ALBERT

Description: Background The ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine) is widely accepted as standard treatment for patients with advanced HL. There are potential long term cardiac and pulmonary toxicites, particularly in combination with mediastinal radiotherapy. The SV regimen comprises brief duration combination chemotherapy, with relatively low cumulative doses of alkylating agents, doxorubicin and bleomycin, followed by consolidation radiotherapy to sites of bulk disease. High response and disease free survival rates are reported in single institution and multi-centre phase II studies. This randomized phase II trial comparing SV with ABVD was designed to determine 1) the feasibility of the SV regimen; 2) response rate compared with ABVD; and 3) acute toxicity of SV. Methods Patients with previously untreated advanced HL were randomised to receive SV chemotherapy for 12 weeks or 6 to 8 cycles of ABVD. All patients with bulky disease (mediastinal disease 〉 1/3 of CTR, nodal masses 〉5cm, macroscopic splenic nodules on CT scan) received involved field radiotherapy (IFRT). ABVD (days 1 & 15: doxorubicin 25mg/m2, bleomycin 10units/m2, vinblastine 6mg/m2, dacarbazine 375mg/m2), q28. SV (mustine 6mg/m2, wks 1,5,9, doxorubicin 25mg/m2, wks 1,3,5,7,9,11, vinblastine 6mg/m2 wks 1,3,5,7,9,11, prednisone 40mg/m2 alternate days, vincristine 1.4mg/m2 wks 2,4,6,8,10,12, bleomycin 5iu/m2 wks 2,4,6,8,10, 12, etoposide 60 mg/m2 wks 3,7,11). Results From Mar 1998 to Jan 2002, 150 (74 SV, 76 ABVD) patients were randomised from 15 UK centers. Pre-treatment characteristics were balanced between the two groups: median (range) age 33 (18–67), male 57%, stage II 43%, III 27%, IV 29%, 76% with B symptoms. 97% SV patients completed 12 weeks treatment, 88% patients received 6 or more cycles of ABVD. In both groups, 75% patients received IFRT. Grade 3 or 4 toxicity was rare. 49% SV and 79% ABVD patients required G-CSF. Overall response rate was 86% in SV and 88% in ABVD. With median follow-up of 42 months, 2-year overall survival was 95%, (95% CI=92%–98%). No treatment related death occurred. Conclusion Stanford V is a potentially less toxic alternative to ABVD. Phase III trial evaluation is underway in the UK.

Description: Background: High-grade transformation (HT) of follicular lymphoma (FL) to diffuse large B-cell lymphoma (DLBCL) occurs at a rate of 3% per year and has been associated with a very poor prognosis, with a median overall survival (OS) of 1 year reported by Montoto et al in the pre-rituximab era. Treatment often includes upfront autologous or allogeneic stem cell transplantation (SCT) due to the poor prognosis, but rarely maintenance rituximab despite evidence in FL. These patients are excluded from the majority of clinical trials and hence the role of SCT in the rituximab era and maintenance rituximab are not well evaluated. Methods: We performed a retrospective analysis of all patients aged ≥18 years with histologically proven transformed follicular lymphoma (TFL) diagnosed and treated (≥1 cycle of chemotherapy) at our institute in the 10-year period 2003-2013. Histopathology databases were searched to identify patients diagnosed with DLBCL and FL (grade 1-3a). Clinical data were collated from electronic patient records. Patients with grade 3b FL were excluded. A minimum interval of 6 months between the diagnosis of FL and development of HT was required for inclusion to outrule a discordant lymphoma. All histological specimens were reviewed by an expert haematopathologist. The study was approved by our institutional review board. Results: Between March 2003 and May 2013, a total of 56 patients were diagnosed with TFL (to DLBCL) and received first-line induction treatment +/- autologous/allogeneic SCT. The median follow-up was 5.6 years. The median time from diagnosis of FL to HT was 5.3 (range 0.6-29.3) years with a median age at diagnosis of TFL of 61 years (range 34-85). 59% (n=33) had received prior chemotherapy for FL. At diagnosis of TFL 89% (n=50/56) of patients received chemotherapy +/- radiotherapy (IFRT) without subsequent SCT. Upfront autologous or allogeneic SCT post induction was performed for 4 (7%) and 2 (3.5%) patients respectively. 91% of patients (n=51/56) received rituximab containing (R) chemotherapy and 68% (n=38/56) were treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). 16.1% (9/56) received IFRT post induction. 14.3% (8/56) patients received R-maintenance following first-line treatment for TFL. For patients treated with R-chemotherapy alone (n=46) the 2 and 5-year OS and PFS (for TFL) were 84.5% and 70.9% and 58.7% and 49.3% respectively. In patients aged 〉65 years (n=17) 5-year OS was similarly 71.6%. Patients treated with R-CHOP had 2 and 5-year OS of 89% and 76% and PFS (TFL) rates of 59.5% and 51.7% respectively. Patients who received R-chemotherapy induction followed by R-maintenance (n=8) had both 2-year OS and PFS (TFL) of 100%. 82% of all patients (46/56) underwent FDG-PET on completion of induction treatment +/- SCT. A negative PET (n=30) was associated with 2 and 5-year OS rates of 90% and 74.1% and PFS (TFL) of 60% and 49.2%. Conclusion: The outcome for TFL has significantly improved with the advent of rituximab. In our analysis the 2 and 5-year OS rates of 84.5% and 70.9% with R-chemotherapy alone are superior to reported OS for patients undergoing upfront autologous/allogeneic SCT, while PFS rates are comparable to those quoted for upfront autologous SCT. Although the numbers are small (n=8) and follow-up shorter, the outcomes for patients treated with R-chemotherapy followed by R-maintenance (2-yr OS and PFS of 100% and 100%) are particularly encouraging while offering minimal additional toxicity. In conclusion our data indicate that upfront SCT may no longer be required for TFL in the rituximab era. Rituximab maintenance should be considered in the management of these patients. Disclosures Hawkes: Roche: Travel grant Other. Peckitt:Sanofi: Membership on an entity's Board of Directors or advisory committees. Dearden:Roche: Membership on an entity's Board of Directors or advisory committees. Cunningham:Astra Zeneca: Research Funding; Novartis: Research Funding; Merck Serono: Research Funding; Sanofi: Research Funding; Celgene: Research Funding; Amgen: Research Funding; Roche: Research Funding.

Description: Introduction: Primary mediastinal B Cell Lymphoma (PMBL) is a high-grade non-hodgkin lymphoma with distinct clinical and biological features. Optimal chemotherapy for this lymphoma is not established but some centres favour more intensive regimes such as DA EPOCH-R over R-CHOP. The role of consolidation radiotherapy is yet to be clarified and whether it can be omitted in those patients with a negative end-of-treatment PET scan (EOT PET) regardless of induction chemotherapy. Furthermore, the occurrence of false positive EOT PET scans may lead to overtreatment. The aim of this study was to establish the outcomes of patients (pts) with PMBL who had been treated in a single centre. Methods: Pts diagnosed with PMBL between 2003 and 2015 in Royal Marsden Hospital were included. Data was collected from electronic patient records and PET CT images review. Survival was defined from date of diagnosis until date of death or date of last follow up. Results: Thirty-four pts were identified with characteristics as shown in the table. Median diameter of the mediastinal mass was 12cm (range 5.5 - 24cm); 25 (74%) pts had a mass of ≥ 10cm. The majority of pts received R-CHOP chemotherapy (2 had 14 day cycles, 30 had 21 day cycles), 1 R-GCVP and another R-PACEBOM. Median number of cycles of chemotherapy was 6 (range 1-8). Seven out of 32 (22%) pts received involved field radiotherapy (IFRT). EOT PET was available for 30 pts. Median time to obtaining EOT PET from completion of chemotherapy was 31 days (20-81). Twenty-three out of 30 pts had EOT PET negative disease with a Deauville score (DS) of 1-3. Twenty-one of these 23 pts did not receive IFRT. Two of these 21 pts relapsed in the mediastinum and were treated with salvage chemotherapy followed by autologous stem cell transplant (ASCT) of whom 1 died due to their lymphoma. The 2 patients who received consolidation radiotherapy remain in remission. Seven out of 30 pts had a positive EOT PET (DS 4-5); of whom 5 received IFRT. Two out of 5 patients relapsed and proceeded with further chemotherapy of whom 1 died due to treatment-related causes while the other 4 patients were alive at time of last follow-up. Two pts with a positive EOT PET did not have IFRT, 1 proceeded with salvage chemotherapy but died due to lymphoma and the other patient was followed up with serial PET scans and ultimately the residual avidity was considered to be due to thymic hyperplasia. Conclusion: Our analysis demonstrates that for the 23 patients who achieved a complete metabolic response on EOT PET the risk of relapse was low (9%) (despite that only 2 patients received consolidation radiotherapy) and only one patient (4%) died of lymphoma. Thus the majority of patients with a negative EOT PET scan following R-CHOP chemotherapy may not need consolidation radiotherapy. This finding should be taken into account when considering the risk/benefit of adding radiotherapy treatment to patients who are already in metabolic CR after chemotherapy. Consolidation radiotherapy is currently being investigated in a prospective IELSG37 trial, NCT01599559. Table. Table. Disclosures Chau: Eli-Lilly: Honoraria, Other: Advisory Board, Research Funding; Bristol Meyers Squibb: Other: Advisory Board; MSD: Other: Advisory Board; Bayer: Other: Advisory Board; Roche: Other: Advisory Board; Merck Serono: Other: Advisory Board, Research Funding; Five Prime Therapeutics: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Janssen-Cilag: Research Funding; Sanofi Oncology: Research Funding. Cunningham:Roche pharmaceuticals: Research Funding.

Description: Introduction: The weekly alternating SV regimen was compared to standard ABVD. An initial randomised phase II pilot study was carried out to determine tolerability and response rate, following which the study was expanded into a phase III trial. Methods: Consenting patients (pts) with advanced HL (bulk disease, B symptoms and/or stage III/IV) were randomised between 6–8 cycles of ABVD or 12 weeks SV, to be followed in both arms by involved field irradiation (34–36Gy) to sites of initial bulk disease (〉5cm) or splenic deposits, and to residual masses. In the phase III study radiotherapy was not required for ABVD pts who achieved complete remission. Drugs given were: ABVD (days 1 & 15): doxorubicin 25mg/m2, bleomycin 10000iu/m2, vinblastine 6mg/m2, dacarbazine 375mg/m2), q28. SV (mustine 6mg/m2, wks 1,5,9, doxorubicin 25mg/m2, wks 1,3,5,7,9,11, vinblastine 6mg/m2 wks 1,3,5,7,9,11, prednisone 40mg/m2 alternate days, vincristine 1.4mg/m2 wks 2,4,6,8,10,12, bleomycin 5000iu/m2 wks 2,4,6,8,10, 12, etoposide 60 mg/m2, 2 consecutive days wks 3,7,11). The primary outcome measure was progression-free survival (PFS). A total of 97 events were required to detect an improvement in 5-year PFS from 75% in ABVD to 85% in SV with a 5% significance level and 80% power. Results: 520 pts were randomized (261 ABVD, 259 SV) between 3/98 and 10/06. Median age was 35. 49% had stage I/II disease with bulk and/or B symptoms, 29% stage III, 22% stage IV. 74% of pts overall had B symptoms and 52% bulk disease. International Prognostic Score (IPS) showed 37% 0–1, 54% 2–3 and 9% 4–7. The treatment groups were well matched for baseline prognostic factors. 95% SV pts completed 12 weeks, and 94% ABVD had 6 (71%) or 7/8 (23%) cycles. Pulmonary toxicity grade III/IV was reported in 37 pts (27 ABVD, 10 SV). More non-pulmonary grade III/IV toxicities were reported in SV(19%) than in ABVD (8%). Radiotherapy was given in 62% overall: 72% SV and 53% ABVD. The overall response rate (CR, CRu, PR) at completion of all treatment was 90% for SV and 89% for ABVD. There was one death due to toxicity on the ABVD arm, and none in SV. With a median 4 years follow up, 113 pts (55 ABVD, 58 SV) had recurrent disease or died with a hazard ratio of 1.10 (95% CI =0.76, 1.59; p=0.61) and 5-year PFS of 76% in ABVD and 74% in SV, absolute difference 2% (95% CI= −5%, 11%). 40 pts died (22 ABVD, 18 SV) with a hazard ratio of 0.81 (95% CI=0.44, 1,52; p=0.51) and 5-year overall survival (OS) of 90% in ABVD and 92% in SV, absolute difference 2% (95% CI -5%, 5%). Pre-planned analysis of sub-groups did not show significant variation in these results according to stage or IPS. Conclusion: There is no evidence of a difference in PFS and OS between SV and ABVD in this trial, which made extensive use of consolidation radiotherapy and included a relatively favourable cohort. More pulmonary toxicity was reported for ABVD, while other toxicities were slightly higher with S V.