Chemoimmunotherapy In Patients Research Articles

BTK Inhibitors for the Treatment of Chronic Lymphocytic Leukemia

BTK Inhibitors for the Treatment of Chronic Lymphocytic Leukemia

Comparison of Time to Next Treatment, Health Care Resource Utilization, and Costs in Patients with Chronic Lymphocytic Leukemia Initiated on Front-line Ibrutinib or Chemoimmunotherapy

BackgroundStudies assessing ibrutinib’s economic burden versus chemoimmunotherapy (CIT) focused on pharmacy costs but not medical costs. This study compared time to next treatment (TTNT), health care resource utilization (HRU), and total direct costs among patients with chronic lymphocytic leukemia (CLL) initiating front-line ibrutinib single agent (Ibr) or CIT. Materials and MethodsOptum Clinformatics Extended DataMart De-Identified Databases were used to identify adults with ≥ 2 claims with a CLL diagnosis initiating front-line Ibr or CIT from February 12, 2014 to June 30, 2017. Inverse probability of treatment weighting was used to control for potential differences in baseline characteristics between the Ibr and CIT cohorts. Two periods were considered: entire front-line therapy (until initiation of second-line therapy) and first 6 months of front-line therapy. Comparisons with a subgroup of CIT patients initiating bendamustine/rituximab (BR) were also conducted. ResultsTTNT was significantly longer for Ibr (N = 322) relative to CIT (N = 839; hazard ratio, 0.54; P = .0163; Kaplan-Meier rates [24 months]: Ibr = 88.6%, CIT = 75.9%) and the subset of CIT patients treated with BR (N = 455; hazard ratio, 0.54; P = .0208; Kaplan-Meier rates [24 months]: Ibr = 89.0%, BR = 79.0%). During the entire front-line therapy, Ibr patients had significantly fewer monthly days with outpatient visits (rate ratio = 0.75; P = .0200). Ibrutinib’s higher pharmacy costs (mean monthly cost difference [MMCD] = $6,849; P < .0001) were offset by lower medical costs (MMCD = −$10,615; P < .0001), yielding net savings (MMCD = −$3,766; P < .0001) versus CIT. Ibr was associated with net savings (MMCD = −$5,569; P < .0001) versus BR. Cost savings and reductions in HRU were more pronounced during the first 6 months of front-line therapy. ConclusionDuring front-line CLL treatment, Ibr was associated with longer TTNT, fewer monthly days with outpatient visits, and net monthly total cost reduction versus CIT and BR.

Perioperative Chemotherapy vs Immunotherapy vs. Chemo-immunotherapy in Patients With Advanced GC and AEG

Perioperative Chemotherapy vs Immunotherapy vs. Chemo-immunotherapy in Patients With Advanced GC and AEG

PF312 RESPONSES TO R-CHOP CHEMOTHERAPY INCORPORATING BIOSIMILAR RITUXIMAB (TRUXIMA®) FOR THE FIRST LINE TREATMENT OF DIFFUSE LARGE B-CELL LYMPHOMA – INITIAL EXPERIENCE AT UNIVERSITY COLLEGE LONDON HOSPITAL

Background: In April 2017 the first biosimilar rituximab (Truxima®; NAPP) was approved in the UK for all indications of the reference biologic (MabThera®; Roche). The adoption of biosimilars is expected to deliver significant cost savings in the treatment of many conditions. The approval of Truxima® was based on comprehensive analytical and pre-clinical testing together with confirmatory clinical trials in advanced follicular lymphoma and rheumatoid arthritis with subsequent extrapolation to all licensed indications of MabThera®. There is an absence of clinical trial data supporting the use of biosimilar rituximab in other haematological malignancies, including diffuse large B-cell lymphoma (DLBCL) where the standard of care is R-CHOP chemo-immunotherapy. In the clinical trial leading to the approval of MabThera® for this indication the complete response rate at the end of treatment was 76% in patients who received R-CHOP compared to 62% in the group who received CHOP alone1. Aims: To assess the response to treatment for all patients treated for de novo stage II-IV DLBCL with R-CHOP chemo-immunotherapy including biosimilar rituximab (Truxima®). Methods: All patients starting treatment with R-CHOP for de novo stage II-IV DLBCL were identified from the electronic chemotherapy prescribing system and the following data collected: baseline demographics, performance status, staging, Revised International Prognostic Index (R-IPI), brand of rituximab received, number of R-CHOP cycles received, number of rituximab doses received, CNS prophylaxis received and response to therapy as assessed by end of treatment PET scan. Results: A total of 70 patients have completed treatment with R-CHOP chemo-immunotherapy incorporating biosimilar rituximab (Truxima®). Patients received a median of 6 cycles of CHOP (range: 1–6) and 6 doses of rituximab (range: 2–8). 58 patients completed treatment exclusively with Truxima®. 12 patients switched from MabThera® to Truxima® during their treatment after a median of 3 doses (range: 1–6). Response rates for the whole cohort of patients were as follows: Complete Response (CR): 51/70 (73%), Partial Response (PR): 11/70 (16%), Progressive Disease (PD): 6/70 (9%). Two patients died before response could be assessed. 4/70 (6%) patients switched from R-CHOP to R-GCVP chemo-immunotherapy after a median of 2 cycles (range: 1–5); all four patients achieved a CR.Summary/Conclusion: In our single-centre experience the use of biosimilar rituximab (Truxima®) does not appear to adversely impact the response rate to R-CHOP chemo-immunotherapy in patients with stage II-IV diffuse large B-cell lymphoma as assessed by post-treatment PET scan. Longer term follow-up in a larger patient group is required to confirm these results.

Comparison of Costs and Health Care Resource Utilization (HRU) in Chronic Lymphocytic Leukemia (CLL) Patients Treated with Venetoclax (VEN) or Chemotherapy (CT)/Chemoimmunotherapy (CIT)

▪BACKGROUNDMost CLL patients in the US are treated with chemoimmunotherapy (CIT) or ibrutinib; rarely do patients receive chemotherapy (CT) alone. VEN is approved for relapse/refractory (R/R) CLL patients who received one prior therapy. While treatment selection is based on risk stratification, comorbidities, patient choice, and physician preference, the economic impact of selecting VEN versus CT/CIT in R/R CLL is unknown and in the absence of prospective comparative studies, could play a role in decision-making. We aimed to compare real-world HRU of VEN versus CT/CIT-treated CLL patients receiving therapy in the second line setting.PATIENTS and METHODSCLL patients initiating second line therapy (2L) between 01/01/2016-03/31/2018 were selected from the Symphony Health's Integrated Dataverse (IDV) dataset. HRU for patients receiving VEN or CT/CIT regimens were compared from the start of the first cycle of 2L and for 3 months after treatment and reported as per-patient per-month (PPPM). Patients were ≥18 years at diagnosis and were required to have treatment after CLL diagnosis. HRU was reported for the inpatient (inpt), emergency room (ER), physician office visit (OV) or other outpatient ambulatory visits (Outpt) settings. Time to initiation was assessed from CLL diagnosis to the start of the second line of therapy. P-values were generated using chi-square tests for categorical variables and Wilcoxon test for means, as utilization and cost outcomes are often non-normally distributed.RESULTSAmong the 385 CLL patients considered in this study, 154 were treated with VEN [median age 64 years (range: 21-79)], 121 were treated with CT (median age 70 years, min 19 and max 79) and 110 were treated with CIT [median age 65 years, (range: 33-78)]. CIT in this setting were only FCR (25 patients) or BR (85 patients). There were no significant differences in gender distribution between cohorts, but higher percentage of VEN-treated patients were on Medicare/Medicaid compared to CIT patients [61% vs 52% (CIT)]. Median follow-up from initiation of 2L was significantly shorter for VEN patients when compared to CT or CIT patients (7.7 months vs 16.2 and 18.6, p-value <0.0001); likely due to later uptake in prescribing VEN relative to study period initiation. Median time from CLL diagnosis to the initiation of 2L therapy was significantly longer for VEN patients when compared to CT/CIT patients (17.3 vs 11.3 and 10.5, p-value < 0.0001).VEN inpt costs were significantly lower than CT costs ($1,615.48 vs $2,592.52, p-value <0.05) however there were no statistically significant differences observed for inpt costs between the VEN and CIT. The costs of ER visits were significantly lower for CT and CIT patients when compared to VEN ($321.48 vs $147.52 and $181.03, p<0.0001). The cost of office visits was also significantly lower for CT/CIT patients when compared to VEN ($1,971.39 vs $807.96 and $776.10, p<0.0001). Outpt visit costs were higher for CT/CIT patients when compared to VEN ($1,437.12 vs $5,163.91 and $4,824.44, p<0.0001). The total cost of medical care was significantly higher in both the CT and CIT groups when compared to VEN ($6,075.81 and $5,514.52 vs $2,439.52, p-value <0.0001); (Table).CONCLUSIONS: In R/R CLL patients, total costs of care were significantly lower in VEN patients compared to CT or CIT patients potentially implying cost-effectiveness (considering equal efficacy/toxicity). This analysis may inform shared decision-making when deciding on second line therapy especially in a value-based care environment. DisclosuresNabhan:Cardinal Health: Employment, Equity Ownership. Mato:Medscape: Honoraria; Regeneron: Research Funding; Portola: Research Funding; AstraZeneca: Consultancy; Acerta: Research Funding; Celgene: Consultancy; Prime Oncology: Honoraria; Johnson & Johnson: Consultancy; TG Therapeutics: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Research Funding. Kish:Cardinal Health: Employment. Nero:Cardinal Health: Employment.

Front-Line Ibrutinib Treatment Is Associated with Longer Time to Next Treatment, Net Total Cost Reduction, and Lower Healthcare Resource Utilization Compared to Chemoimmunotherapy in Patients with Chronic Lymphocytic Leukemia

Introduction: Novel targeted therapies greatly improved outcomes of patients with chronic lymphocytic leukemia (CLL). Among these, ibrutinib is the only one approved in the front-line (1L) setting for patients with or without del(17p) or TP53 mutations. This study aims to compare healthcare resource utilization (HRU), costs, and time to next treatment (TTNT), following initiation of 1L ibrutinib single agent versus CIT and in particular bendamustine/rituximab (BR), in real-world.Methods: The Optum Clinformatics® Extended DataMart De-Identified Databases (01/2004-06/2017) was used to identify adults with CLL diagnosis initiating 1L ibrutinib single agent or CIT (index date) on 02/12/2014 or after. For CIT, only combinations of chemotherapy and CD20 antibody agents recommended by the National Comprehensive Cancer Network guidelines were considered. Patients were also required to have ≥12 months and ≥30 days of continuous eligibility pre- and post-index date, respectively. For each comparison, patients' baseline characteristics were balanced using inverse probability of treatment weighting (IPTW). HRU, costs, and TTNT, were evaluated over 1L therapy. Mean monthly cost differences (MMCD) and rate ratios (RR) obtained from generalized linear models were used to compare costs and HRU, respectively, along with 500-sample bootstrap confidence intervals and P-values. TTNT was defined as the time from initiation of 1L treatment to the initiation of a new antineoplastic agent that was not part of the 1L regimen. TTNT comparisons were performed using Kaplan-Meier (KM) curves with log-rank tests. The hazards of initiating a new treatment were compared between the cohorts using hazard ratios (HRs) obtained from Cox models.Results: Of 1,161 1L patients, 322 initiated ibrutinib and 839 initiated CIT, including 455 on BR. After IPTW, cohorts had comparable baseline characteristics. CIT patients had significantly more days with outpatient (OP) services (RR=0.75; P<0.05), mainly driven by antineoplastic drug administration-related OP visits (Fig.1; P<0.0001). Ibrutinib patients incurred significantly higher pharmacy costs (MMCD=$6,849; P<0.0001) that were fully offset by lower medical costs (MMCD=-$10,615; P<0.0001), resulting in net monthly total cost reduction of $3,766 (P<0.0001; Fig. 2) vs. CIT patients. While no significant difference was observed in the number of days with other OP visits (i.e., not related to antineoplastic treatment), the corresponding cost was significantly lower in ibrutinib patients (MMCD=-$1,002; P=0.0120).Ibrutinib patients also had fewer OP visits compared to BR patients, mainly due to drug administration-related OP visits (Fig. 1). Relative to BR, ibrutinib patients' higher pharmacy costs (MMCD=$7,002; P<0.0001) were fully offset by lower medical costs (MMCD=-$12,571; P<0.0001), yielding monthly reduction in the total cost of care of $5,569 (P<0.0001; Fig. 2).KM analysis of TTNT revealed that, at 24 months post-index, 88.6% of ibrutinib patients did not initiate a new treatment compared to 75.9% among CIT patients (log-rank P=0.0347; Fig. 3A). The hazard of initiating a new treatment was also lower for ibrutinib when compared to CIT, with significant HRs of 0.30 (P=0.0045), 0.59 (P=0.0415), and 0.54 (P=0.0171) at 3, 18, and 24 months post-index, respectively (Fig. 3A). The proportion of patients who did not initiate a new treatment 24 months post-index was significantly higher in ibrutinib cohort than in BR cohort (89.0% versus 79.0%; log-rank P=0.0421). The hazard of initiating a new treatment was also lower for ibrutinib compared to BR, with significant HRs of 0.40 (P=0.0449), 0.54 (P=0.0410), 0.55 (P=0.0360), 0.57 (P=0.0346), and 0.54 (P=0.0219) at 3, 9, 12, 18, and 24 months post-index, respectively (Fig. 3B).Conclusion: During 1L CLL treatment, ibrutinib patients had higher pharmacy costs that were fully offset by lower medical costs, resulting in net total cost reduction compared to CIT or BR patients. In addition to fewer OP visits and lower OP costs related to the antineoplastic treatment, ibrutinib was also associated with lower cost in other OP services. TTNT was significantly longer among ibrutinib patients vs. CIT or BR patients. Furthermore, consistent with the high rates of progression-free survival observed among ibrutinib patients in clinical trials, nearly 90% of patients did not initiate a new treatment after 24 months of follow-up. [Display omitted] DisclosuresWang:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. Emond:Janssen Scientific Affairs, LLC: Research Funding. Romdhani:Janssen Scientific Affairs, LLC: Research Funding. Lefebvre:Janssen Scientific Affairs, LLC: Research Funding. Sundaram:Johnson & Johnson: Employment, Equity Ownership, Other: Travel; AbbVie: Employment, Equity Ownership, Other: Travel. Mato:TG Therapeutics: Research Funding; Regeneron: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Sunesis: Honoraria, Research Funding; Prime Oncology: Speakers Bureau; Abbvie: Consultancy; Acerta: Research Funding; AstraZeneca: Consultancy; Celgene: Consultancy.

Combination of paclitaxel and a LAG-3 fusion protein (eftilagimod alpha), as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Final results from the run-in phase of a placebo-controlled randomized phase II.

1050Background: Eftilagimod alpha (efti, previously IMP321) is a recombinant LAG-3Ig fusion protein that binds to MHC class II and mediates antigen-presenting cell (APC) activation followed by CD8 ...

Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial

The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0-3 were randomly assigned to receive four courses of methotrexate 3·5 g/m2 on day 1 plus cytarabine 2 g/m2 twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m2 on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m2 on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after induction treatment, with adequate autologous peripheral blood stem-cell collection, and without persistent iatrogenic side-effects, were eligible for the second randomisation between WBRT (photons of 4-10 MeV; five fractions per week; fraction size 180 cGy; started within 4 weeks from the last induction course; group D) and carmustine-thiotepa conditioned ASCT (carmustine 400 mg/m2 on day -6, and thiotepa 5 mg/kg every 12 h on days -5 and -4, followed by reinfusion of autologous peripheral blood stem cells; group E). A permuted block randomised design was adopted for both randomisations, and a computer-generated randomisation list was used within each stratum. No masking after assignment to intervention was adopted. The primary endpoint was 2-year progression-free survival, with induction group and response to induction chemotherapy as stratification parameters. Analyses were done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01011920. Between Feb 19, 2010, and Aug 27, 2014, 227 patients were recruited from 53 centres in five countries. 219 of 227 enrolled patients were assessable. Of the 122 patients eligible for the second randomisation, 118 patients were randomly assigned to WBRT or ASCT (59 patients per group) and constitute the study population. WBRT and ASCT were both effective, and achieved the predetermined efficacy threshold of at least 40 progression-free survivors at 2 years among the first 52 patients in both groups D and E. There were no significant differences in 2-year progression-free survival between WBRT and ASCT: 80% (95% CI 70-90) in group D and 69% (59-79) in group E (hazard ratio 1·50, 95% CI 0·83-2·71; p=0·17). Both consolidation therapies were well tolerated. Grade 4 non-haematological toxicity was uncommon; as expected, haematological toxicity was more common in patients treated with ASCT than in those who received WBRT. Two toxic deaths (infections) were recorded, both in patients who received ASCT. WBRT and ASCT are both feasible and effective as consolidation therapies after high-dose methotrexate-based chemoimmunotherapy in patients aged 70 years or younger with primary CNS lymphoma. The risks and implications of cognitive impairment after WBRT should be considered at the time of therapeutic decision. Agenzia Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Science Foundation.

1144O - Phase III randomized controlled trial of adjuvant chemoimmunotherapy in patients with resected primary lung cancer

1144O - Phase III randomized controlled trial of adjuvant chemoimmunotherapy in patients with resected primary lung cancer

Impact of gender on outcome after chemoimmunotherapy in patients with chronic lymphocytic leukemia: a meta-analysis by the German CLL study group.

Impact of gender on outcome after chemoimmunotherapy in patients with chronic lymphocytic leukemia: a meta-analysis by the German CLL study group

Combination of paclitaxel and LAG3-Ig (IMP321), a novel MHC class II agonist, as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Interim results from the run-in phase of a placebo controlled randomized phase II.

1062 Background: IMP321 is a recombinant soluble LAG3-Ig fusion protein that binds to MHC class II molecules and mediates antigen-presenting cell (APC) activation followed by CD8 T-cell activation. The activation of the dendritic cell network with IMP321 the day after a low dose injection of a single agent chemotherapy may lead to stronger anti-tumor CD8 T-cell responses. We report initial results of the safety run-in of a randomized, placebo-controlled phase IIb trial in patients (pts) with hormone receptor positive (HR+) MBC receiving first-line weekly paclitaxel. Methods: In the safety run-in phase 15 pts with MBC received weekly paclitaxel (80 mg/m2; D1, D8, D15) in a four week cycle in conjunction with either 6 mg (n = 6; cohort 1) or 30 mg (n = 9, cohort 2) IMP321 injections s.c. (D2 and D16) for 6 cycles. Patients without progressive disease could continue with a maintenance phase of 12 additional injections of IMP321 every 4 weeks. Blood samples for pharmacokinetics and immuno-monitoring were taken in cycle 1 and 4 just before and after IMP321 injection. Results: In total 15 pts (median age 53 years) were enrolled between Jan 2016 and Oct 2016. No dose limiting toxicities have been reported. Cytokine release syndrome grade 1 was the only serious adverse event (SAE) related to IMP321 and occurred twice in the same patient. Grade 1 and 2 injection site reactions were the most common related AEs and occurred in 14 pts (93 %). A dose-dependent increase in serum IMP321 concentration was observed among the two dose levels with a Cmaxbetween 4 and 24 hours. Increased number of circulating monocytes, dendritic cells and increased activation were observed at both dose levels of IMP321, supporting the working hypothesis. Conclusions: The 30 mg s.c. IMP321 given every two weeks in combination with weekly paclitaxel is the recommended phase 2 dose which is used in the ongoing randomized placebo controlled phase II part of the study. Clinical trial information: NCT02614833.

Three-year survival after combined treatment with induction chemoimmunotherapy in patients (pts) with non-small cell lung cancer (NSCLC).

e20064 Background: Induction chemotherapy (iCT) for NSCLC has potential advantages over adjuvant CT, high therapeutic compliance, the ability to influence the primary tumor and metastatic disease. Standard approaches to iCT improving are largely exhausted. However, the development of iCIT techniques using recombinant cytokines and assessment of the effectiveness of its clinical application remains poorly understood. Methods: Clinical trial included 65 pts. with stage IIB, IIIA (N2), IIIB (T4 ipsi. nod.) NSCLC, randomized in main (n = 33) and control (n = 32) groups with comparable clinical and pathological characteristics: m 23 (69.7) vs. 23 (71.8%), W 10 (30,3%) vs. 9 (28.2%); stage IIB - 8 (24.4%) vs. 9 (28.6%), IIIA - 22 (66.6%) vs. 19 (59.4%), IIIB - 3 (9%) vs. 4 (12.5%); 40-49 years 5 (15,5%) vs. 5 (15,6%), 50-59 14 (42,4%) vs.15 (46,8%), 60 years and older 14 (42,4%) vs. 12 (37,8%). Pts. of the control group received 2 iCT cycles: cisplatin 75 mg / m2 i.v. 1 day and gemcitabine 1000 mg / m2 i. v. 1 and 8 days; pts. of the main group additionally received recombinant tumor necrosis factor coupled with thymosin (TNF-T Farmaclon Russia) 50. 000 ED / m2i.v. 3, 5 and 7 days of the cycle. The direct results were evaluated 3 weeks after completion of induction. Pts. who underwent radical surgery received 2 cycles of platinum-based adjuvant CT. DFS was studied by the method of Kaplan-Meier. Results: 3-year DFS in the main group was 72% vs. 48% in the control group (p = 0.10603). Conclusions: Clinical trial of the effectiveness of iCIT with using immune drug TNF-T demonstrated a tendency to improve 3-year DFS by 24%, which favors further studies on a larger number of pts.

Consolidation anti-CD22 fractionated radioimmunotherapy with 90Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial

Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD22 90Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma. We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/m2], cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], and vincristine [1·4 mg/m2, up to 2 mg] all on day 1, and prednisone [40 mg/m2] daily for 5 days), administered every 14 days. 6-8 weeks after R-CHOP, responders received two doses of 15 mCi/m2 (555 MBq/m2) 90Y-epratuzumab tetraxetan administered 1 week apart. The primary endpoint was 2 year event-free survival in all registered eligible patients who received at least 1 day of study treatment; the safety analysis was done in the same population. This trial is registered with ClinicalTrials.gov, number NCT00906841. Between Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving radioimmunotherapy. Fractionated radioimmunotherapy with 90Y-epratuzumab tetraxetan might be appropriate for response consolidation after induction chemotherapy in older patients with advanced diffuse large B-cell lymphoma, but further comparative studies are needed. Immunomedics, Amgen, Canceropôle Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d'Avenir).

Effects on Survival and Neurocognitive Functions of Whole-Brain Radiotherapy (WBRT) and Autologous Stem Cell Transplantation (ASCT) as Consolidation Options after High-Dose Methotrexate-Based Chemoimmunotherapy in Patients with Newly Diagnosed Primary CNS Lymphoma (PCNSL): Results of the Second Randomization of the IELSG32 Trial

Effects on Survival and Neurocognitive Functions of Whole-Brain Radiotherapy (WBRT) and Autologous Stem Cell Transplantation (ASCT) as Consolidation Options after High-Dose Methotrexate-Based Chemoimmunotherapy in Patients with Newly Diagnosed Primary CNS Lymphoma (PCNSL): Results of the Second Randomization of the IELSG32 Trial

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

AbstractThe safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135.

In Vivo Purging May Not be Required in the Era of Universal Use of Rituximab Containing Chemo-Immunotherapy in Patients with Follicular and Mantle Cell Lymphoma: A Single Center Experience

In Vivo Purging May Not be Required in the Era of Universal Use of Rituximab Containing Chemo-Immunotherapy in Patients with Follicular and Mantle Cell Lymphoma: A Single Center Experience

Consolidative Radioimmunotherapy after Chemoimmunotherapy in Patients with Histologic Transformation of Indolent Lymphoma

Abstract Introduction:Histologic transformation (HT) has been well characterized in follicular lymphoma (FL), and has historically carried a poor prognosis with median overall survival (OS) of 1.2-1.8 years (yrs) in the pre-rituximab era (Montoto et al, 2007; Al-Tourah et al 2008). Despite improved outcomes in the rituximab era (Link et al, 2013), HT still represents a major source of mortality and morbidity in these patients (pts). While there is emerging evidence that autologous stem cell transplant (ASCT) confers a survival advantage compared to chemotherapy with rituximab alone (Ban-Hoefen et al, 2013; Villa et al, 2013), many of these patients have contraindications such as advanced age and frailty precluding ASCT as an option. We report a strategy of radioimmunotherapy (RIT) consolidation after chemoimmunotherapy to address this unmet need. Methods: Consecutive pts ≥ 18 yrs old, who received RIT as consolidation after chemoimmunotherapy for HT at the Wilmot Cancer Institute were identified who had been deemed ineligible for ASCT. Inclusion criteria were as follows: 1) clinical, composite or pathologic diagnosis of HT, and 2) receipt of RIT after response to rituximab and chemotherapy. HT was defined as biopsy confirmed diffuse large B cell or Burkitt-like lymphoma by the WHO classification ≥6 months following a biopsy establishing indolent lymphoma diagnosis (pathologic HT), or clinical evidence of transformation as defined in previous cohorts (Al-Tourah et al, 2008; Link et al, 2013) in the absence of biopsy confirmation (clinical HT). Composite diagnosis of HT was defined as concurrent indolent and large cell lymphoma. The primary endpoint was overall survival (OS). Progression free survival (PFS) was a secondary outcome. Kaplan-Meier survival estimation curves were generated using SAS (SAS Institute Inc., Cary, NC, USA), and p values were generated using the log rank test. Results: 21 consecutive pts who had a clinical, composite, or pathologic HT diagnosis were included in this analysis. All of these pts responded to rituximab and chemotherapy (CHOP like n=18, other n=3), and were treated with RIT for consolidation. The median age at the time of HT was 66 yrs (44-90). Nine pts received I-131 tositumomab and 12 received Y-90 ibritumomab tiuxetan. The median OS from HT was 6.9 yrs in the entire cohort with a median follow up of 3.5 yrs (Figure). There were no statistical differences in outcomes between the pathologic (n=11) and clinical/composite (n=10) HT pts (p=0.33). There was also no difference between those who received rituximab prior to HT (n=13), and those who did not (n=8; p=0.88). Twelve pts experienced grade 3-4 thrombocytopenia, which was the most common adverse event (AE). Nine deaths occurred. Disease-related death was the most common cause (n=4), followed by death unrelated to disease or treatment (n=3) and treatment-related death (n=2). Figure: Kaplan-Meier estimate of OS after HT in pts receiving RIT after chemoimmunotherapy (n=21) Figure:. Kaplan-Meier estimate of OS after HT in pts receiving RIT after chemoimmunotherapy (n=21) Conclusions: We report the use of RIT as consolidation of response to chemoimmunotherapy in pts with HT. This represents one of the largest series focused on pts with HT who were deemed unfit for ASCT. The RIT was well tolerated in this analysis with only 2 treatment related deaths, one of which was secondary to therapy related acute myeloid leukemia. Our observed median OS compares favorably to published reports of pts with HT who are younger and able to tolerate more aggressive therapeutic options. Consolidative RIT should be considered as a treatment approach in this vulnerable population of pts, and can serve as a platform for the incorporation of novel agents into prospective clinical trials. Disclosures Barr: Pharmacyclics: Research Funding.

18F-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma: results of a Nordic/US intergroup study

We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1–3 considered negative (D 5PS > 3) and D 5PS with scores 1–4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.

SIE, SIES, GITMO revised guidelines for the management of follicular lymphoma

By using the GRADE system, we updated the guidelines for management of follicular cell lymphoma issued in 2006 from SIE, SIES, and GITMO group. We confirmed our recommendation to frontline chemoimmunotherapy in patients with Stage III-IV disease and/or high tumor burden. Maintenance rituximab was also recommended in responding patients. In patients relapsing after an interval longer than 12 months from frontline therapy, we recommended chemoimmunotherapy with non cross-resistant regimens followed by rituximab maintenance. High dose chemotherapy followed by hematopoietic stem cell transplant was recommended for young fit patients who achieve a response after salvage chemoimmunotherapy.

Improving treatment for patients with chronic lymphocytic leukemia

The last two decades have been time of tremendous progress in treatment for patients with chronic lymphocytic lymphoma (CLL). Chemoimmunotherapy (CIT) combining anti-CD20 monoclonal antibodies with purine nucleoside analogs has been a substantial advance for patients with CLL and results in increased response rates, progression-free survival, and overall survival. Despite these improved outcomes, only ∼45% of patients achieve a complete remission with CIT and nearly all patients eventually relapse and their remains a need to improve efficacy. Although new combinations of traditional agents may lead to incremental progress, more substantive improvements are likely to result through therapeutic targeting of novel pathways critical to CLL B-cell survival including targeting: (1) leukemia cell apoptotic resistance; (2) survival signals mediated through the B-cell receptor; and (3) nurturing interactions with the microenvironment. In this mini-review, we summarize Mayo Clinic’s recent efforts to improve CIT for patients with CLL.