Preliminary Results of FDG-PET Scanning after GDP Chemotherapy Prior to Autologous Stem Cell Transplant (ASCT) for Relapsed/Refractory (RR) Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4645-4645
Author(s):  
Matthew D. Cooper ◽  
Umberto Falcone ◽  
Naom Tau ◽  
Eshetu G Atenafu ◽  
Richard Tsang ◽  
...  

Abstract Introduction: Gemcitabine, dexamethasone and cisplatin (GDP) has become a standard salvage chemotherapy (SC) regimen for relapsed/refractory (RR) lymphoma prior to autologous stem cell transplantation (ASCT) (Crump JCO 2014). Response to SC is now evaluated using 18-Fluoro-deoxyglucose positron-emission-tomography (FDG-PET) scans based on the recent Lugano classification (Cheson JCO 2014). We evaluated the response of patients (pts) with Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL) to GDP by PET-CT scans and attempted to determine whether PET was predictive of outcome. Methods: We performed a retrospective chart review of consecutive HL and DLBCL (diffuse large B-cell lymphoma) pts who underwent ASCT following GDP SC at our centre between January 2014 and July 2016. All pts previously received anthracycline-based chemotherapy (typically ABVD for HL or R-CHOP for NHL) for primary treatment. Pts underwent FDG-PET scans after 3 cycles of SC and scans were retrospectively reported with the Deauville Criteria Scale with Deauville scores of 1-3 considered negative, whereas scores of 4 or 5 represented a positive result. Response to GDP was documented with CT scans using 1999 Working group Criteria (JCO 1999). Pts proceeded to ASCT if they had a PR by CT imaging and no signs of PD on PET-CT. Post-PET radiation or additional chemotherapy could be given at the discretion of the treating physician. Progression free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method from the date of progression or date of ASCT. Statistical analysis to determine the significance of PET result on outcome was performed using the long rank test. Results: 45 pts with DLBCL and 29 pts with HL were identified: median age was 45 (range: 23-69) and 29 (range: 19-58) years respectively. Baseline patient characteristics are listed in Table 1. Following GDP SC, PET Deauville scores of 1-3 were reported in 55% of HL and 29% of DLBCL pts. Overall response rate to GDP by CT was 72% for HL pts and 64% for DLBCL pts (Table 2). For HL, 100% (16/16) of pts with a PET(-) scan and 91% (10/11) with a PET(+) result proceeded to ASCT. 85% (11/13) of DLBCL pts who had a PET(-) scan and 48% (15/31) with a PET(+) scan underwent ASCT. Additional therapy post PET scan included involved field radiation, additional chemotherapy (mini-BEAM) or novel therapy (brentuximab and bendamustine for HL patients). Median follow-up time was 14.2 months (HL) and 13.4 months (DLBCL) from relapse/progression after initial chemotherapy; and 9.6 months (HL) and 10.9 months (DLBCL) from ASCT. There was a statistically significant difference between PET(+) and PET(-) DLBCL patients from the time of initial disease progression for PFS (26% versus 69%, p=0.011) that did not reach statistical significance for OS (p=0.072). However, there was no significant difference for PFS and OS in DLCBL from ASCT when stratified by PET result (p= 0.154 and p=0.723 respectively). In HL pts, no statistically significant differences for PFS and OS from progression (p=0.480 and p=0.387 respectively) or from ASCT (p=0.579 and p=0.450 respectively) were found when stratified by PET result (see Tables 3 and 4). Conclusion: Deauville 4-5 PET scores appear to be predictive of PFS for RR-DLBCL pts. The lack of a significant difference between PET results for OS in DLBCL is likely due to sample size and the need for longer follow-up. For RR-HL pts, PFS and OS rates were both high but did not seem to noticeably differ by PET result. Additional therapy employed for Deauville 4-5 patients peri-ASCT could influence outcome. Overall, PET response assessment post GDP appears to stratify outcome in patients with DLBCL and PET adapted therapy in HL patients may improve outcome in Deauville 4-5 patients. Review of pending cases and subsequent follow-up is ongoing. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2180-2180
Author(s):  
Jeanne Palmer ◽  
Timothy Goggins ◽  
Gloria Broadwater ◽  
Nelson J. Chao ◽  
John Chute ◽  
...  

Abstract This study was designed to investigate the predictive value of early pre/post stem cell transplant (SCT) FDG-PET on outcomes in non hodgkins (NHL) or Hodgkins lymphoma (HL). We analyzed patients who received SCT for treatment of relapsed or refractory NHL or HL at Duke Medical Center between the years of 1996–2007. Patients who had either a FDG-PET scan following salvage chemo- or radio- therapy and within 14 weeks of transplantation (pre-PET)or a FDG PET scan within 6–14 weeks following transplantation (post-PET) were included in the analysis. PET was determined to be positive or negative based on chart review of radiology reports. Survival times are estimated using Kaplan- Meier method. Hazard ratios (HR) are from univariate Cox proportional hazards models. Overall survival (OS) was measured from the time of transplant until death, and for those patients still alive, it was censored at the last follow up date. Disease free survival (DFS) was measured from the time of transplant until first progression or death, whichever occurred first, and was censored at the date of last follow up for those alive without progression. A total of 102 patients were identified with PET in the appropriate time period. Median age was 48.5 (18–78); 71 patients had NHL, 31 patients had HL. Ninety-eight (96%) of the patients had chemosensitive disease, and had a documented PR (62) or CR (36) prior to transplant. The median DFS and OS of this population was 55 and 73 mo respectively. Median time to follow up was 38 mo (1.5 – 145 mo). Of the 75 pre-PET scans, 32 (43%) were positive; of the 78 post-PET scans, 22 (28%) were positive. At the time of this analysis, 28 (27%) of the patients had died from disease progression. There were 8 (10.6%) pre-PET, and 7 (9%) post- PET readings that were not clear. Our analysis revealed that neither pre-PET nor post-PET results were predictive of DFS (HR 1.73 p=0.16, HR 1.97 p = 0.052) or OS (HR 1.92 p=0.13; HR1.65 p=0.21). Further, for the patients who had measurable disease at the entry to SCT, post-PET was not predictive for DFS (HR 1.62, p=0.29) or OS (HR 1.59 p=0.35). Exclusion of unclear PET readings did not have any effect on these results. In subset analysis, post- PET did predict DFS in patients with NHL (HR 2.6 p=0.034). Our results suggest that early pre/post SCT PET analysis is not beneficial in this algorithm for predicting overall survival in these patients. Negative post-PET may predict DFS in patients with aggressive NHL, however, did not predict OS in this group. Our analysis indicates that other methods of determining risk of relapse and transplant outcome are needed.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Luisa Fernanda Sánchez-Valledor ◽  
Thomas M. Habermann ◽  
Iván Murrieta-Álvarez ◽  
Andrés A. León-Peña ◽  
Yahveth Cantero-Fortiz ◽  
...  

Background: Hodgkin's lymphoma (HL) is the model of curative care with radiation therapy, combination chemotherapy, staging approaches, peripheral blood stem cell transplantation, and immunotherapy. However, the value of the novel anti cancer drugs has been recently analyzed and questioned in view of the results in the real improvement of overall survival (OS). Material and methods: All consecutive patients seeking medical care after 1986 in our institution as a result of HL and followed for at least 3 months were entered in the study. A diagnosis of HL was based on the histological study of a pathology specimen, mainly a lymph node; the same pathologist analyzed all the specimens and defined the histological subtype. Clinical stage was defined according to the Ann Arbor classification. Bone marrow biopsies were done only in patients with clinical stages III or IV. Computed tomography (CT) scans were done in all cases, prior to starting the treatment. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans were performed since 2002. Between 1986 and 1997, patients were treated with MOPP, and after 1997 with ABVD as frontline therapy. For stages I and II, four cycles of chemotherapy were delivered and a computerized tomography (CT) scan was performed; if lymph node enlargement were present at this point in time, four additional cycles were given, whereas two additional cycles were given if the CT scan was negative. For stages III and IV, the CT scans were performed at the end of six cycles and two or four more cycles. Mediastinal radiotherapy was delivered only to persons with a positive FDG-PET scan at the end of the treatment. Patients showing activity after these treatments were considered as refractory and treated with four courses of ICE (ifosfamide, carboplatin and etoposide). Autologous or allogeneic peripheral blood hematopoietic stem cell transplants (HSCT) were given to refractory patients after achieving a complete remission (CR): High-dose melphalan (200mg/m2) was employed in autologous transplants, whereas cyclophosphamide, fludarabine and busulfan were employed in allogeneic transplants, all of them from HLA-identical siblings. After the completion of the treatment, patients were every two months for one year and every four months later on. No FDG-PET scans were done during the follow up, unless clinically indicated. Results: Among 91 patients with HL identified between 1986 and 2020, 88 were followed three months or more and were included in the analysis. There were 37 females and 51 males. The median age was 29years (range5-73years). There were 62 patients with nodular sclerosing HL (70%), 19 mixed cellularity (HL), 2 lymphocyte depleted HL, and one lymphocyte predominant HL; in 4 cases the histologic variant could not be defined. According to Ann Arbor classification, 5 patients were found in stage I, 48 in stage II, 19 in stage III and 16 in stage IV. Ten patients presented with a mediastinal mass larger than 10 cm. in the chest X-ray film. Three cases presented with relapsed disease. Patients have been followed for a median of 114 months (range4-402). 44 patients are alive, 10 have died and 34 were lost to follow-up. Median OS for all the patients has not been reached, being above 402 months, the OS at 310 months is 88% and at 402 months 77%. Median OS has not been reached and is above 94, 109, 90 and 98 months for stages I, II, III and IV, respectively (p=0.2). The 310-month OS was 83% for patients treated with MOPP and 88% for those treated with ABVD (HR:0.76, 95% CI 0.2-2.8; p=0.6).Sixteen patients (18%) were refractory to the treatment and 9 (10%) relapsed; they were treated with ICE followed by HSCT (autologous 15 patients and allogeneic 10 patients). Patients who underwent auto-HSCT had a median survival of 329.1 months and an OS of 92.3%, whereas those given allo-HSCT had a median survival of 59.3 months and an OS of 45.7% (HR0.2, 95%CI 0.04-1.3, p=0.057). The OS of patients given or not HSCT was 73.5% and 92.9% at 266 and 404 months, respectively (HR4.09, 95%CI 1.0-16.6, p=0.01). The OS was similar. The causes of death were breast carcinoma in 2 cases, liver carcinoma in one and uncontrolled lymphoma activity in the remaining. Conclusion: HL may be less aggressive in Mexican population than in Caucasians. Combined chemotherapy renders acceptable results, irrespective of clinical stage. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 20 ◽  
pp. 153303382110246
Author(s):  
Seokmo Lee ◽  
Yunseon Choi ◽  
Geumju Park ◽  
Sunmi Jo ◽  
Sun Seong Lee ◽  
...  

Background and Aims: This study evaluated the prognostic value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) performed before and after concurrent chemoradiotherapy (CCRT) in esophageal cancer. Methods: We analyzed the prognosis of 50 non-metastatic squamous cell esophageal cancer (T1-4N0-2) patients who underwent CCRT with curative intent at Inje University Busan Paik Hospital and Haeundae Paik Hospital from 2009 to 2019. Median total radiation dose was 54 Gy (range 34-66 Gy). Our aim was to investigate the relationship between PET/CT values and prognosis. The primary end point was progression-free survival (PFS). Results: The median follow-up period was 9.9 months (range 1.7-85.7). Median baseline maximum standard uptake value (SUVmax) was 14.2 (range 3.2-27.7). After treatment, 29 patients (58%) showed disease progression. The 3-year PFS and overall survival (OS) were 24.2% and 54.5%, respectively. PFS was significantly lower ( P = 0.015) when SUVmax of initial PET/CT exceeded 10 (n = 22). However, OS did not reach a significant difference based on maximum SUV ( P = 0.282). Small metabolic tumor volume (≤14.1) was related with good PFS ( P = 0.002) and OS ( P = 0.001). Small total lesion of glycolysis (≤107.3) also had a significant good prognostic effect on PFS ( P = 0.009) and OS ( P = 0.025). In a subgroup analysis of 18 patients with follow-up PET/CT, the patients with SUV max ≤3.5 in follow-up PET/CT showed longer PFS ( P = 0.028) than those with a maximum SUV >3.5. Conclusion: Maximum SUV of PET/CT is useful in predicting prognosis of esophageal cancer patients treated with CCRT. Efforts to find more effective treatments for patients at high risk of progression are still warranted.


2016 ◽  
Vol 37 (6) ◽  
pp. 602-608
Author(s):  
Mehdi Taghipour ◽  
Sara Sheikhbahaei ◽  
Tyler J. Trahan ◽  
Rathan M. Subramaniam

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2330-2330 ◽  
Author(s):  
Rebecca L. Elstrom ◽  
Richard K.J. Brown

Abstract Background and Objectives: Positron tomission tomography using 18fluoro-2-deoxyglucose in combination with low dose non-enhanced computed tomography (FDG-PET/CT) is increasingly utilized in the management of patients with lymphoma. Numerous studies have demonstrated improved accuracy for both staging and restaging as compared to standard diagnostic CT. However, there is a paucity of data on the significance of bone uptake in patients with lymphoma. This is one area in which FDG-PET has the potential to dramatically influence care of lymphoma patients. However, false positive FDG-PET has been shown in patients with traumatic or benign bone lesions. The aim of this study was to evaluate the utility and accuracy of FDG-PET/CT in comparison with standard anatomic imaging with CT and MRI in the staging and follow up of patients with Hodgkin lymphoma (HL) or diffuse large B cell lymphoma (DLBCL). Design and Methods: We reviewed a database of 75 lymphoma patients who underwent concurrent FDG-PET/CT and standard diagnostic CT scans or MRI, and identified those with bone involvement by lymphoma. Involvement of bone was demonstrated by either biopsy of a bone lesion or radiologic appearance and clinical follow up highly suggestive of bone involvement. Follow up studies were evaluated for resolution of FDG avid lesions on PET, and anatomic lesions on CT or MRI. Results: Fourteen patients with either HL or DLBCL who underwent both FDG-PET/CT and diagnostic CT were identified to have bone involvement by lymphoma. FDG-PET identified bone involvement in all 14 patients, whereas CT imaging identified bone involvement in seven. One patient in whom CT did not detect bone involvement had evidence of bone lymphoma by MRI. Eight patients had confirmation of bone lymphoma by biopsy, while 6 were confirmed by clinical criteria (radiologic appearance and clinical follow up). Thirteen of the patients had follow up FDG-PET/CT scans, and 12 had follow up CT and/or MRI. All follow up FDG-PET scans showed resolution of FDG avid bone lesions after anti-lymphoma therapy. In contrast, all CT and MRI scans which originally showed evidence of bone involvement had persistent abnormality on follow up, with only 2 showing improvement. At a median follow up of 9 months (range 0–20 months), 11 patients remain in remission, while 2 patients subsequently showed progression by FDG-PET, CT and biopsy in soft tissue sites, but not bone. One patient remains on therapy. No patient in our series was found to have a benign etiology of a lesion initially thought due to lymphoma. Conclusion: FDG-PET/CT is useful in the staging and follow up of patients with lymphoma with bone involvement. The lack of sensitivity of CT combined with the delayed resolution of anatomic abnormalities limit the utility of standard anatomic imaging, making FDG-PET/CT the imaging modality of choice for patients with bone lymphoma.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1937-1937
Author(s):  
Xavier Leleu ◽  
Renee Leduc ◽  
Meghan Rourke ◽  
Brianna Harris ◽  
Aldo M. Roccaro ◽  
...  

Abstract Abstract 1937 Poster Board I-960 Background. Waldenstrom's macroglobulinemia is a rare B cell neoplasm characterized by the production of a monoclonal IgM protein and a lymphoplasmacytic infiltrate in the bone marrow. The clinical manifestations related to tumor infiltration include hepatomegaly (20%), splenomegaly (15%) and lymphadenopathy (15%). Organomegaly was associated with adverse prognosis in a large series of WM. More sensitive tools of tumor burden and prognosis are needed in these patients. The use of FDG-PET has not been previously studied in WM but has proved an effective diagnostic and prognostic tool in other in low-grade lymphomas. Therefore the objective of this study was to determine whether FDG-PET was an effective tool in evaluating pts with WM. Methods. We prospectively studied PET/CT in 39 WM patients homogeneously treated with bortezomib-rituximab (given IV bortezomib 1.6mg/m2 at days 1, 8, 15 q 28 days × 6 cycles and rituxan 375 mg/m2 at days 1, 8, 15, 22 on cycles 1 and 4) on a phase II clinical trial, at diagnosis (N=12) and with relapsed/refractory disease (N=27). All pts underwent staging evaluation by FDG-PET in combination with CT scan before and after therapy. PET results were analyzed as positive or negative. Response (ORR) was assessed after cycle 3, confirmed with 2 consecutive values and included minor response or better. Overall (OS) and treatment free survivals (TFS) were calculated from start of treatment to date of last follow up and time of next treatment, respectively. Results. The median age of the population was 62 years (range, 43-78), Male/Female ratio 1.64, WM-International staging score breakdown was 46% low, 23% intermediate, 31% high. Serum M-spike was 2.5g/L (0.41-4.62) with 8% patients >= 4g/L. The overall response rate was 89.7% with minor response in 13 pts and major response in 22 pts. With a median (+/-se) follow-up of 15 months (+/-1.22), death occurred in 2 patients, and the median OS was not reached with a 3-year probability of survival of 89%. The median TFS was 21 months (+/-2.09). Twenty-five (64.1%) and 13 (37.1%) patients had a positive PET before and after treatment, respectively. 11 (45.8%) patients had a negative post treatment PET which was positive before treatment, 1 (4.8%) had a positive PET after treatment while initially negative and all other patients had no change. Patients with positive PET before treatment had no clinical-biological difference (age, gender, hemoglobin level, serum beta 2-microglobulin value, platelet count, IgM spike and ISS-WM score) with other patients. A positive PET before treatment had no influence on either OS or TFS or ORR or MR. However, a normal PET after treatment, including a negative PET after treatment which initially was positive before treatment, correlated with response (p=0.04). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for a normal PET after treatment and for a negative PET after treatment while initially positive before treatment in predicting ORR were 68.7%, 100%, 100%, 23% and 52.4%, 100%, 100%, 23.1%, respectively. Although the number of deaths is low in this series, a positive PET after treatment was an adverse prognostic factor for OS. The median survival and the 2-year probability of survival was not reached and 100% for patients with a normal (negative) PET after treatment (number of death/number of pts in the group, O/N=0/22) while it was 20 months and 46% for patients with a positive PET after treatment (O/N=2/13 ), respectively (p=0.019). Conclusion: Over 60% of WM pts demonstrated FDG-avid disease when using FDG-PET scans with the majority showing negative imaging after therapy. PET positive scans after therapy correlated with poor prognosis. FDG-PET scans may prove an effective tool in the diagnosis and prognosis in WM. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 8 ◽  
Author(s):  
Brian K. Flesner ◽  
Bryan T. Torres ◽  
Kyle D. Hutcheson ◽  
Hansjörg Rindt ◽  
Amy R. Zalcman ◽  
...  

Cancer-induced bone pain, despite its frequency and severity, is a poorly understood phenomenon in people and animals. Despite excitement regarding translational osteosarcoma studies, there is a lack of attention toward examining cancer pain in dogs. In this pilot study, we used a multimodal pain assessment methodology to evaluate pain relief after therapeutic intervention in dogs with primary bone cancer. We hypothesized that intervention would cause objective evidence of pain relief. Evaluations of 8 dogs with primary bone cancer included 18F-FDG PET/CT scans, kinetic analysis, validated owner questionnaires (Canine Brief Pain Inventory, canine BPI), and serum N-telopeptide (NTx) concentration. Dogs were routinely staged and had 18F-FDG PET/CT scans prior to treatment with day 0, 7, 14, and 28 canine BPI, serum NTx, orthopedic exam, and kinetic analysis. Dogs treated with zoledronate and radiation underwent day 28 18F-FDG PET scans. All clinical trial work was approved by the University of Missouri IACUC. Four dogs underwent amputation (AMP) for their appendicular bone tumors; four received neoadjuvant zoledronate and hypofractionated radiation therapy (ZOL+RT). Canine BPI revealed significant improvements in pain severity and pain interference scores compared to baseline for all dogs. Positive changes in peak vertical force (+16.7%) and vertical impulse (+29.1%) were noted at day 28 in ZOL+RT dogs. Dogs receiving ZOL+RT had a significant (at least 30%) reduction in serum NTx from baseline compared to amputated dogs (p = 0.029). SUVmax (p = 0.11) and intensity (p = 0.013) values from PET scans decreased while tumor uniformity (p = 0.017) significantly increased in ZOL+RT-treated tumors; gross tumor volume did not change (p = 0.78). Owner questionnaires, kinetic analysis, and 18F-FDG PET/CT scans showed improved pain relief in dogs receiving ZOL+RT. Serum NTx levels likely do not directly measure pain, but rather the degree of systemic osteoclastic activity. Larger, prospective studies are warranted to identify the ideal objective indicator of pain relief; however, use of multiple assessors is presumably best. With improved assessment of pain severity and relief in dogs with cancer, we can better evaluate the efficacy of our interventions. This could directly benefit people with cancer pain, potentially decreasing the amount of subtherapeutic novel drugs entering human clinical trials.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 137-137 ◽  
Author(s):  
Ivana N. Micallef ◽  
Matthew J. Maurer ◽  
Thomas E. Witzig ◽  
Daniel Nikcevich ◽  
Paul Kurtin ◽  
...  

Abstract Abstract 137 Background: FDG-PET/CT after 2–4 cycles of chemotherapy has been shown to be predictive of outcome in patients with aggressive lymphoma. This multicenter NCCTG phase II study was carried out to assess efficacy of ER-CHOP in newly diagnosed DLBCL; functional response as measured by FDG-PET/CT was done after 2 cycles and after 6 cycles of therapy. Methods: Patients received immunochemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard dose CHOP every 3 weeks for 6 cycles. FDG-PET/CT was done after 2 cycles and again after 6 cycles of therapy. All PET scans were centrally reviewed by an expert in nuclear medicine who was blinded to the outcome of the patients. Results: 107 patients were accrued from Feb 2006 to Aug 2007. 27 patients were ineligible resulting in 80 eligible patients. Baseline patient characteristics for the eligible patients included median age 60 (range 21–82); 56% were male. 80% had advanced stage; 73% had an elevated LDH. Performance score was 0–1 in 71 pts and 2–3 in 9 pts. IPI was 0–1 in 18 pts (23%), 2 in 22 pts (28%), 3 in 29 pts (36%) and 4–5 in 11 pts (14%). PET scans were available on 76 patients (95%); 3 patients completed treatment but scans were unavailable and 1 died prior to cycle 2 PET. The PET CR rate after 2 cycles was 79%. The PET CR rate after 6 cycles was 90%. Using an intent to treat (ITT) analysis, 67 patients (87%) achieved PET CR of which 61 (79%) also completed all 6 cycles of treatment. Based on interim PET after 2 cycles, the EFS at 24 months (EFS24) was 73% for the PET negative patients vs 60% for the PET positive patients (p=0.25); OS at 24 months (OS24) was 83% vs 73% for the PET negative and positive pts, respectively (p=0.17). In comparison, EFS24 for patients with a negative PET after 6 cycles was 80% vs 57% for those with a positive PET (p=0.11); OS24 was 92% vs 57%, respectively (p=0.01). In intent to treat (ITT) analysis, patients that achieved a functional CR had improved overall survival (OS24 = 84%) and event free survival (EFS24 = 74%) compared to patients that failed to achieve a functional CR (OS24 = 50%, EFS24 = 40%, p=0.01 and p=0.006 respectively). Conclusions: ER-CHOP every 21 days × 6 cycles results in a functional CR rate of 87%. Early PET scan during therapy does not significantly predict outcome. Achievement of PET negativity by completion of therapy is associated with a good outcome Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3414-3414
Author(s):  
Douglas A. Stewart ◽  
Peter Duggan ◽  
Nizar J Bahlis ◽  
Andrew Daly ◽  
Michelle Geddes ◽  
...  

Abstract Abstract 3414 Poster Board III-302 Purpose Approximately 50-55% of patients (pts) with stage 3-4 DLBCL and elevated serum LDH achieve long-term event-free survival (EFS) following R-CHOP chemotherapy. A prospective, multicentre, phase II clinical trial was designed to evaluate the use of high dose sequential therapy with RDICEP then RBEAM/ASCT for such pts who have positive interim restaging FDG-PET/CT scans after 2 cycles of RCHOP. Patients and Methods Pts were eligible if they were HIV-, 18-65 years of age, and had stage 3-4 DLBCL with elevated serum LDH. An FDG-PET/CT scan was performed 10-15 days following the second cycle of R-CHOP. Pts with negative interim restaging PET scans completed 4 further cycles of RCHOP, whereas pts with positive PET scans (more than 1 site with uptake more intense than background liver) received one cycle of RDICEP (Rituximab 375mg/m2 day 1 and 8, C 1.75g/m2 d2-4, E 350mg/m2 d2-4 P 35mg/m2 d2-4, G-CSF d15-21 and autologous blood stem cell collection by apheresis d21or 22) followed by one cycle of RBEAM/ASCT (Rituximab 375mg/m2 day -6 and +14, BCNU 300mg/m2 d-6, E 200mg/m2 d-5to-2, A 400mg/m2 d-5to-2, M 140mg/m2 d-1). Results Of the 36 pts who have been accrued from 5/2007-7/2009, 33 pts have undergone interim PET/CT restaging following 2 cycles RCHOP. All 33 pts had IPI scores 3-5, the median age was 55 years (range19-65) with 7 pts (21%) older than 60 years, 20 (61%) had ECOG status 2-4, 28 (85%) had stage 4, 22 (67%) >1 extranodal site. At a median follow-up of 12mo, the 1 year OS and EFS rates for all 33 pts are 82% (95%CI = 66-98%) and 76% (95%CI = 58-83%), respectively. Interim restaging PET/CT was positive for 16 pts and negative for 17 pts. The EFS rates for PET+ and PET- pts are 78% (95%CI = 57-100%) and 66% (95%CI = 36-99%), respectively (logrank p=0.97). To date, 4 pts have died, 3 from lymphoma at 6, 10, 11 months post-RCHOP1, and 1 from sepsis and necrotic bowel on day 5 post-ASCT. Conclusions Preliminary results of this phase II study are encouraging, and suggest that high dose induction therapy with RDICEP and RBEAM/ASCT might improve EFS for poor prognosis DLBCL with positive interim restaging PET/CT. Accrual will continue to target ≥ 35 PET+ and ≥35 PET- pts. Disclosures Stewart: Hoffmann La Roche: Advisory Board, Honoraria, Research Funding. Off Label Use: Rituximab with High Dose Chemotherapy and Autologous Stem Cell Transplantation for DLBCL. Bence-Bruckler:Hoffmann La Roche: Honoraria, Research Funding.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 855-855 ◽  
Author(s):  
Judith Trotman ◽  
Marion Fournier ◽  
Thierry Lamy ◽  
Jane A Estell ◽  
Anne Sonet ◽  
...  

Abstract Abstract 855 Aim: Despite its often indolent clinical course, follicular lymphoma (FL) is a heterogeneous disease. Current criteria for early identification of patients with a poor prognosis are suboptimal - the FLIPI and F2 index are insufficient prognostic markers for individual patients and the limitations of post-treatment conventional response criteria have long been acknowledged. FL shows increased FDG uptake, but unlike DLBCL, minimal data exist about the role of PET-CT in response assessment. We have used the prospective conventional response assessment and 42 month patient follow-up in the PRIMA (Primary Rituximab and Maintenance, Salles et al., ASCO 2010, Abstr#8004) study as a platform for analysis of the utility of PET-CT in FL. Methods: The PRIMA database was interrogated and investigators surveyed to identify PET-CT scans performed during staging and induction response assessment. Single modality PET-only scans were not eligible for inclusion. Local PET interpretation (positive + or negative -) was used to explore associations with patient outcomes. The primary endpoint was PFS from PRIMA registration. Results: 277 PET-CT scans on 160 patients from 40 centres were identified. Baseline patient characteristics did not differ from the overall PRIMA patient population. Positive PET-CT scans were recorded in 119/120 (99%) at diagnosis, 11/33 (33%) interim restaging scans and 32/124 (26%) post induction treatment (R-CHOP or R-CVP). There was significant correlation between PET-CT result and conventional response assessment at the end of immunochemotherapy (p<0.0005). The incidence of post-treatment PET+ increased across the categories of lesser conventional responses, occurring in 8% (4/50) CR, 31% (12/39) CRu, 41% (11/37) PR, 67% (2/3) SD, and 80% (4/5) PD. While 73/91 (80%) of PET- patients were in CR/CRu, given the very high overall response rate on study, 16/33 (48%) of the PET+ population were also in CR/CRu. With a median follow-up of 42 months, a significantly inferior actuarial 3yr PFS was observed in post-treatment PET+ vs. PET- patients (Figure 1): 32% (95% CI 17–48%) vs. 74% (95% CI 63–82%) (log rank p<0.0001, HR 3.5, 95% CI 2.0–6.1), median PFS 19 months (13-35) vs. not reached, (52-NR). Using proportional hazard regression analysis, both conventional response (overall p=0.0002) and PET+ status (HR 2.8 p=0.0007) were significant predictors of inferior PFS. However, the predictive power of conventional response assessment was limited to non-responders: SD/PD vs. CR/CRu (HR 6.5, p<0.0001), and SD/PD vs. PR (HR 5.2, p=0.0009). Comparison of PR vs. CR/CRu was not different (HR 1.2, p=0.5). While PET+ status had a significant negative impact on PFS in both the CR/CRu (HR 2.6, p=0.015) and PR (HR 4.3 p=0.018) patient groups, there was no difference in outcome between CR/CRu vs. PR patients within the PET+ (HR 1.5 p=0.42) and PET- (HR 1.0 p=0.98) subgroups. When only patients randomised for the maintenance element of the PRIMA study were considered, post-treatment PET+ (15/59) remained predictive of 3yr PFS (27 vs. 69%, HR 3.1, p=0.005) in the observation arm, but post-treatment PET+ (9/47) was not significantly associated with an adverse outcome in patients receiving rituximab maintenance (3-year PFS 56 vs. 81%, HR 2.2, p= 0.18). In a multivariate Cox model including responding patients the following factors were negative predictors of PFS: post-treatment PET+ (HR 3.1 p<0.0014); R-CVP induction therapy (HR 2.8, p<0.014); and baseline β2M ≥3 (HR 2.6 p<0.0042), while conventional PR and FLIPI were not. Conclusion: This PRIMA sub-study demonstrates that post-treatment PET-CT is a powerful predictor of PFS that complements conventional response evaluation after first line immunochemotherapy for FL. Patients who are PET- can expect a prolonged PFS whether in conventional CR or PR, but for those remaining PET+, with a median 19 month PFS, the disease cannot be characterized as indolent. Future clinical trials should evaluate an FDG PET-CT response adapted approach focused on improving outcomes for this group. Disclosures: Seymour: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shpilberg:Roche: Consultancy, Honoraria.


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