large cohort of patients with lymphoma, hospice use was substantially lower than the national average for all cancers, suggesting either the need for improvement in enrollment or that the current hospice model is not meeting this population's end-of-life needs. Moreover, the fact that patients with MCL were most likely to enroll suggests that the end-of-life phase may be more easily determined in the context of cancers that are both aggressive and incurable. [ABSTRACT FROM AUTHOR]

BACKGROUND High-dose thiotepa, busulfan, and cyclophosphamide (TBC) with autologous stem cell transplantation (ASCT) has been used in patients with central nervous system (CNS) involvement by non-Hodgkin lymphoma (NHL). Despite limited penetration into the CNS, rituximab is active in primary CNS NHL. Therefore, high-dose rituximab was combined with TBC for ASCT in patients with CNS NHL. METHODS A single-arm phase 2 trial using high-dose rituximab with cytarabine for stem cell mobilization followed by high-dose rituximab combined with thiotepa, busulfan, and cyclophosphamide (R-TBC) for ASCT was conducted. Doses of rituximab at 1000 mg/m2 were given on days 1 and 8 of mobilization and on days −9 and −2 of TBC. The primary endpoint was efficacy. RESULTS Thirty patients were enrolled. Eighteen patients had primary CNS NHL (12 with complete remission (CR)/first partial remission (PR1) and 6 with CR/PR2), and 12 patients had secondary CNS lymphoma (5 with CR/PR1 and 7 with CR/PR2 or beyond). All patients were in partial or complete remission. Twenty-nine patients proceeded to R-TBC ASCT. Two patients developed significant neurotoxicity. The 100-day nonrelapse mortality rate was 0%, and 1 patient died because of nonrelapse causes 5 months after ASCT. For all patients, at a median follow-up of 24 months (range, 12-40 months), the estimated 2-year progression-free survival rate was 81% (95% confidence interval, 59%-92%), and the 2-year overall survival rate was 93% (95% confidence interval, 76%-98%). There were no relapses or deaths among the 18 patients with primary CNS lymphoma. CONCLUSIONS For patients with CNS involvement by B-cell NHL and especially for patients with primary CNS NHL, R-TBC ASCT shows encouraging activity and merits further study. Cancer 2015;121:226-33. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Histological transformation (HT) is a major cause of morbidity and mortality in patients with indolent non-Hodgkin lymphoma (NHL). The multicentre National Cancer Comprehensive Network database for NHL provides a unique opportunity to investigate the natural history of HT in the rituximab era. 118 patients with biopsy-confirmed indolent lymphoma and subsequent biopsy-confirmed HT were identified. Treatments for HT included autologous stem-cell transplant (auto-SCT) (n = 50), allogeneic SCT (allo-SCT) (n = 18), and treatment without transplant (n = 50). The 2-year overall survival (OS) for the entire cohort was 68%. For auto-SCT patients aged ≼60 years (n = 24), the 2-year OS was 74%. For non-transplanted patients aged ≼60 years (n = 19), the 2-year OS was 59%. The 2-year OS of patients naïve to chemotherapy prior to HT was superior to patients who were exposed to chemotherapy prior to HT (100% vs. 35%, P = 0.03). In this largest prospective cohort of patients of strictly defined HT in the rituximab era, the natural history of HT appears more favourable than historical studies. Younger patients who were not exposed to chemotherapy prior to HT experienced a prolonged survival even without transplantation. This study serves as a benchmark for future trials of novel approaches for HT in the Rituximab era. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stem cell transplant (SCT)-related outcomes and prognostication for relapsed/refractory follicular lymphoma (FL) are not well-defined in the post-rituximab era. METHODS: Through the National Comprehensive Cancer Network (NCCN) lymphoma outcomes study, 184 patients with relapsed/refractory FL who underwent autologous SCT (autoSCT) or allogenic SCT (alloSCT) fol-lowing disease relapse after prior rituximab-based therapy were examined. RESULTS: Patients who underwent autoSCT (N = 136) were older compared with patients who underwent alloSCT (N = 48) (54 versus 51 years, respectively, P = .01) and more frequently had grade 3 FL (35% versus 8%, respectively, P = .006). Patients who underwent alloSCT received more prior therapies (4 versus 3, respectively, P<.0001) and more often had resistant disease at SCT (19% versus 6%, respectively, P = .008). Cumulative 100-day non-relapse mortality (NRM) for autoSCT and alloSCT were 1% and 6%, respectively (Pc.0001), whereas 3-year NRM rates were 3% versus 24%, respectively (P<,0001). For autoSCT and alloSCT, cumulative rates of relapse, progression, and/or transformation were 32% ver-sus 16%, respectively (P = .03), whereas 3-year overall survival rates were 87% versus 61% (Pc.0001); there were no differences in failure-free survival. AlloSCT was associated with increased risk of death on multivariate analysis (hazard ratio = 2.77, 95% confidence interval =1.46-5.26, P = .002). This finding persisted on propensity scoring/matching. Multivariate analysis for autoSCT patients identi-fied age >60 years and >3 prior therapies as adverse factors. Furthermore, a survival model was created for the autoSCT cohort based on number of factors present (0,1, 2); 3-year failure-free survival was 72%, 47%, and 20%, respectively (P = .0003), and 3-year overall survival was 96%, 82%, and 62%, respectively (P<.0001). CONCLUSIONS: AutoSCT remains an effective therapy for patients with FL. For alloSCT, continued strategies to reduce NRM are needed. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and 3-deoxy-3[18F]f luorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respec tively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUVmax), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1 + months), with 1 complete and 2 partial responses (18% objective response rate 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≤ 87.5% reductions in summed FLT SUVmax and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. [ABSTRACT FROM AUTHOR]

Background: Early interim positron emission tomography (PET) scans appear powerfully predictive of outcome in Hodgkin’s lymphoma (HL), particularly in advanced-stage disease where it has been predominantly studied. The prognostic value of interim PET in limited-stage patients with nonbulky disease has not been well established.Patients and methods: Ninety-six patients with nonbulky limited-stage HL were identified who had interim and end-of-treatment PET scans. Response rate, overall survival (OS), and progression-free survival (PFS) were calculated.Results: Four-year PFS and OS for the entire cohort were 88% and 97%, respectively. Interim PET did not predict outcome, with PFS in positive and negative patients 87% versus 91% (P = 0.57), respectively. End-of-treatment PET result was predictive of outcome, with PFS of 94% in end PET-negative patients versus 54% in end PET-positive patients (P < 0.0001). Four-year OS was 100% in end PET-negative patients and 84% in end PET-positive patients (P < 0.0001).Conclusions: Interim PET scans were not predictive of outcome, compared with scans carried out at completion of therapy. End-of-treatment PET was highly predictive of PFS and OS, regardless of interim PET result. In this low-risk patient population, even patients with interim positive PET scans show a favorable prognosis. [ABSTRACT FROM PUBLISHER]