Last Cycle Of Treatment Research Articles

Neoadjuvant Immunotherapy in Oncogene-Positive Non-Small Cell Lung Cancer: A Multicenter Study

BackgroundPreoperative immunotherapy has shed light on the management of resectable non-small cell lung cancer (NSCLC). However, whether neoadjuvant immunotherapy benefits patients with oncogene-positive NSCLC remains unknown. MethodsData were retrieved from 4 institutions in the period from August 2018 to May 2021. Eligible patients were aged ≥18 years with histologically confirmed stage IIA to stage IIIB (T1-2 N1-2 or T3-4 N0-2) NSCLC that was deemed to be surgically resectable. The neoadjuvant regimen included immune checkpoint inhibitors alone or in combination with platinum-based doublets. Surgical resection was performed 4 to 6 weeks after the first day of the last cycle of treatment. The primary end point was major pathologic response (MPR; ≤10% viable tumor cells). Analyses were categorized according to the patients’ oncogene (EGFR, ALK, KRAS, MET, BRAF, ROS1, RET) status. ResultsOverall, 137 patients were identified; 46 (33%) patients had nonsquamous cell cancer, and 114 (83%) had stage IIIA/B disease. Oncogene alterations were identified in 22 (16%) patients, of whom only 2 patients (2/22 [9%]) had an MPR compared with 65 (65/115 [56.5%]) in the oncogene-negative population (P < .001). Similar results were retained after propensity score matching for age, sex, smoking status, histologic type, stage, and cycles of neoadjuvant treatment. Squamous cell carcinoma (odds ratio, 2.54; 95% CI, 1.08-5.99) and positive oncogene status (odds ratio, 0.13; 95% CI, 0.03-0.64) were found to be indicators for MPR by logistic regression. The 1-year event-free survival rate was 75.4% in the oncogene-positive group, which was not significantly different from 85.5% in the oncogene-negative population (P = .23). ConclusionsPatients with stage II-III oncogene-positive NSCLCs respond less than patients with oncogene-negative NSCLCs after neoadjuvant immunotherapy.

Isolated CNS relapse of medullary aggressive high-grade B-cell lymphoma on 18F-FDG-PET/CT

This is a case of high-risk, aggressive, high-grade medullary B-cell lymphoma presenting with new onset of neurological dysfunction following initial complete response to the standard chemoimmunotherapy. A whole-body re-staging PET using fluorodeoxyglucose (18F-FDG) integrated with computed tomography (18FDG-PET/CT) performed with clinical suspicion of arachnoiditis, eloquently demonstrated unequivocal multifocal FDG uptake by the spinal cord without evidence of systemic recurrence, leading to a clinical diagnosis of secondary CNS lymphoma, which is a rare complication of DLBCL with ominous prognosis. Four cycles of Modified-MATRIX protocol resulted in a halt in fulminant course of the disease and the patient experienced slight reversal of the neurological deficits, although not deemed clinically fit for a repeat 18FDG-PET/CT due to his poor general well-being. Repeat MRI was suggestive of partial recovery, however. The clinical stability was proven short-lived, and the patient experienced progressive lower limb weakness only 3 weeks after discharge following his last cycle of treatment. Isolated CNS relapse of lymphoma is a rare occurrence in the literature. The CNS recurrence is more often leptomeningeal or confined to the brain parenchyma rather than the spinal cord. The role of 18FDG-PET/CT in the diagnostic algorithm of secondary CNS lymphoma is unclear and its significance in risk stratification and assessing the response to treatment has not been evaluated. This case report illustrates the imaging findings of a more unusual form of the disease with multifocal intramedullary involvement of the spinal cord, and highlights imaging features of this rare condition with 18FDG-PET/CT and MRI to support decision making in good clinical practice.

Low Incidence of COVID-19 Infection in Patients with Acute Myeloid Leukemia Undergoing Reduced Intensity/Venetoclax Based Treatment: Initial Results of the PACE Prospective Clinical Study from the UK Trials Acceleration Program

Low Incidence of COVID-19 Infection in Patients with Acute Myeloid Leukemia Undergoing Reduced Intensity/Venetoclax Based Treatment: Initial Results of the PACE Prospective Clinical Study from the UK Trials Acceleration Program

Phase II trial of toripalimab plus chemotherapy as neoadjuvant treatment in resectable stage III non-small cell lung cancer (NeoTPD01 Study).

8541 Background: Multi-modality treatment provides modest survival benefits for locally advanced non-small-cell lung cancer (NSCLC) patients. Preoperative immunotherapy has continuously been shown to be promising in treating resectable NSCLC. The current study aimed to investigate the activity and safety of the PD-1 inhibitor, toripalimab, with chemotherapy given as neoadjuvant treatment for resectable stage III NSCLC in Asian population. Methods: Eligible patients recruited were aged 18 years or older with histologically confirmed AJCC-defined stage IIIA or T3-4N2 IIIB NSCLC who deemed surgically resectable. Patients received 3 cycles of neoadjuvant treatment with intravenous toripalimab (240 mg), carboplatin (area under curve 5), and pemetrexed (500 mg/m2 for adenocarcinoma) or nab-paclitaxel (260 mg/m2 for others) on day 1 of each 21-day cycle. Surgical resection was performed 4-5 weeks following the first day of the last cycle of treatment. The primary endpoint was major pathological response (MPR; ≤10% viable tumor cells). Secondary endpoints included pathological complete response (pCR), R0 resection rate, disease-free survival and safety. Paired primary tumor +/- lymph node and blood samples at baseline and surgery were obtained for exploratory study. This study is registered with ClinicalTrials.gov, NCT04304248. Results: Between August 2019 and July 2020, 33 patients (median age: 61, IQR: 56-66; female: 6, 18.2%) were enrolled and received neoadjuvant treatment. 18 (54.5%) patients had squamous cell lung cancer, and 13 (39.4%) had T3-4N2 stage IIIB disease. Two patients refused surgery and one had progressive disease after treatment. 30 (91.9%) patients underwent resection (median interval between neoadjuvant treatment and surgery: 36.5 days, IQR 30-42.5) and all except one achieved R0 resection (29/30, 96.7%). 20 patients (20/30, 66.7%) had an MPR, including 15 patients (15/30, 50.0%) had a pCR in the per-protocol population. Surgical complications included three arrhythmias, one prolonged air leak, and one chylothorax. 24 patients (80.0%) had pathological downstaging following treatment, and complete lymph node clearances (ypN0) were seen in 70.0% (21/30) of patients. The most common grade 3-4 treatment-related adverse events in the intention-to-treat population were anemia (2, [6.0%]). Severe treatment-related adverse event included one (3.0%) patient with grade 3 peripheral neuropathy (Guillain-Barré syndrome) and resulted in surgery cancellation. At the time of data cutoff (Feb 7, 2021), the median duration of follow-up was 4.13 months, and there were no treatment-related deaths. Conclusions: Toripalimab plus platinum-based doublet yields a high MPR rate, manageable treatment-related toxicity, and feasible surgical resection in resectable stage III NSCLC. Ongoing analysis of biomarker will be available at the meeting. Clinical trial information: NCT04304248.

Interaction of Remission Status and Cause of Death in Acute Myeloid Leukemia

BACKGROUND: Historically, causes of death for patients dying with active acute myeloid leukemia (AML) and those in remission have differed. However, it is unknown how changes in therapies and advances in supportive care have impacted death patterns and whether these differ for patients with active disease or those in morphologic remission (with or without measurable residual disease [MRD]) at the time of death. Here, we investigated the cause of death (COD) in AML patients and studied whether these differed for patients in morphologic remission with or without evidence of MRD. PATIENTS AND METHODS:We used an institutional database of adults with newly-diagnosed AML treated with intensive induction chemotherapy from 2006-2017 with either "7+3" (N=140) or cladribine, cytarabine, mitoxantrone and G-CSF ("CLAG-M", N=198). Primary COD, time of death (TOD) and clinical variables were abstracted from chart review. Disease status at TOD was determined by the patient's last bone marrow aspirate/biopsy (BMA) prior to death, unless complete blood count or autopsy clearly showed AML. Complete remission (CR), CR with incomplete hematologic recovery (CRi), and relapse were defined per 2017 ELN criteria. MRD was determined by multiparameter flow cytometry (MFC) and cytogenetics on all BMA. All patients treated on clinical studies gave informed consent in accordance with the Declaration of Helsinki and were treated on Institutional Review Board-approved protocols. RESULTS: Characteristics of the 338 patients are shown in Table 1. With a median follow-up of 928 days, 187/338 (55%) patients died, 2 of which were excluded from subsequent analysis due to incomplete data. The remaining 185 patients were categorized into 3 groups based on disease status at TOD: remission (CR/CRi and MRD negative), MRD (CR/CRi and MRD positive), and relapse. There were 59 (32%) patients in remission, 13 of which had treatment following their last BMA; this treatment consisted of consolidation chemotherapy or transplant in 11/13 patients. There were 17 (9%) MRD patients and in 6/17 the response to last cycle of treatment was unknown. 109 (59%) of patients were in relapse at TOD, and 24/109 were without BMA assessment following last treatment. 36/59 (61%) remission patients underwent hematopoietic cell transplantation, compared to 5/17 (29%) and 42/109 (39%) in the MRD and relapse groups, respectively. Overall, the median survival from the start of initial induction treatment to death was 327 days, with 85/185 (45%) of patients dying within 60 days of their last treatment. Median time between last cycle of treatment and death was 136 days for the remission group, compared to 53 days in MRD and 50 days in relapse groups. Finally, we examined how COD varied by disease status at time of death (Table 2). Of patients dying with morphologic AML (N=109), AML was the most common COD (45%) followed by infection (33%), other (9%), and unknown (7%). For remission patients (N=59), infection was the predominant COD (56%) followed by unknown (17%) and transplant-related complications (12%). In MRD positive patients (N=17), AML was the COD in 1 patient (6%), infection occurred in 6 (35%), with unknown (29%) or other causes (18%) accounting for the remaining deaths. Notably, only 9 (5%) of patients underwent autopsy and of the 50 patients dying with AML as primary cause, the majority (32/50, 64%) died while on hospice and thus AML as primary cause was presumptive. CONCLUSIONS: In our cohort, the majority of deaths occurred within one year of starting induction chemotherapy, and most occurred in patients in active relapse. Only a minor subset of patients dying in morphologic remission had MRD, and COD of patients in the MRD group more closely reflected that of patients in remission. A substantial proportion of deaths occurred within 60 days of treatment, demonstrating that active treatment represents a particularly vulnerable period for patients regardless of disease status. Infection accounted for a substantial proportion of deaths for patients in all disease categories, and is likely undercounted in our study given the high proportion of relapse patients dying on hospice. Thus, despite advances in treatment, infection represents the most common cause of death in AML, highlighting the need for advances in diagnosis and treatment of infections to improve overall outcomes. Disclosures Halpern: Novartis: Other; Bayer: Other; Jazz Pharmaceuticals: Other; Imago BioSciences: Other; Tolero Pharmaceuticals: Research Funding. Walter:Aptevo Therapeutics: Research Funding. Godwin:Pfizer Inc.: Research Funding; Immunogen Inc.: Research Funding.

Scalp cooling to prevent chemotherapy induced alopecia (CIA) in black patients: Differences in efficacy?

12101 Background: The Paxman scalp cooling device has been used for over 20 years to prevent CIA, obtaining FDA clearance in the U.S. in 2017. Prior studies reported 50-80% success and high patient satisfaction yet included few or no black patients. In the U.S. this may reflect disparities in access due to cost, awareness, or availability. We opened a prospective observational study combining patient-reported outcomes with clinical assessments of alopecia and planned to deliver scalp cooling to 30 black patients receiving chemotherapy for breast cancer. Methods: Patients who self-identified racially as black, had a new diagnosis of stage I-III breast cancer, and planned to receive chemotherapy with taxane-containing regimens were eligible. Anthracycline (AC) and non-anthracycline (NAC) chemotherapy agents were included; costs for the intervention were covered by Paxman and internal philanthropic funding. Patients who declined scalp cooling were approached for enrollment as controls. Primary endpoints were grade of alopecia as measured by providers and patient self-report using Modified Dean Scale and Visual Analog Scale (VAS) respectively. Hair preservation was defined as &lt;50% hair loss (&lt;grade 2) by Dean and score &lt; 50 on VAS. Secondary endpoints were alopecia by NCI grading scale and psychosocial from CADS and EORTC QLQ BR45 questionnaires. Results: 15 out of 30 planned participants enrolled by February 2020 with interim analysis and hold in accrual due to lack of efficacy. Four patients remain on treatment. Of 11 scalp cooling patients who completed chemotherapy, 0 prevented significant alopecia. Nine discontinued use of scalp cooling before completion (1 due to scheduling, 8 due to &gt;grade 3 alopecia). The 2 patients who used scalp cooling for the duration had &gt;grade 3 alopecia before the last cycle of treatment. Conclusions: Scalp cooling is an important supportive therapy that can reduce chance of alopecia, a bothersome side effect for patients. Our experience indicates decreased efficacy in black patients with both AC and NAC regimens. This is an important negative result to explore. Discussions with the Paxman team and providers with expertise in alopecia are underway to explore contributing factors such as hair thickness, prior hair treatments, and cap design. [Table: see text]

Prognostic importance of prostatic specific antigen response in patients who received Lutetium-177 prostate-specific membrane antigen treatment for castration resistant prostate cancer.

This study aims to analyze the prognostic importance of serum prostate specific antigen (PSA) response in patients who received radioligand therapy (RLT) with Lu-177 Prostate-specific membrane antigen (PSMA) for their castration-resistant prostate cancer. Thirty consecutive patients who received Lu-177 PSMA treatment for their castration-resistant prostate carcinoma were included. All the patients had undergone Ga-68 PSMA PET/CT scanning before Lu-177 PSMA therapy, which revealed multiple metastases. Patients were treated with a fixed dose (180 mCi) of Lu-177 PSMA at six to eight weeks intervals. PSA response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Serum PSA response was classified as PSA progression (25% increase over the baseline and an increase in the absolute-value PSA level by at least 5 ng per millilitre), any <50% decline or ≥50% decline. PSA response was evaluated six weeks after every cycle. Response evaluation with radiological imaging and Ga-68 PSMA PET/CT were performed before the first cycle and eight weeks after the last cycle. Thirty patients were treated with a total of 171 cycles (median 4, range 3-7) of Lu-177 PSMA. A decline in serum PSA of ≥50% was detected in ten patients (33%) while a decline in PSA of any amount was observed in fifteen (50%) patients after the first cycle. After the last cycle, a decline in PSA ≥50% and of any amount was seen in thirteen (43%) and fourteen (46%) patients, respectively. Of the fifteen patients who were not responder after the first cycle, three (20%) had a decline in PSA of any amount after the completion of the RLT. Moreover, of the 20 patients who did not have a ≥50% decline in PSA level after the first cycle, four (20%) became responder after the last cycle. Regarding serum PSA response after the first cycle, median OS was significantly higher for patients who had ≥50% decline in PSA level with 21.0±10.0 (95% CI: 1.2-40.7) months compared to patients who had not with 8.0±2.6 (95% CI: 2.7-13.2) months (P=0.012). A decline in PSA of any amount after the first cycle did not have a significant impact on median OS (12.0±1.1 vs. 6.0±2.5 months, P=0.08). The decline in serum PSA level after the last cycle of treatment had a significant impact on OS. Median OS for the decline in PSA of any amount was calculated as 13.0±1.0 (95% CI: 10.9-15.0) months for responders and 6.0±1.9 (95% CI: 2.2-9.7) months for non-responders (P=0.016). Considering ≥50% of decline as a response, median OS was 21.0±5.8 (95% CI: 9.5-32.4) months for responders and 6.0±3.0 (95% CI: 0.1-11.8) months for non-responders (P=0.026). Serum PSA level during RLT with Lu-177 PSMA remains a clinically significant factor to predict OS times. About twenty percent of patients who were not responder after the first cycle could become responder after the last cycle. However, patients without PSA response after completion of all cycles should be closely followed-up. Non-responder patients can achieve a response with further treatments.

PS1371 ELOTUZUMAB IN COMBINATION WITH CARFILZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (KRD) IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): A PHASE 2 MMRC TRIAL

Background:Several recent studies have showed improved results with addition of antibodies to anti‐myeloma regimens. The KRd combination is highly active in NDMM. We hypothesized that addition of elotuzumab (ELO) to KRd (E‐KRd combination) would improve efficacy as compared to KRd.Aims:We report interim response data at key landmark timepoints of the studyMethods:The study has enrolled newly diagnosed patients (pts) requiring treatment as per IMWG criteria, regardless of transplantation eligibility. Per protocol, pts receive 12–24 cycles of E‐KRd, with adaptive design of the duration of E‐KRd treatment based on sustained MRD‐negativity by next gene sequencing (NGS) clonoSEQ (Adaptive Biotechnologies), followed by E‐Rd maintenance. ELO is given at 10 mg/kg QW for Cycles 1–2, Q2W for Cycles 3+, and Q4W during E‐Rd maintenance. Carfilzomib (K) is administered on Days 1, 8 and 15 of each 28‐day cycle, 20 mg/m2 on C1D1, then escalated up to 56 mg/m2 or 70 mg/m2 based on tolerability. Lenalidomide 25 mg is given on Days 1–21 and dexamethasone 20–40 mg per week. Per protocol, transplant candidates undergo stem cell collection after C4 using G‐CSF plus plerixafor, and then resume E‐KRd treatment. Pts who choose to discontinue treatment to receive autologous stem cell transplant (ASCT) are censored from the analysis at the time of their last cycle of treatment. Landmark evaluations are performed after 4, 8, 12, 18, and 24 cycles and include MRD evaluation using multi‐color flow cytometry (MCF) with 10–5 sensitivity and by NGS with 10–5–10–6 sensitivity, and by Mass Spectrometry (MassSpec) for sCR confirmation. A total of 40, transplant ineligible and/or transplant eligible pts who agree to defer ASCT will be enrolled as well as an additional 15 pts who plan to proceed to ASCT. The primary end‐point of the study is sCR/MRD(‐) rate after 8 cycles of E‐KRd therapy for the transplant ineligible/deferred pts and sCR/MRD(‐) rate at the end of 4 cycles for all enrolled pts.Results:Twenty‐four pts (median [range] age 61, [46–81]) were enrolled, of which 11 pts (46%) had IMWG high‐risk cytogenetics, including 5 pts (21%) with del p53. At the cut‐off date Feb 21, 2019, pts received a median of 4 (1–20) treatment cycles. Per protocol criteria, 10 pts escalated carfilzomib dose to 70 mg/m2. Median (range) duration of follow‐up was 9.7 (1–19) months. Four (17%) pts discontinued treatment (1 adverse event [cardio‐pulmonary toxicity]; 1 elective ASCT and 2 progressive disease). In intent‐to‐treat (ITT), ORR was 100% (50% CR/sCR, 95% at ≥VGPR (N = 22, 2 of 24 pts are too early to assess, &lt;1 cycle); all pts achieved at least PR after C1 with CR/sCR rates 36% and 60% at the end of 4 and 8 cycles, respectively. For the ITT population, MRD(‐) rates were 70% by MFC at the end of 4 cycles (N = 20) and 70% by MFC (N = 10) and 56% by NGS (N = 9) at the end of 8 cycles. The most common non‐hematological AEs (all grades) were fatigue (63%), fever (33%), dyspnea (33%), upper respiratory infection (29%), constipation (25%), diarrhea (25%), and rash (25%). Serious AEs occurred in 9 pts (38%) and 41% pts experiences TEAE. The most common grade 3/4 TEAEs (&gt;10%) were pneumonia (17%) and lymphopenia (13%). No grade 5 TEAE was reported. Updated results, including pending MassSpec analyses and MRD analyses by NGS will be presented at the meeting.Summary/Conclusion:The addition of ELO to KRd demonstrated manageable toxicity profile and promising activity suggestive of possible benefit of adding this agent to KRd, with high rates of deep responses including MRD‐negativity

177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients with a Single Functioning Kidney.

The aim of this study was to assess the safety, tolerability, and effects on renal function as well as therapeutic efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) using 177Lu-labeled PSMA-617 in patients with metastatic castration-resistant prostate cancer and a single functioning kidney before PRLT. Methods: Sixteen patients (aged 53-78 y; mean age, 64.7 ± 6.5 y) with a single functioning kidney received PRLT with 177Lu-PSMA-617 between March 2015 and October 2018. All parameters of renal function (serum creatinine, blood urea nitrogen, and electrolytes) were prospectively documented in a structured database and analyzed before each PRLT cycle and in follow-up. Renal function was further quantified by measuring tubular extraction rate (TER) using 99mTc-mercaptoacetyltriglycine renal scintigraphy. Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Kaplan-Meier analysis was performed to obtain the progression-free survival and overall survival. Results: The median administered activity was 22.1 GBq (range, 15.4-33.8 GBq). The calculated absorbed radiation dose to the kidney per cycle was 5.3 ± 2.1 Gy (0.81 ± 0.32 Gy/GBq). Renal function was already impaired at baseline in 43.7% of patients, including CTCAE grade 1 renal impairment in 25.0% and CTCAE grade 2 in 18.8%. Grade 1 and 2 renal impairment, respectively, were present in 37.5% and 6.3% of the patients after the first PRLT cycle and in 31.3% and 12.5% after the second cycle. No CTCAE grade 3 or 4 nephrotoxicity was observed during or after treatment. There was no significant change in either TER or the ratio of TER to lower-limit TER after the last cycle of treatment (P > 0.05). The median PFS was 8.1 mo based on both the criteria of the European Organization for Research and Treatment of Cancer and RECIST. The median overall survival has yet to be reached with a median follow-up time of 19.3 mo (range, 5.8-45.3 mo). Conclusion: In patients with a single functioning kidney, 177Lu-PSMA-617 PRLT is feasible, seems to be effective, and is well tolerated, without any signs of acute or subacute nephrotoxicity during a mean follow-up of nearly 2 y (and up to 45.3 mo). Further long-term follow-up of this special patient group is warranted.

Chemotherapy-Induced Nausea and Vomiting: An Oncology-Day Unit Experience

Introduction: Chemotherapy-induced nausea and vomiting are the most common side-effects feared by patients. Although significant advances have been made, chemotherapy-induced nausea and vomiting remain an important adverse effect of treatment. Purpose: The purpose of our study was to evaluate the prevalence of chemotherapy-induced nausea and vomiting in an oncology day unit in France. We described then the management of this side-effect. Methods: This retrospective mono-centric observational study assessed 65 patients in our oncology day unit. They all were on chemotherapy for solid tumors and should have had already received one cycle of chemotherapy. Patients were metastatic or treated with a curative intent. During three days, patients were asked if they had experienced nausea and/or vomiting after their last cycle of treatment. Results: 65 patients were enrolled, 45 women (69%) and 20 men (31%). The median age was 63 years. 20 patients were elderly people. 48 patients were metastatic (74%) and 17(26%) were on neo-adjuvant or adjuvant therapy. 24 people (37%) experienced nausea (20 patients) or vomited (4 patients). Nausea was essentially grade I (60%). All patients received anti-emetic therapies. In the 24 patients who suffered from adverse effects, only 6 had corticosteroids, 15 had NK1 receptor inhibitors, 12 received 5-HT3 receptor inhibitors and 12 anti D2 treatments. 9 patients (14%) experienced refractory nausea and vomiting. Conclusion: Even if guidelines exist and despite many therapeutics agents have improved patients’ quality of life in terms of nausea and vomiting, in some cases it seems not to be enough.

Randomized Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab with or without Concurrent Avastin for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL)

BACKGROUND: Although chemoimmunotherapy (CIT) has improved response rates, treatment free survival, and overall survival in patients with chronic lymphocytic leukemia (CLL), only 40-50% of patients achieve a complete remission and the majority have residual disease when evaluated using sensitive assays. Interactions with nurturing environments can enhance CLL B-cell resistance to apoptosis. These interactions include cytokine mediated prosurvival signals by angiogenic molecules, such as VEGF and bFGF that nurture CLL B-cells in an autocrine fashion and promote CLL cell survival partly through up regulation of anti-apoptotic proteins. These findings provide a strong rationale for testing anti-VEGF therapy in combination with a purine nucleoside analogue CIT regimen for upfront treatment. We conducted a randomized phase 2 CIT trial using pentostatin, cyclophosphamide, and rituximab with (PCR-B) or without (PCR) bevacizumab (B), an anti-VEGF monoclonal anti-body.METHODS: Eligible patients were previously untreated and had CLL in need of treatment by NCI-WG criteria (Blood 111:5446). Patients were randomized using a dynamic allocation procedure stratifying for stage (0-II vs. III-IV) and FISH (17p or 11q deletion vs. other) to receive either 6 cycles of rituximab (100 mg on day 1 of cycle 1; 375 mg/m2on day 2 of cycle 1 and day 1 of cycles 2-6) followed by pentostatin (2 mg/m2) and cyclophosphamide (600 mg/m2) (PCR) administered every 21 days. Patients in the PCR-B cohort also received bevacizumab 15mg/kg on day 1 of cycles 1-5 and days 1, 22, & 43 of cycle 6. All patients underwent complete response evaluation 3 months after day 1 of cycle 6 (or last cycle of treatment for those completing < 6 cycles). MRD was assessed using 6-color flow cytometry (Leukemia 21:956) at the completion of treatment.RESULTS: 68 patients were enrolled through the Mayo Clinic Cancer Research Consortium between 1/2009 and 1/2013. Three patients were excluded from analysis: 1 patient canceled prior to treatment, 1 was dosed incorrectly, and 1 was ineligible due to immunophenotyping inconsistent with CLL. Median age of eligible patients was 63 years (range 43-81) and 43 (66%) were men. With respect to disease stage, 3 (5%), 38 (58%), and 24 (37%) had low, intermediate and high Rai stage disease. Eleven (17%) patients had deletion 17p or 11q & 29 (45%) had unmutated IGHV. No statistically significant differences were observed in these variables by treatment arm.All 65 evaluable patients have completed active treatment, with 54 (83.1%) completing the intended 6 cycles (PCR group 27/32 [84.4%] and PCR-B 27/33 [81.8%]). Hematologic grade 3+ adverse events deemed at least possibly related to treatment were observed in 10 (31.3%) patients on PCR and 12 (36.4%) on PCR-B (p=0.79).Non-hematologic grade 3+ adverse events deemed at least possibly related to treatment were observed in 9 (28.1%) patients on PCR and 18 (54.4%) on PCR-B (p=0.04). The most common such events were hypertension (PCR: 3.1% vs. PCR-B: 21.2%), proteinuria (0% vs. 6.1%) and creatinine increase (3.1% vs. 6.1%).Across both arms, 64/65 (98.5%) patients achieved a response including 31/32 (96.9%) treated with PCR and 33/33 (100%) treated with PCR-B (p=0.49). CR/CRi was achieved in 10/32 (31.3%) patients treated with PCR & 18/33 (54.5%) treated with PCR-B (p=0.08). Of the 28 who achieved a CR/CRi, MRD analysis was completed on 26, of whom 12 (46%) were MRD negative. With respect to treatment arm, 5/32 (16%) patients on PCR and 7/33 (21%) on PCR-B achieved an MRD negative CR.Median time to retreatment for all 65 patients was 44.8 (95% CI: 34.6 – NA) months. Median overall survival has not yet been reached. With current follow-up no differences between treatment-free survival (p=0.38), progression-free survival (p=0.23), or overall survival (p=0.45) are observed by treatment arm.Plasma levels of angiogenic cytokines VEGF, bFGF, thrombospondin (TSP) and the chemokines CCL3 and CCL4 were measured prior to treatment and at the time of the post treatment response evaluation. Correlations of these cytokines with clinical outcome will be presented.CONCLUSION: The addition of bevacizumab to purine analogue-based CIT was generally well-tolerated and may increase complete remission rates in patients with CLL. No clear improvement in treatment free survival has been observed to date. DisclosuresShanafelt:Hospiria: Research Funding; Pharmacyclics/Jannsen: Research Funding; Cephalon: Research Funding; Celgene: Research Funding; glaxoSmithKline: Research Funding; Genetech: Research Funding; Polyphenon E Int’l: Research Funding. Off Label Use: Off label use of pentostatin for treatment of CLL. Off label use of bevacizumab for treatment of CLL. . Kay:Genetech: Research Funding; Pharmacyclics: Research Funding; Hospira: Research Funding; Celgene: Membership on an entity’s Board of Directors or advisory committees; Gilead: Membership on an entity’s Board of Directors or advisory committees.

Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Accuracy of MRI, mammography (MG), and 2D and 3D ultrasound (2DUS/3DUS) in determining the pathologic tumor response after neoadjuvant chemotherapy (NACT) in breast cancer patients.

1067 Background: The pathological tumor response in patients with locally advanced breast cancer to NACT is essential for survival and for surgical strategies. Therapy monitoring based on German recommendations is routinely performed by clinical examination, MG and 2DUS. The clinical value of MRI and 3DUS has not been established yet. The aim of the study was to determine the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) between the different imaging techniques in predicting postoperative histological tumor response after NACT. Methods: Patients with primary breast cancer (cT1-T4, cN0-1, M0) undergoing neoadjuvant chemotherapy between 2005 and 2010 were eligible for this prospective trial. The response was measured by MRI, MG, 2DUS and 3DUS for complete or partial remission versus stable disease after the last cycle of treatment and compared with the final pathological response. Patients with progressive disease were excluded from the study. Statistical analysis was done by calculating the accuracy of each imaging technique and the size difference between imaging and histological tumor size. Sensitivity, specificity, PPV and NPV were calculated for complete or partial pathological response. The study was approved by the local ethic committee (BCD001 194/2004). Results: 103 patients with the mean age of 47.7 (range 24.5 – 71.4) years were evaluated. The accuracy was 0.680 (95%CI: 0.580 -0.768) for MRI, 0.563 (95%CI: 0.453-0.669) for MG, 0.724 (95%CI: 0.618 -0.815) for 2DUS and 0.710 (95%CI: 0.588-0.813) for 3DUS. Sensitivity, specificity, PPV and NPV were 78%, 47%, 75% and 52% for MRI, 61%, 45%, 69% and 36% for MG, 93%, 23%, 74% and 60% for 2DUS, 94%, 19%, 73% and 57% for 3DUS. The mean (standard deviation) size difference was -1.8 mm (14.8) on MRI, 1.5 mm (26.0) on MG, -9.1mm (19.1) on 2DUS and for the volume difference -6916mm3 (15831) on 3DUS. Conclusions: The data suggest that 2DUS is sufficient in predicting tumor response between NACT treatment. MRI and MG are more accurate the 2DUS in predicting the tumor size for surgical planning.

Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses

Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and, by measuring organ damage and tumor stage, can influence treatment. Moreover, elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma. We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, and bilirubin; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment. Patients (n=602) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase (not significantly elevated, mildly elevated, or moderately elevated), alpha-fetoprotein (normal or elevated), and bilirubin (normal or elevated). Bilirubin was measured at baseline and on day 1 of each cycle. Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin had shorter overall survival (OS) than those with normal baseline concentrations, irrespective of treatment group. No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin. Median changes from baseline in bilirubin concentration at the last cycle of treatment were +0.17 and +0.19 mg/dl in the sorafenib and placebo groups, respectively. These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma, irrespective of baseline alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy.

Relevance of monitoring metabolic reduction in patients with relapsed or refractory follicular and mantle cell lymphoma receiving bendamustine: a multicenter study

The aim of the present study was to investigate the relevance of monitoring metabolic reduction evaluated by (18) F-fluorodeoxyglucose ((18) F-FDG) PET/CT in relapsed or refractory patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) who received bendamustine. We conducted a phantom study of 18F-FDG PET/CT to ensure quality control for performing a multicenter clinical study. We analyzed 49 patients with relapsed or refractory FL and MCL who received bendamustine (120 mg/m(2)) on days 1-2 of a 21-day cycle for up to six cycles as a licensing phase II study. 18F-FDG PET/CT scans were acquired before the first and after the last cycle. In a total of 175 target lesions, the maximum perpendicular diameter (Max PD), minimum PD (Min PD), sum of the products of the Max PD (SPD), maximum standardized uptake value (SUVmax), and the percentage reduction rates of Max PD (%Max PD), SPD (%SPD) and SUVmax (%SUVmax) were evaluated for the response to treatment. The therapeutic response was assessed after the last cycle of treatment according to the revised response criteria for malignant lymphoma (revised RC). We evaluated 134 lesions in 39 patients (76%) achieving complete response (CR) and 41 lesions in 10 patients (24%) not achieving CR. The Max PD, Min PD, SPD and SUVmax of the lesions after the last cycle were significantly higher in patients with non-CR than in patients with CR. The %MPD, %SPD and %SUVmax of the lesions were significantly greater in patients with CR than in patients with non-CR (P < 0.0001). Metabolic reduction was observed in all target lesions of relapsed or refractory patients with FL and MCL who achieved CR after bendamustine therapy.

Diffuse large B-cell non-Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Diffuse large B-cell non-Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Palliation of Pelvic and Head and Neck Cancer with Paclitaxel and a Novel Radiotherapy Regimen

In patients with advanced malignancies, local palliation is undertaken if the patient is not a candidate for aggressive intervention. We developed a prospective study using the same radiotherapy schedule as the Radiation Therapy Oncology Group (RTOG) 85-02 with the addition of the radiosensitizer paclitaxel to evaluate its effect on the tumor response rate, palliation of symptoms, and toxicity. Twenty subjects with advanced pelvic or head and neck cancer were enrolled after signing an informed consent. Paclitaxel 60 mg/m(2) was administered 1 hour prior to the first day of each radiation cycle. Radiation therapy was delivered in 2 daily fractions of 3.7 Gy for 2 days every 3 weeks for three cycles (total dose 44.4 Gy). This radiotherapy schedule is referred to as "Quad Shot'' at our institution. Nineteen patients had adequate follow-up data and were considered evaluable. Five patients had a complete response (CR) and 13 patients had a partial response (PR) with symptomatic improvement for a response rate of 94.7%. One patient only had a minimal response. Seventeen patients (89.5%) had palliation of their presenting symptom(s). Eight patients had effective palliative benefit lasting more than 6 months. Two patients experienced a grade 2 allergic reaction to paclitaxel, one of them received the last cycle of treatment with cisplatin obtaining a CR. No late toxicities have been observed. This palliative schedule has been shown to provide good tumor response and palliation of symptoms. The toxicity profile remains low with the addition of paclitaxel. Further investigation is warranted in a larger trial. Palliation of symptoms resulted in improved quality of life for this group of patients.

Age and homocysteine plasma levels are risk factors for thrombotic complications after ovarian stimulation.

The magnitude of thrombotic risk during ovarian stimulation cycles is not known. We calculated the magnitude of thrombotic risk in a cohort of women starting a new cycle of ovarian stimulation and investigated the role of inherited and acquired thrombophilia for these events. This is an observational study involving outpatients of a clinical research centre. Consecutive women undergoing ovarian stimulation (n = 305) were enrolled. Blood samples for studying inherited and acquired thrombophilia were obtained > or = 2 months after the last cycle of treatment. Odds ratios (OR) and confidence intervals (CI) were determined for markers significantly associated with thrombotic events. Blood samples were analysed for inherited and acquired causes of thrombophilia (antithrombin, protein C, protein S, antiphospholipid antibodies, the Factor V Leiden and FIIA20210 mutations, the TT677 MTHFR genotype, and homocysteine plasma levels). Thrombotic events were observed in 4/747 cycles of ovarian stimulation, with a prevalence of 0.5%, corresponding to 1.6 per 100 000 cycles/woman. Age > or = 39 years and homocysteine plasma levels above the 97.5 percentile were significantly associated with thrombotic events during IVF [OR 15.2 (95% CI 2.0-115.0) and 14.4 (1.5-141.3) respectively]. Age > or = 39 years and mild hyperhomocysteinaemia are strongly associated with the occurrence of thrombotic events during IVF.

Response of Resistant Idiopathic Thrombocytopenic Purpura to Pulsed High-Dose Dexamethasone Therapy

Most patients with chronic idiopathic thrombocytopenic purpura have a response to corticosteroids or intravenous immune globulin, but improvement is often transitory. Splenectomy may provide only a short-term benefit. Because pulsed high-dose therapy with potent synthetic corticosteroids is inexpensive, well tolerated, and effective in patients with secretory B-cell neoplasms, a similar regimen was examined for its efficacy in patients with chronic idiopathic thrombocytopenic purpura that was resistant to other treatments. Ten consecutively referred patients who had persistent symptomatic idiopathic thrombocytopenic purpura after undergoing at least two standard therapies were treated with six cycles of dexamethasone (40 mg per day for 4 sequential days every 28 days). All patients had increased platelet counts (mean [+/- SD] count before treatment, 12,000 +/- 8200 per cubic millimeter; after treatment, 248,000 +/- 130,000 per cubic millimeter). The platelet counts remained above 100,000 per cubic millimeter for at least six months after the last cycle of treatment. There were no serious side effects. Features of hyperadrenocorticism due to prior corticosteroid therapy resolved during treatment. The cost of the drug was approximately $100 per patient. Although the possibility of spontaneous remission and a delayed benefit from prior therapy cannot be excluded in this small group of patients, pulsed high-dose treatment with dexamethasone may provide a low-cost therapeutic option with minimal side effects in patients with refractory idiopathic thrombocytopenic purpura.