Brentuximab vedotin as salvage treatment in Hodgkin lymphoma naïve transplant patients or failing ASCT: the real life experience of Rete Ematologica Pugliese (REP)

Brentuximab vedotin (BV) shows a high overall response rate (ORR) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) after autologous transplant (ASCT). The aim of this multicenter study, conducted in nine Hematology Departments of Rete Ematologica Pugliese, was to retrospectively evaluate the efficacy and safety of BV as salvage therapy and as bridge regimen to ASCT or allogeneic transplant (alloSCT) in R/R HL patients. Seventy patients received BV. Forty-five patients (64%) were treated with BV as bridge to transplant:16 (23%) patients as bridge to ASCT and 29 (41%) as bridge to alloSCT. Twenty-five patients (36%), not eligible for transplant, received BV as salvage treatment. The ORR was 59% (CR 26%). The ORR in transplant naïve patients was 75% (CR 31%). In patients treated with BV as bridge to alloSCT, the ORR was 62% (CR 24%). In a multivariate analysis, the ORR was lower in refractory patients (p?<?0.005). The 2y-OS was 70%. The median PFS was 17 months. Ten of the 16 (63%) naïve-transplant patients received ASCT, with 50% in CR before ASCT. In the 29 patients treated with BV as bridge to alloSCT, 28 (97%) proceeded to alloSCT with 25% in CR prior to alloSCT. The most common adverse events were peripheral neuropathy (50%), neutropenia (29%) and anemia (12%). These data suggest that BV is well tolerated and very effective in R/R HL, producing a substantial level of CR. BV may also be a key therapeutic agent to achieve good disease control before transplant, improving post- transplant outcomes, also in refractory and heavily pretreated patients, without significant overlapping toxicities with prior therapies.     

Cost-effectiveness analysis of therapeutic options for chronic hepatitis C genotype 3 infected patients

Background: This study provides a cost-effectiveness analysis of therapeutic strategies for chronic hepatitis C genotype 3 infected patients in Spain.

Methods: A Markov model was designed to simulate the progression in a cohort of patients aged 50 years over a lifetime horizon.

Results: Sofosbuvir (SOF) plus peginterferon and ribavirin for 12 weeks was a cost-effective option when compared to standard of care (SoC) in the treatment of both ‘moderate fibrosis’ and ‘cirrhotic’ patients. Incremental cost-effectiveness ratios were €35,276/QALY and €18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens versus SoC were over the threshold limit considered, at €56,178/QALY and €77,378/QALY for ‘moderate fibrosis’ and ‘cirrhotic’ patients respectively.

Conclusion: Addition of SOF to IFN-based regimens for genotype 3 was cost-effective for both ‘moderate fibrosis’ and ‘cirrhotic’ patients. IFN-free options including SOF and DCV association required price reductions lower than the list prices to be considered cost-effective.     

High-dose thiotepa,etoposide and carboplatin as conditioning regimen for autologous stem cell transplantation in patients with high-risk Hodgkin’s lymphoma

Abstract

Background: Autologous stem cell transplantation (ASCT) generally provides good results in Hodgkin’s lymphoma (HL). We studied a high-dose chemotherapy regimen based on thiotepa, etoposide and carboplatin (TECA).

Methods: Fifty-eight patients with advanced HL were treated with thiotepa, etoposide and carboplatin for transplant induction.

Results: The overall response rate was 79·3% (39 CR: 67·2%; and 7 PR: 12·1%); 12 patients (20·1%) were non-responders. The 5-year overall survival rate was 77·6%; five initially responder patients relapsed within the first 5 years of follow-up and underwent salvage therapy.

Conclusion: The TECA conditioning regimen for ASCT in HL results in a good anti-HL effect, positive response to treatment and high 5-year overall survival rate. It was also well tolerated and did not induce excessive toxicity, suggesting that TECA may be a very useful conditioning regimen for HL.     

Health literacy levels in outpatients with liver cirrhosis

Abstract

Objective: Health literacy (HL) is a concept covering a range of cognitive and social skills that comprises aspects necessary for patients to navigate in the healthcare system. Our study aimed to investigate HL in patients with liver cirrhosis and determine factors associated with low HL.

Methods: Data were collected among outpatients with cirrhosis (n?=?108), using three dimensions from the Health Literacy Questionnaire. The selected dimensions were: ‘Social support for health’ (Social support scale), ‘Ability to actively engage with healthcare providers’ (Engagement scale), and ‘Understand health information well enough to know what to do’ (Information scale). Unpaired t-test was used to investigate differences on the HLQ scale scores. The effect sizes (ES) were calculated between groups using Cohen’s d.

Results: A total of 105 patients completed the questionnaire. Mean age of respondents was 60.6 years (45.5% females). A majority had alcoholic liver cirrhosis (64.8%) and 36.2% were living alone. Males had a low level of Social support HL (p?p?Conclusions: Male outpatients with liver cirrhosis were found to have low levels of HL, so were patients with low education. In order to effectively communicate and support patients to self-manage their disease, healthcare providers can benefit from including a focus on HL in planning and delivering health care to patients with liver cirrhosis.     

Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party

Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre‐transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow‐up for survivors was 41 months. Patients in the BV group were more heavily pre‐treated (median pre‐allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre‐allograft BV had no impact on acute graft‐versus‐host disease (GVHD), non‐relapse mortality, cumulative incidence of relapse, progression‐free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0·64; 95% confidence interval = 0·45–0·92; P < 0·02). Older age, poor performance status, use of pre‐transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success.     

Third-line treatment with second-generation tyrosine kinase inhibitors (dasatinib or nilotinib) in patients with chronic myeloid leukemia after two prior TKIs: real-life data on a single center experience along with the review of the literature

Objectives: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib?→?nilotinib or imatinib?→?dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT.

Methods: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated.

Results: Out of 209 patients, third-line dasatinib/nilotinib was administered in 21. During the follow-up, 16 out of 21 patients gained and/or maintained an optimal response, and 4 patients died due to progression. Seventeen patients were alive at the time of the analysis, of which 13 were still on TKI, whereas 4 patients quit treatment.

Discussion: In patients failing two lines of TKI, dasatinib or nilotinib can be beneficial and safely administered as a third-line treatment especially in nations with restricted resources.     

Use of rituximab in diffuse large B-cell lymphoma in the salvage setting

The addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy was a milestone in the development of front-line therapy for diffuse large B-cell lymphoma (DLBCL). R-CHOP and equivalent rituximab-containing anthracycline-based regimens are now widely accepted as the standard of care in this setting. However, the optimal treatment for patients with DLBCL relapsing or progressing after front-line therapy is not yet established. This review explores the role of rituximab in the treatment of DLBCL in the salvage setting, as monotherapy, in combination with chemotherapy or novel agents, and in the context of autologous stem cell transplantation (ASCT). Current evidence suggests that rituximab may improve outcomes in several ways: the higher response rates achieved with rituximab-based induction in the salvage setting optimize the number of patients who are able to proceed to high-dose therapy -ASCT; rituximab may improve outcomes following ASCT when used as post-transplantation consolidation/maintenance therapy; and addition of rituximab to salvage regimens may improve outcomes for patients ineligible for transplantation. However, patients refractory to or relapsing after first-line therapy (including rituximab-based regimens) still have a poor prognosis. In conclusion, rituximab in salvage therapy for DLBCL is effective and well tolerated. Ongoing studies will further clarify the optimal use of rituximab in the salvage setting.     

Hematology Morphology Forum

Introduction: Thrombotic thrombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, mainly as a consequence of autoimmunity. Plasma exchange (PEx) is standard, achieving complete remission (CR) in 77–83% of cases, but rates are variable depending on ADAMTS-13 activity and relapse is frequent in patients with <10%. Thus, an effective front-line immunosuppressive treatment is needed.

Materials and methods: We administered PEx daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks to 10 patients with a first TTP episode and 1 relapsed patient (8 females (72%) and 3 males (28%)). Median age was 34 years (15–46) and laboratory parameters at diagnosis were as follows: platelets 11?×?10⁹/l (range 7–27.4?×?10⁹/l), lactate dehydrogenase 1822?U/l (range 705–8220?U/l, normal 70–180?U/l), and haemoglobin 6?g/dl (range 4.2–11.8?g/dl). ADAMTS-13 activity was determined in eight patients and was <10% in all. ADAMTS-13 autoantibody titre was determined in seven patients and was >15?units/ml in all (ref: negative <12, undetermined 12–15, positive >15?units/ml); Shiga toxin was negative in all patients. The median number of PEx until CR was 7 (range 4–12); prednisone 1?mg/kg was administered to six patients.

Results: The median follow-up was 22 months (range 4–49) and the estimated 2-year relapse-free survival was 89%; one HIV+ patient relapsed at 8 months follow-up. No complications related to PEx or rituximab were reported.

Conclusions: Our study suggests that low-dose rituximab and PEx are effective as front-line treatment for acute TTP; however, a prospective trial is needed to demonstrate whether low-dose rituximab is as effective as the conventional dose.     

Sofosbuvir,velpatasvir and voxilaprevir combination for the treatment of hepatitis C

Introduction: The advent of direct-acting antiviral (DAA) treatments for chronic hepatitis C virus (HCV) infection has dramatically increased rates of cure. However, there remain difficult-to-treat populations, including patients with genotype 3 infection and cirrhosis, and limited salvage treatment options for those that have failed first-line DAA therapy.

Areas covered: This is a review of the preclinical and clinical development of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), an interferon-free, oral, once daily, pangenotypic treatment for chronic HCV infection. All relevant literature from 2015 through June of 2017 is included.

Expert commentary: Voxilaprevir, a second-generation HCV protease inhibitor, in combination with the already approved combination of sofosbuvir and velpatasvir, was evaluated in the POLARIS trials and found to be a safe and effective regimen. Patients with prior DAA treatment failure, genotype 3, cirrhosis and/or unfavorable resistance profiles all achieved cure rates of 96% or greater. The most distinctive role for this potent regimen may prove to be as a salvage regimen for patients who have failed previous DAA therapy.     

Rituximab plus cladribine with or without cyclophosphamide in patients with relapsed or refractory chronic lymphocytic leukemia

OBJECTIVES: The aim of our study was to determine the feasibility, effectiveness and toxicity of combined regimens consisting of rituximab and cladribine (2-CdA) (RC) and RC plus cyclophosphamide (RCC) in the treatment of patients with recurrent or refractory chronic lymphocytic leukemia (CLL). METHODS: The RC regimen consisted of rituximab given on day 1 and 2-CdA (days 2-6). The RCC protocol included rituximab (day 1), 2-CdA (days 2-4) and cyclophosphamide given on days 2-4. The courses were re-administered at time intervals of 4 weeks or longer if severe myelosuppression occurred. RESULTS: Forty-six patients with CLL entered the study. Eighteen patients were treated with RC and 28 with RCC regimen. The median number of courses administered were three cycles (range 1-6). Three (6.5%) patients (95% CI: 1-14%) achieved a complete response and 31 (67%) patients (95% CI: 50-83%) a partial response. According to the particular regimen, the overall response rate was obtained in 12 (67%) patients treated with RC (95% CI: 45-89%) and in 22 patients (78%) treated with RCC (95% CI: 62-93%). The median progression free survival of responders to RC/RCC regimens was 12 months (range 4-46). Hypersensitivity to rituximab occurred in 16 (33%) patients, mostly during the first infusion of the drug. Grade 3/4 neutropenia was seen in six (13%) patients, grade 3/4 thrombocytopenia in three (9%) patients and grade 3/4 infections were observed in ten (28%) patients. CONCLUSIONS: These data indicate that both RC and RCC regimens are feasible in heavily pretreated patients with CLL, showing also distinct therapeutic activity and relatively low toxicity, even in patients previously treated with cladribine-based protocols.     

Intensive conditioning regimen of etoposide (VP-16), cyclophosphamide and carmustine (VCB) followed by autologous hematopoietic stem cell transplantation for relapsed and refractory Hodgkin's lymphoma

Several high-dose therapy regimens are used for autologous hematopoietic stem cell transplantation (auto-HSCT) for relapsed and refractory Hodgkin's lymphoma (HL) with variable disease response. An intensified regimen of etoposide (VP-16) 2,400 mg/m(2), cyclophosphamide 7,200 mg/m(2) and carmustine (BCNU) 600 mg/m(2) (VCB) pre-auto-HSCT was developed to overcome disease recurrence. A total of 43 relapsed and refractory HL patients underwent auto-HSCT between January 1992 and December 2004. At day 100 there were 37 (86%) complete responses. A total of 40 patients survived beyond day 100, 14 of whom subsequently relapsed/progressed. At a median follow-up of 4.9 years (range 1.5-11.4 years), 26 patients (60%) are alive and disease free. Five-year actuarial event-free survival (EFS) was 53% (95% CI 35-70%) and median EFS was 5.9 years. Median progression-free and overall survivals have not been reached. EFS was reduced with an increasing number of prognostic factors (Karnofsky performance status, KPS <90, chemotherapy-resistant disease and >or=3 chemotherapy regimens prior to transplant or=2; P=0.049). Grade III-IV regimen-related toxicity was 9% (n=4). The 1-year cumulative incidence of interstitial pneumonitis (IP) was 36%, however only two patients died of IP complications. Disease progression was the most common cause of death (n=10, 23%). Intensive VCB is an effective and well-tolerated preparative regimen for relapsed and refractory HL auto-HSCT.     

Efficacy and safety results from a randomized double-blind study comparing proposed biosimilar ABP 798 with rituximab reference product in subjects with moderate-to-severe rheumatoid arthritis

Background/objectives

ABP 798 is a proposed biosimilar to the originator biologic rituximab, an anti-CD20 monoclonal antibody. This comparative clinical study evaluated the pharmacokinetics (PK), safety, and efficacy of ABP 798 versus rituximab reference product (RP) in patients with moderate-to-severe rheumatoid arthritis (RA).

Methods

Adults with moderate-to-severe RA with an inadequate response or intolerance to other disease-modifying anti-rheumatic drugs including 1 or more tumor necrosis factor inhibitor therapies (n = 311) received ABP 798, US-sourced rituximab RP (rituximab US), or EU-sourced rituximab RP (rituximab EU) (1000 mg, 2 weeks apart). At week 24, ABP 798- or rituximab EU-treated subjects received a second dose of the same treatment, while rituximab US-treated subjects transitioned to receive ABP 798. The key efficacy endpoint was DAS28-CRP change from baseline at week 24. Other efficacy endpoints included DAS28-CRP at other time points; ACR20, ACR50, and ACR70 criteria; and hybrid ACR. The rituximab RP groups were pooled for all efficacy endpoints since PK equivalence had been established between rituximab US and rituximab EU.

Results

Clinical equivalence between ABP 798 and rituximab RP was established as the 90% confidence interval for DAS28-CRP change from baseline at week 24 fell within the prespecified equivalence margin (− 0.6, 0.6). Safety and immunogenicity profiles of ABP 798 were comparable across treatment groups and not affected by single transition from RP to ABP 798.

Conclusions

Clinical equivalence in terms of efficacy, safety, and immunogenicity was established between ABP 798 and rituximab RP in this comparative clinical trial in patients with moderate-to-severe RA.

Treatment patterns and outcomes among patients with high-intermediate/high-risk diffuse large B-cell lymphoma in the USA

Abstract

Objective

Clinical trials have demonstrated improved outcomes for patients with diffuse large B-cell lymphoma (DLBCL) treated with regimens containing rituximab, but variations in real-world treatment patterns and outcomes have not been studied. The objective of this study was to characterize real-world treatment patterns and outcomes in higher risk DLBCL patients.

Methods

Patients with an International Prognostic Index score (IPI) ≥3 who received initial rituximab-based therapy from 2005 to 2012 were identified via electronic medical record data from the International Oncology Network. Initial therapy, rates of complete response (CR), post-CR treatments, and outcomes were evaluated.

Results

Among 257 eligible patients, 75% achieved a CR: 77% (158/206) of patients receiving R-CHOP compared to 71% (36/51) of patients receiving initial therapies other than R-CHOP. Post-CR, 78% of the 158 patients receiving R-CHOP underwent active surveillance; 13% received maintenance rituximab-based treatment; and 6% received radiation therapy. Relapse rates among patients receiving maintenance rituximab, active surveillance, and radiation therapy were 28% (6/21), 19% (24/124), and 0%, (0/10), respectively (P = 0.08).

Discussion

This study found that active surveillance continues to be the most commonly utilized treatment regimen among DLBCL patients with an IPI score ≥3 achieving a CR on first-line R-CHOP. Other approaches aimed at increasing the time to relapse are being utilized as well, but the clinical benefit of these modalities is unclear.

Conclusion

Results of this study are consistent with the results from clinical trials and suggest the need for further evaluation of maintenance therapy options for patients at higher risk of relapse.     

High-dose cyclophosphamide, carmustine, and etoposide and autologous bone marrow transplantation for relapsed Hodgkin's disease

Thirty patients with relapsed Hodgkin's disease were treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) and autologous bone marrow transplantation. The median age of the patients was 28 years, and 18 were male. More than half had extranodal sites of relapse and constitutional symptoms. Most had been heavily pretreated with multiple salvage chemotherapy regimens and radiotherapy. At the time of transplantation, 23 patients were having progressive disease despite salvage chemotherapy. High-dose CBV chemotherapy induced complete responses in 15 patients and partial responses in 10 patients. Eleven patients are still in complete remission, 1 of whom has had an unmaintained remission for more than 44 months. Toxicity was moderate; all patients had severe myelosuppression requiring supportive therapy, and 1 patient failed to reconstitute her bone marrow. High-dose CBV chemotherapy and autologous bone marrow rescue proved to be effective as salvage therapy for a select group of heavily pretreated patients with relapsed Hodgkin's disease.     

Impact of treatment-related toxicity on outcome of HCV-positive diffuse large B-cell lymphoma in rituximab era

Novelty and Impact

This first study compares the survival of HCV-positive DLBCL treated with and without rituximab which showed in toxicity and the outcome.

Background

The effect of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era is unclear. The treatment and the outcome of patients with DLBCL and HCV infection are still a matter of debate.

Methods

We analyzed 137 DLBCL patients positive to HCV, treated with chemotherapy regimens include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab. Survival outcomes and hepatic toxicity were compared in DLBCL patients positive to HCV infection according to CHOP ± rituximab.

Result

Our result showed that the group of patients treated with R-CHOP has significant high incidence of hepatic toxicity grade (3–4) (28 vs. 18%, P value 0.001) and worse progression-free survival (55 vs. 80%, P value 0.002) in comparison with the group treated with CHOP, and also there is significant difference between both groups in overall survival. This first study compares the survival of HCV-positive DLBCL treated with and without rituximab which showed significant differences.

Conclusion

We conclude that HCV-positive patients with DLBCL treated with rituximab plus CHOP have high incidence in hepatic toxicity. Speci?c protocols evaluating antiviral therapy should be designed for these patients     

Therapy of relapsed Hodgkin lymphoma

The majority of patients who are diagnosed with Hodgkin lymphoma (HL) will be cured with primary chemotherapy. For those who relapse, autologous stem cell transplantation (ASCT) has become the standard of care. Randomized clinical trials have demonstrated that approximately 50% of patients with chemosensitive relapsed HL can achieve long term disease free survival with ASCT. However, optimal therapy of those who have chemorefractory disease or who relapse after an ASCT has not been established. Reduced intensity allogeneic stem cell transplantation may benefit these patients, although a definite graft versus HL effect has not been demonstrated and treatment-related mortality remains relatively high. New salvage regimens that incorporate gemcitabine, vinorelbine, rituximab, and/or monoclonal antibodies against CD30 are being investigated.     

Long-term safety and efficacy of rituximab in 7 Japanese patients with ANCA-associated vasculitis

Abstract

Objectives. The safety and efficacy of rituximab were examined in a multicenter open-label pilot study in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan.

Methods. Patients with refractory AAV were administered a rituximab infusion at a weekly dose of 375 mg/m² for 4 weeks. All patients also received oral daily prednisolone. The primary outcome was complete remission, which was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 or 1.

Results. The mean age of the 7 patients was 57 (range, 34–71) years. The mean follow-up period after rituximab treatment was 62.9 (range, 4.8–81) months. The mean BVAS at entry was 16.7 (range, 2–34). Complete remission occurred in all cases, except in 1 case in which the patient died, with a significant decline in BVAS from baseline at 12 months after initiation of rituximab. Rituximab reduced granulomatous orbital involvement in a patient with granulomatosis with polyangiitis. Relapse occurred in five patients. Adverse events included de novo hepatitis B in one patient, cancer (hepatocellular carcinoma and prostate cancer) in two patients, and transient visual disturbance, atypical mycobacterial infection, urinary tract infection, sepsis, and cytomegalovirus infection. Two patients died due to recurrent infections and airway obstruction, caused by an AAV lesion.

Conclusions. Rituximab had a beneficial effect on refractory AAV in Japanese patients, but several adverse effects occurred during rituximab treatment.     

Efficacy of chemotherapy or chemo‐anti‐PD‐1 combination after failed anti‐PD‐1 therapy for relapsed and refractory hodgkin lymphoma: A series from lysa centers

Anti‐PD‐1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti‐PD‐1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti‐PD‐1 therapy, assessed by PET‐CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pretreated before anti‐PD‐1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti‐PD1 therapy were progressive disease (PD) (n = 24) and partial response (PR) (n = 6). For the 24 PD patients, median anti‐PD‐1 related PFS was 7.5 months (95%CI, 5.7‐11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti‐PD‐1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow‐up of 12.1 months (7‐14.7), the median PFS following the initiation of CT was 11 months (95% CI 6.3‐not reached) and the median of overall survival was not reached. These observations in highly pretreated HL patients suggest that anti‐PD‐1 therapy might re‐sensitize tumor cells to CT.     

Treatment of Epstein Barr virus‐induced haemophagocytic lymphohistiocytosis with rituximab‐containing chemo‐immunotherapeutic regimens

Haemophagocytic lymphohistiocytosis (HLH) is a life threatening complication of Epstein–Barr virus (EBV) infection. The anti‐CD20 antibody rituximab depletes B cells, leading to improved outcomes for patients with EBV‐associated B‐lymphoproliferative disorders. To gather data on the use of rituximab in EBV‐HLH, we performed a retrospective investigation involving 42 EBV‐HLH patients who had received treatment with rituximab‐containing regimens. On average, patients received 3 rituximab infusions (range 1–10) at a median dose of 375 mg/m². In all patients, rituximab was administered with other HLH‐directed medications, including steroids, etoposide and/or ciclosporin. Rituximab‐containing regimens appeared well tolerated and improved clinical status in 43% of patients. Examination of laboratory data obtained prior to and within 2–4 weeks after the first rituximab dose revealed significant reductions in EBV load (median load pre‐rituximab: 114 200 copies/ml, median post‐rituximab: 225 copies/ml, P = 0·0001) and serum ferritin levels (median ferritin pre‐rituximab: 4260 μg/l, median post‐rituximab: 1149 μg/l, P = 0·001). Thus, when combined with conventional HLH‐directed therapies, rituximab improves symptoms, reduces viral load and diminishes inflammation. These data support the incorporation of rituximab into future prospective clinical trials for patients with EBV‐HLH.     

Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1-19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27-42) and 29% (95% CI 22-36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.