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Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell-lymphoma patient cohort from five centers in Germany and the United States (Germany, N=66; US, N=106, Total, N=172), we demonstrate that wide-spectrum antibiotics treatment (‘high-risk antibiotics’) prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely confounded by an increased pre-treatment tumor burden and systemic inflammation in high-risk antibiotics-pre-treated patients. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals impacting CAR-T efficacy, we focused on the high-risk antibiotics non-exposed patient population. Indeed, in these patients, significant correlations were uncovered between pre-CAR-T-infusion Bifidobacterium longum and microbiome-encoded peptidoglycan biosynthesis, and CAR-T treatment-associated 6-months survival or lymphoma progression. Furthermore, predictive pre-CAR-T treatment microbiome-based machine-learning algorithms trained on the high-risk antibiotics non-exposed German cohort and validated by the respective US cohort robustly segregated long-term responders from non-responders. Bacteroides, Ruminococcus, Eubacterium and Akkermansia were most important in determining CAR-T responsiveness, with Akkermansia also associating with pre-infusion peripheral T cell levels in these patients. Collectively, we uncover conserved microbiome features across clinical and geographical variations, which may enable cross-cohort microbiome-based predictions of outcomes in CAR-T cell immunotherapy.

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their Food and Drug Adminsitration approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day (30-d) major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, four exacerbations of heart failure/cardiomyopathy, four cerebrovascular accidents, three myocardial infarctions, and one patient died due to myocardial infaction. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range, 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival or with overall survival. Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited follow-up, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively (

Purpose We report the long-term results of a prospective trial conducted to determine the efficacy and safety of radiation therapy (RT) alone in treating localized mucosa-associated lymphoid tissue (MALT) lymphoma. Methods and Materials Patients with localized MALT lymphoma were eligible and treated with involved field RT to doses of 24 to 39.6 Gy. Relapse-free survival (RFS) was the primary endpoint. Kaplan-Meier analysis was used to estimate RFS, progression-free survival (PFS), and overall survival (OS) defined from time of study entry. Preplanned subgroup analyses were performed based on site of involvement. Results From 2000 to 2012, 75 patients were accrued; 73 received protocol-specified RT. Median follow-up was 9.8 years. Thirty-four patients had gastric MALT, 17 orbital, 13 head and neck nonorbit, 4 skin, and 5 disease of other sites. Thirteen of 34 patients with gastric MALT were Helicobacter pylori positive at the time of initial diagnosis and underwent 1 to 3 courses of triple antibiotic therapy. All gastric MALT patients had documented persistent MALT without H. pylori on endoscopy before enrollment in the study. All patients achieved a complete response with a median time of 3 months. Eleven patients (15%) had disease relapse, 9 of which were at sites outside the RT field with median time to progression of 38.3 months. Median PFS was 17.5 years, and median RFS and OS were not reached. The 10-year relapse-free rate was 83% (95% confidence interval [CI], 74%-93%). The 10-year PFS rate was 71% (95% CI, 60%-84%). The 10-year OS rate was 86% (95% CI, 77%-96%). RFS, PFS, and OS did not differ by disease site (P = .17, .43, and .50, respectively). All relapses were successfully salvaged. One patient developed metastatic gastric adenocarcinoma and was found to also have recurrent MALT on biopsy. Otherwise, all relapsed patients were alive without evidence of disease at last follow-up, and no patient died of MALT lymphoma. Sixty-seven patients (92%) experienced acute toxicity during radiation, all of which were grade 1 and 2, with only 1 grade 3 toxicity. Twenty-two patients (30%) experienced late toxicity, with only 1 grade 3 toxicity. Conclusions This prospective study confirms that RT for MALT lymphoma provides excellent long-term RFS with acceptable rates of toxicity. Current efforts are focused on RT de-escalation in an effort to further avoid treatment-related morbidity. Clinicaltrials.gov NCT04465162 .

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity, with limited data on the outcome in the relapsed/refractory setting. We evaluated the outcome of all patients diagnosed between 04/1979 and 01/2019 with relapsed or progressive NLPHL after initial active therapy at two institutions, refractory disease being defined as lack of response to treatment and/or relapse within three months of treatment. NLPHL patients with histological evidence of transformation at time of first relapse or progression were excluded. In total, 69 patients with recurrent NLPHL were included in the study. After a median follow-up after initial diagnosis of 14 years (range, 0·5-46 years), median progression-free survival after front-line treatment (PFS-1) was four years. Second-line therapy included chemotherapy in 28 (41%) patients, biological therapy (rituximab, lenalidomide or brentuximab vedotin) in 14 (20%), high-dose chemotherapy followed by autologous stem cell transplant in 14 (20%) and radiation therapy (RT) alone in 10 (15%). The five-year PFS after second-line therapy (PFS-2) was 68% [95% confidence interval (CI), 54-79%] but the five-year overall survival (OS) after second-line therapy (OS-2) remained excellent, at 94% (95% CI, 85-99%). Due to excellent outcome in case of recurrence, studies aimed at characterizing its biology to guide therapy de-escalation are needed.

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (D...

Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P = .03) and C-reactive protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin Lymphoma (NHL) that can be further classified into 3 sub-types: nodal, extra-nodal and splenic [1]. MZL rarely involves the central ne...

Classical Hodgkin lymphoma (HL) patients achieve excellent outcomes; therefore, treatment de-escalation strategies to spare toxicity have been prioritized. In a large randomized trial of early stage HL patients, omission of chemotherapeutic agents including bleomycin from the standard ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen was not found to be non-inferior; however the effect of partial omission is unknown. We investigated the effect of bleomycin omission on outcome for 150 early stage HL patients. At eight years, freedom from relapse was 99% for both patients who received complete or incomplete bleomycin, which is reassuring for patients requiring bleomycin omission due to toxicity.

In 2 randomized phase 3 trials BR resulted in longer progression-free survival (PFS) than frontline R-CHOP in patients with indolent and mantle cell lymphoma. However, in subset analyses of follicu...

Conditioning chemotherapy (CCT) has been shown to be essential for optimal efficacy of chimeric antigen receptor (CAR) T-cell therapy. Here, we determined whether the change in absolute lymphocyte count, referred to as delta lymphocyte index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT and whether it associated with germline genetic variants in patients with large B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 0.5 × 10(9)/L (range, 0.01–2.75 X 10(9)/L) and was significantly higher in patients who achieved complete response (p=0.04). On multivariate analysis, low DLIx was associated only with use of bridging therapy (odds ratio 0.4, 95% CI 0.2–0.8, p=0.007). Low DLIx was independently associated with shorter progression-free (p=0.02) and overall survival (p=0.02). DLIx was associated with genetic variations related to drug metabolism and macrophage biology such as ABCB1, MISP and CPVL. The impact of CCT on lymphocyte count is affected by use of bridging therapy but change in lymphocyte count is independently associated with efficacy. Studies aimed at investigating macrophage biology in this setting may suggest strategies to increase the efficacy of CCT and improve outcomes.

About 70% of patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel) and who achieve a partial response (PR) or stable disease (SD) on the day 30 (D30) positron emission tomography (PET)–computed tomography (CT) scan progress; however, the factors that are predictive of progression are unknown. This a retrospective study of patients with LBCL who were treated with axi-cel at MD Anderson Cancer Center between January of 2018 and February of 2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to a complete response (CR). Among 95 patients with a D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day −5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (P = .05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was a lower maximum standardized uptake volume (SUVmax; P < .001); all patients with D30 SUVmax ≥ 10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed between patients who converted from D30 PR/SD to subsequent CR and those who had been in CR since D30 (P = .19). Novel predictive and prognostic markers based on tissue biopsy and noninvasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 (p = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments.

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 – 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with MYC translocations without BCL2 or BCL6 rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure.

Corticosteroids are used to treat the acute complications of chimeric antigen receptor (CAR) T-cell therapy. Strati et al examine the impact of corticosteroids on patient outcomes following CAR T-cell therapy for large B-cell lymphoma. Use of higher doses of steroids is associated with shorter progression-free survival at 10 months and decreased overall survival., Key Points Higher cumulative dose of corticosteroids is associated with early progression after CAR-T therapy in large B-cell lymphoma.Higher cumulative dose and prolonged, early corticosteroid use is associated with shorter overall survival after CAR-T therapy., Visual Abstract, Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy–associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy–associated toxicities.

Key Points Question What are the radiation doses to normal tissues for patients with favorable Hodgkin lymphoma treated with modern involved-site radiation therapy? Findings This case series study included 42 patients with early-stage favorable Hodgkin lymphoma who were treated with combined modality therapy. The mean heart dose was less than 5 Gy in all patients, and the mean breast dose was 1 Gy or less in all 18 women. Meaning In this study, combined modality therapy for favorable Hodgkin lymphoma with contemporary radiation therapy delivered low radiation doses to organs at risk., This case series study investigates the radiation doses delivered to organs at risk with modern involved-site radiation therapy among patients with early-stage favorable Hodgkin lymphoma treated with 20 Gy after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)., Importance Response-adapted randomized trials have used positron emission tomography–computed tomography to attempt to identify patients with early-stage favorable Hodgkin lymphoma (ESFHL) who could be treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiation therapy (RT). While maximal efficacy is demonstrated with combined modality therapy, RT is often omitted in fear of late adverse effects; however, the application of modern RT could limit these toxic effects. Objective To determine the radiation doses delivered to organs at risk with modern involved-site RT among patients with ESFHL treated with 20 Gy after 2 cycles of ABVD. Design, Setting, and Participants This case series included 42 adult patients with ESFHL (according to the German Hodgkin Study Group criteria) who were treated between 2010 and 2019, achieved complete response by positron emission tomography–computed tomography (1-3 on 5-point scale) following 2 cycles of ABVD, and then received consolidative RT. The study was conducted at a single comprehensive cancer center. Exposures 2 cycles of chemotherapy followed by 20-Gy involved-site RT. Main Outcomes and Measures The medical records of patients with ESFHL were examined. Organs at risk were contoured, and doses were calculated. Progression-free survival, defined from date of diagnosis to disease progression, relapse, or death, and overall survival were estimated using the Kaplan-Meier method. Results The cohort comprised 42 patients with ESFHL (median [range] age at diagnosis, 35 [18-74] years; 18 [43%] women; 24 [57%] with stage II disease). At a median follow-up of 44.6 (95% CI, 27.6-61.6) months, the 3-year progression-free survival and overall survival rates were 91.2% (95% CI, 74.9%-97.1%) and 97.0% (95% CI, 80.4%-99.6%), respectively. The mean heart dose was less than 5 Gy (mean, 0.8 Gy; SD, 1.5 Gy; range, 0-4.8 Gy) in all patients. The mean (SD) breast dose for both breasts was 0.1 (0.2) Gy (left breast range, 0-1.0 Gy; right breast range, 0-0.9 Gy). Conclusions and Relevance In this study, combined modality therapy with 2 cycles of ABVD and 20 Gy for ESFHL was highly effective and avoided excess doses to organs at risk, which may limit long-term toxic effects.

In recent years, cancer treatment has evolved, and new therapies have been introduced with significant improvement in prognosis. The immunotherapies stand out owing to their efficacy and remission rate. Chimeric antigen receptor (CAR) T-cell therapy is a part of this new era of therapies. Chimeric antigen receptor T-cell therapy is a form of adoptive cellular therapy that uses a genetically encoded CAR in modified human T cells to target specific tumor antigens in a nonconventional, non-major histocompatibility complex (MHC) protein presentation. Chimeric antigen receptor T-cell therapy successfully identifies tumor antigens and through activation of T cells destroys tumoral cells. It has been found to efficiently induce remission in patients who have been previously treated for B-cell malignancies and have persistent disease. As the use of this novel therapy increases, its potential side effects also have become more evident, including major complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokine release syndrome is a major systemic inflammatory process as a result of massive cytokine production by the proliferating and activated CAR T cells in which multiple interleukins and immune cells contribute to the inflammatory response. Cytokine release syndrome has been associated with cardiovascular life-threatening complications including hypotension, shock, tachycardia, arrhythmias, left ventricular dysfunction, heart failure, and cardiovascular death. Arrhythmias, among its major complications, vary from asymptomatic prolonged corrected QT interval (QTc) to supraventricular tachycardia, atrial fibrillation, flutter, and ventricular arrhythmias like Torsade de pointes. This article focuses on the cardiovascular complications and arrhythmias associated with CRS and CAR T-cell therapy.

The impact of bridging therapy (BT) administered between leukapheresis and chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is unclear. We evaluated the influence of BT (systemic therapy [ST], radiation therapy [RT], or combined-modality therapy [CMT]) on outcomes of 148 LBCL patients who underwent leukapheresis for planned axicabtagene ciloleucel (axi-cel) infusion. The 55% (n = 81) of patients who received BT were more likely to have international prognostic index (IPI) score ≥3 (P ≤ .01), bulky disease (P = .01), and elevated lactate dehydrogenase (LDH; P ≤ .01). The 1-year progression-free (PFS) and overall survival (OS) rates were 40% and 65% in non-BT patients vs 21% and 48% in BT patients (P = .01 and .05, respectively). Twenty-four patients (16%) did not receive axi-cel, most commonly because of lymphoma progression (88%), despite 80% (n = 19) receiving BT. Among 124 patients who received axi-cel, 50% (n = 62) received BT with ST (n = 45), RT (n = 11), or CMT (n = 6); 1-year PFS and OS rates were not significantly different between BT and non-BT cohorts (P = .06 and .21, respectively). There was no difference in proportion of patients with IPI ≥3, limited-stage disease, or elevated LDH between ST, RT, and CMT groups. Compared with non-BT patients, 1-year PFS was inferior for ST-bridged patients (P = .01). RT-bridged patients had improved PFS compared with ST-bridged patients (P = .05). Despite the poor prognosis associated with requiring BT, RT can be an effective bridging strategy. Future studies are necessary to identify strategies that may improve access to CAR T-cell therapy and outcomes.

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL., Mantle cell lymphoma can be refractory to treatment. Here, the authors used single cell sequencing to study the tumours of patients that were responsive and resistant to treatment and find gains of 17q in resistant tumours, which they attribute to increased expression of Birc5 and validate these findings in mouse models of the disease.

In 2 randomized phase 3 trials BR resulted in longer progression-free survival (PFS) than frontline R-CHOP in patients with indolent and mantle cell lymphoma. However, in subset analyses of follicular lymphoma (FL), the results were incongruent. We conducted a retrospective matched-pair analysis to compare the outcome of patients with advanced stage FL, receiving frontline BR (

Neurofibromatosis Type 1 (NF1) is a genetic disorder with an incidence of 1 in 2600 to 3000 individuals. It is a clinical diagnosis characterized by cafe-au-lait macules, neurofibromas, and axillary and/or groin freckling. Because of genetic mutations in the NF1 gene affecting the Ras/mitogen-activated protein kinase pathway, there is also risk of associated soft tissue sarcomas and hematologic malignancies. However, reports of classic Hodgkin lymphoma in patients with NF1 are sparse. We report an adolescent with NF1 who developed classic Hodgkin lymphoma. Although there is an unclear association between mutations in the NF1 gene and classic Hodgkin lymphoma, further studies are warranted.

Marginal zone lymphoma of the central nervous system (CNS MZL) is rare. The clinical features, treatment, and prognosis are not well characterized. We performed a multicenter retrospective study of CNS MZL. Twenty‐six patients were identified: half with primary and half with secondary CNS involvement. The median age was 59 years (range 26‐78), 62% female and 79% with ECOG performance status ≤ 1. The most common disease site was the dura (50%). Treatment was determined by the treating physician and varied substantially. After a median follow up of 1.9 years, the estimated 2‐year progression‐free (PFS) and overall survival (OS) rates were 59% and 80%, respectively. Secondary CNS MZL was associated with 2‐year OS of 58%. CNS MZL is rare, but relative to other forms of CNS lymphoma, outcomes appear favorable, particularly among the subset of patients with dural presentation and primary CNS presentation., Marginal zone lymphoma of the central nervous system (CNS MZL) is rare. In this multicenter retrospective study of 26 patients, the estimated 2‐year overall survival rate was 80%. Outcomes appear favorable, particularly among the subset of patients with primary dural presentation.

Multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) are plasma cell disorders often treated with proteasome inhibitors. Recently, several studies evaluated carfilzomib as an initial treatment for these diseases and reported outstanding clinical outcomes. We conducted a retrospective study to report the efficacy and safety of frontline carfilzomib-based combinations in a standard of care setting. From 2014 until 2016 we identified newly diagnosed MM (n = 54) and WM (n = 6) patients treated with carfilzomib as initial therapy who met study inclusion criteria. The response rate for myeloma patients was 98% with 77% of patients undergoing upfront autologous stem cell transplant. The clinical benefit for WM was 100% with all patients having a resolution of B symptoms and anemia after treatment. Carfilzomib-based regimens are well tolerated and offer a neuropathy sparing approach with excellent responses both in newly diagnosed MM and WM making them a good choice for the frontline treatment of these diseases.