Yr Progression-free Survival Research Articles

Primary immunotherapy monotherapy (PRIMO) in locally advanced cutaneous squamous cell carcinoma.

9585 Background: Neoadjuvant immunotherapy is a potential curative approach to patients with locally advanced cutaneous squamous cell carcinoma (cSCC) that offers an attractive alternative to traditional, often morbid surgery and/or radiation. In this study, we report our initial institutional experience treating patients with primary immunotherapy monotherapy (PRIMO) and reserving surgery or radiation for progression only. Methods: Patients with primary or recurrent locally advanced cSCC (AJCC 8 T3-4 or node positive or in-transit metastases) in whom surgical resection and/or definitive radiation were deemed excessively morbid or futile and were treated with PRIMO were included in an IRB-approved database. Patients were treated with IV cemiplimab (350mg q 3week) or pembrolizumab (200mg q3week or 400 q6week). Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) was scored according to iRECIST criteria. Kaplan Meier analysis was used to estimate overall survival (OS) and progression free survival (PFS). Univariate analysis (UVA) for PD was performed using Chi square for categorical variables and Kruskal-Wallis for continuous variables. Results: This study included 36 patients treated between 2017-2023, with a median age of 80 (61-96), and a median follow up of 13.5 months (8-20.5). Most patients had lesions on the head and neck (32; 88.9%), recurrent disease (26; 72.2%), and T3/4N0 disease (20; 55.6%), while 18 patients (50.0%) had nodal disease or in-transit metastases. Cemiplimab was used in 31 patients (86.1%) while pembrolizumab was used for 5 patients (13.9%). Twelve patients (33.3%) stopped PRIMO due to an immune-related adverse event (irAE). 1 and 2yr OS and 1 and 2yr PFS were 76%, 64%, 72% and 51%, respectively. Best initial response to PRIMO was a CR in 15 (41.7%), PR in 14 (38.9%), SD in 3 (8.3%) and PD in 4 (11.1%) patients. All 3 lesions (100%) with SD and 3/14 lesions (21.4%) with PR ultimately progressed with a median duration of response of only 3 months (2.0-6.8), while all 15 lesions (100%) with a CR and 11/14 lesions with a PR (78.5%) remain controlled at last follow up with a median duration of response of 15.5 months (8.8 – 23.3) (p<0.001). The median duration of months of ongoing response after the completion of PRIMO was 11 (0-57). The median number of treatment cycles was 14 (2-36) in all patients, and 16 (2-36) in the 26 patients that did not progress. The only variable significantly associated with PD on UVA was the lack of irAE; 10/26 (38.5%) patients who did not have an irAE experienced PD, while 0/12 patients (0%) who had an irAE experienced PD (p=0.035). Conclusions: The use of PRIMO for locally advanced cSCC produces impressive response rates that appear durable without any additional therapy. This attractive alternative to the emerging neoadjuvant paradigm deserves prospective validation with longer term follow up.

Carfilzomib plus rituximab, ifosfamide, carboplatin and etoposide (C-RICE) led to higher response, OS, and PFS in patients with transplant-eligible relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

7042 Background: The CORAL study highlighted the need to develop novel salvage regimens for R/Rr/r DLBCL previously treated with R+CHOP. Overall response rate (ORR) to second line immuno-chemotherapy was 51% with a 3-year progression free survival (PFS) of 30% following high-dose chemotherapy and autologous stem cell support (HDC-ASCS). Optimal disease control (complete remission [CR] or partial remission [PR]) prior to HDC-ADCS and more recently to chimeric antigen receptor T-cell therapy (CAR T), correlates with improved outcomes. Dysregulation of Bcl-2 family members has been associated with acquired resistance to rituximab and chemotherapy which we have previously shown may be mitigated by co-treatment with proteasome inhibition in pre-clinical model. Subsequently, we conducted a Phase I/II clinical trial evaluating the safety and efficacy of CRICE as salvage therapy for R/R DLBCL (Blood Adv. 2023 7:1146-1155). Methods: Here we retrospectively compared the clinical outcomes of R/R DLBCL patients treated with CRICE (N=28) versus RICE (N=38) on our prior clinical trial (NCT01959698). Demographic, clinical, and pathological characteristics were collected for both groups (Table). Study endpoints consisted of differences in overall response rate (ORR), CR/PR rates, median progression free survival (PFS) and overall survival (OS) between the two cohorts. Results: The addition of Carfilzomib to RICE resulted in improved clinical outcomes. A higher ORR (92.9 vs 76.3, P=0.073) and CR rates (82.1 vs. 44.7, P=0.002) were observed in CRICE vs. RICE treated patients. Multivariate analysis confirmed the higher CR rates in CRICE vs. RICE when adjusted by DLBCL subtype (GCB vs. nNon-GCB, P=0.003). More CRICE patients proceeded to HDC-ASCS (52.6% vs. 47.4%, P=0.618). The 3yr PFS rate was higher in CRICE (54%, 32-72%) vs. RICE treated patients (35%, 19-51%). While the median PFS was longer in CRICE treated patients 36.8m (0.8, 73.2) vs. 3.2m (0.5, 54.2) (RICE), it did not reach statistical significance (P=0.714). No differences in OS were observed between CRICE & RICE patients, median OS 67.3m vs. 71.8m. Conclusions: The CRICE outcomes were more striking in patients with non-GCB r/r DLBCL (ORR 85%, mPFS and OS not reached). CRICE led to high CR rates and longer PFS among r/r DLBCL patients, especially in non-GCB DLBCL patients. CRICE could be an attractive regimen to achieve disease control in r/r DLBCL patients undergoing consolidation therapy with HDC-ASCT or CAR T-cell therapy. [Table: see text]

Outcomes of Patients with Primary Mediastinal B-Cell Lymphoma Refractory or Relapsed after Frontline R-EPOCH Chemotherapy

Outcomes of Patients with Primary Mediastinal B-Cell Lymphoma Refractory or Relapsed after Frontline R-EPOCH Chemotherapy

Dynamics of Radiomic Features Following Bridging Therapy Determine CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy Outcome

Introduction: Greater burden of disease is associated with poorer outcomes after CAR T therapies. Bridging therapy (BT) is widely used to debulk or palliate between apheresis and CAR T infusion. We studied whether the degree and dynamics of radiomic cytoreduction during the bridging period are prognostic. Methods: Patients with large B-cell lymphoma (LBCL) treated with CD19 CAR T from 2016-2022 were stratified into 3 BT cohorts: 1) no BT 2) radiotherapy (RT) or 3) systemic therapy (ST) including combined ST+RT. All patients had a pre-apheresis PET. Patients in the RT or ST cohorts also had a repeat PET post-BT but pre-CAR T infusion. Radiomic parameters of interest including max SUV and metabolic tumor volume (MTV) were calculated for all scans. MTV was determined using a semi-automated method and SUV4 threshold. Max SUV and MTV pre- and post-BT were compared using Wilcoxon signed-rank tests. Kaplan Meier was used to calculate progression free survival (PFS) and overall survival (OS) from CAR T infusion; univariable and multivariable analysis were performed by Cox proportional hazards. Patients were stratified by disease burden using an absolute MTV cutpoint established based on pre-BT PET with a maximally selected log-rank statistic for PFS via the maxstat package in R. “High” and “low” MTV were defined as MTV above or below this cutpoint, respectively. To quantify the impact of effective cytoreduction during BT, we created 4 BT MTV risk groups: a) “Low” with low MTV pre and post BT, b) “High” with high MTV pre and post BT, c) “Rising” with baseline low MTV which increased to high post BT and d) “Improved” with baseline high MTV which decreased to low post BT. Results: 158 patients with LBCL (79%), high grade BCL (17%) or primary mediastinal BCL (4%) received CAR T (51% axicabtagene, 28% tisagenlecleucel, 21% lisocabtagene). 42 (27%) received no BT, 93 (59%) had ST, 23 (15%) had RT. With median follow-up of 28.6 months, 12- and 24-month PFS were 43% and 36% and OS were 68% and 54%, respectively. Median pre-BT SUV max was 19 (range: 0-47) which reduced significantly to 13 post-BT (p<0.001). Median baseline MTV was 55cc (0-2,278) which reduced 40% to 33cc post-BT (p=0.001). Of the 116 patients who received BT, 67% had any degree of quantitative cytoreduction post-BT and only 35% achieved at least 50% MTV reduction [Fig A]. In the RT bridged 2yr PFS was 52% (95% CI: 32-83) vs. No BT (37%, 95% CI: 24-56) or ST bridged (33%, 95% CI: 24-45). Our established MTV cutoff was 35.5cc and was significantly associated with PFS both pre-BT and post-BT. The MTV dynamics during BT were further prognostic [Fig B] with best PFS seen in the Low risk group (1yr PFS: 73%) and worst in the High risk (1yr PFS: 21%) and Rising risk groups. In contrast, despite high baseline MTV, the Improved risk group had comparatively better outcomes with 1yr PFS of 52%. In a multivariable model of the 116 patients who had BT, several factors were associated with poorer PFS including higher pre-BT LDH (HR 2.2, p=0.004) and BT MTV risk grouping (p<0.001). Of note, while the High risk group had significantly worse PFS vs. Low risk (HR 4.7, 95% CI: 2.1-10.5) outcomes for the Improved risk group did not differ significantly from Low risk (HR 2.1, 95% CI: 0.8-5.3). Conclusions: In our real-world experience, while most patients required BT, many did not achieve successful disease cytoreduction prior to CAR T cells. While disease extent both pre-apheresis and post-BT are prognostic, the quantitative dynamics of BT cytoreduction may further refine prognostic ability. BT responders have better outcomes while stably high or rising MTV through BT is associated with poor prognosis.

Clinical Outcomes and Patterns of Failure in Patients with High-Risk Atypical Meningioma Treated with Single Fraction vs. Hypofractionated Gamma Knife Radiosurgery

The recently completed RTOG 0539 supports fractionated radiation therapy for patients categorized as having intermediate (3 yr PFS 93.8%) or high-risk (3 yr LC 68.9%) meningiomas. Stereotactic radiosurgery (SRS) has not been widely established in the treatment of WHO grade 2 atypical meningiomas given concern that there is a greater risk of microscopic infiltration and therefore requires larger margins than safely achievable with SRS. We look to review a consecutive cohort of patients at our institution who have been diagnosed with atypical meningioma treated with either single fraction Gamma Knife SRS (GK-sfSRS) or hypofractionated Gamma Knife SRS (GK-hfSRS). We review both control rates and patterns of failure. Patients diagnosed with intermediate or high-risk WHO grade 2 meningioma per RTOG 0539 classification, without a history of prior radiation (RT) and treated with either GK-sfSRS or GK-hfSRS between 2014 to 2021 at our institution, were included. Patient charts were reviewed, and follow-up data were analyzed for local control (LC) and failure patterns. Local failure was defined as tumor recurrence within the prescription isodose line, marginal was ≤5 mm outside the prescription isodose line, and distant was >5 mm outside of the prescription isodose line Primary outcome was LC, and secondary outcomes were overall survival (OS) and progression free survival (PFS). We identified 47 pathologically confirmed WHO grade 2 meningiomas in 27 patients. 33 lesions were treated with GK-sfSRS and 14 lesions with GK-hfSRS. 6 lesions were intermediate risk, and 41 were high-risk per RTOG 0539. With a median follow up of 36 months (range 2-86 mo), the 3yr LC was 82.7%, PFS was 83.1%, and OS was 96.3%. A total of 4 patients with 8 lesions failed treatment - all with high-risk disease. All failures were local (4) or marginal (4). The 4 local failures were all from a single patient with 4 distinct meningiomas that were treated with GK-sfSRS without surgical resection. The 4 marginal failures were all in patients treated with GK-sfSRS. There were no failures in patients treated with GK-hfSRS. Our institutional data for patients with atypical meningiomas treated with radiosurgical techniques compare favorably to the patients treated with EBRT in RTOG 0539, though longer follow-up is needed to confirm these findings. Outside of one patient, no patients developed recurrence within the prescription volume. There were 4 tumors with marginal failures, suggesting that additional dural margins than what were prescribed may be meaningful. At our institution, we are increasingly moving to hypofractionated radiosurgery with 5 mm of dural margin when using radiosurgical techniques for high-risk atypical meningioma. However, longer term follow-up is needed to validate the use of radiosurgical techniques in atypical meningioma.

Impact of Consolidative Radiation on Overall and Progression Free Survival in Pediatric, Adolescent and Young Adult Metastatic Sarcoma

To determine the association between consolidative radiation and survival in pediatric, adolescent, and young adult (AYA) metastatic sarcoma MATERIALS/METHODS: Eligible patients included those diagnosed with metastatic bone or soft tissue sarcoma at ≤39 years of age. Patients whose cancer progressed prior to the time of local control were excluded. Consolidative radiation (RT) was defined as RT to all sites of metastatic disease. Kaplan Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Cox proportional hazards was used to account for confounding variables. To adjust for immortal time bias (ITB), end of local control was chosen as a landmark time. Patients (n = 77) had a median age at diagnosis of 14.5 years (range: 1.7-29.7 years). The most common histology was Ewing sarcoma (49%), followed by rhabdomyosarcoma (30%). Median follow up was 28.5 months, without significant difference between patients treated with and without consolidative RT (23.7 vs. 21.5 months, p = 0.270). Median time to completion of consolidative RT from diagnosis was 8.5 months. Ewing sarcoma was more likely to be treated with consolidative RT compared to other histologies (p<0.001). Consolidative RT was associated with improved OS (2yr OS: 81.9% vs. 57.9%, p = 0.009) and PFS (2yr PFS: 71.2% vs. 30%, p = 0.001). On multivariate analysis, after accounting for age, histology, number, and type of metastases (lung, bone or other), consolidative RT remained independently associated with improved OS (hazard ratio (HR):0.36, 95% confidence interval [CI]: 0.17, 0.78, p = 0.010) and improved PFS (HR = 0.34, 95% CI = 0.16, 0.73, p = 0.006). The OS benefit for consolidative RT persisted after adjusting for ITB (1yr OS post-local control: 80.9% vs. 89.7%, p = 0.016). The effect of consolidative RT was validated in a dataset consisting of patients who were diagnosed with localized disease but had metastatic progression (n = 30). In this metachronous population, consolidative RT remained independently associated with improved OS (HR = 0.11, 95% CI = 0.03, 0.51, p = 0.004) after accounting for age. ConsolidativeRT was independently associated with improved OS and PFS in pediatric and AYA patients with metastatic sarcoma at diagnosis. The OS benefit extended to those who underwent consolidative RT for metastatic progression. Future work should evaluate biomarkers to optimize patient selection and timing and dose of consolidative RT.

Impact of imaging frequency on progression free survival in Alliance clinical trials enrolling patients with untreated follicular lymphoma.

7520 Background: With goal of simplifying clinical trials in lymphomas, we reported that bone marrow biopsies are irrelevant for response assessment in most patients (pts) with follicular lymphoma (FL) on trials (Rutherford JCO 2023). We then investigated impact of imaging frequency in FL clinical trials. We hypothesized that progression free survival (PFS) would not be different when imaging is performed less frequently than required by trials. Methods: We identified all trials through Alliance for Clinical Trials in Oncology that enrolled untreated pts with FL from 2008-2016. We considered 2 imaging schedules: protocol specified (control) vs relaxed (X) in which response assessments at every other required time point were omitted. For each trial, we estimated PFS using Kaplan Meier methods for the 2 schedules then determined difference in PFS between schedules as % change from control schedule in 2 year (yr) PFS rate. We performed simulation studies to approximate impact of less frequent imaging on PFS estimation using 50901 (low-intermediate risk FL) and 50904 (intermediate-high risk FL, control arm). We assumed exponential distribution for PFS, where rate parameter was calculated based on observed median PFS with uniform censoring distribution. Protocols for 50901 and 50904 mandated imaging every 4 months (mos) for 2 yrs then every 6 mos (S0). We ran 1000 iterations of 100 observations using 3 tumor assessment follow up schedules: every 6 mos for 2 yrs then yearly (S1), every 8 mos for 2 yrs then yearly (S2), or yearly (S3) for simulated progression times. We calculated deviation of PFS using simulated schedules from truth (S0). Results: Across 5 FL trials, median percent change of schedule X from control schedule in estimated 2yr PFS was 2.1% (0.0-30.8%) and in estimated 4yr PFS was 0.9% (-8.6-25.7%). Disparate result in 50901 is due to small shift in events with low number of pts at risk for progression. Simulation study results by trial were: for 50901, true median PFS 1.9 yrs and average median PFS for S1, S2, and S3 of 2.05, 2.11, and 2.21 yrs; for 50904 (control arm), true median PFS 4.1 yrs and average median PFS for S1, S2, and S3 of 4.16, 4.12, and 4.05 yrs. Conclusions: Our findings support decreased frequency of imaging studies in FL clinical trials, which would improve resource use and decrease pt burden. We plan a larger analysis to confirm results. https://acknowledgments.alliancefound.org . Clinical trial information: NCT00553501 , NCT01145495 , NCT01190449 , NCT01286272 , NCT01829568 .[Table: see text]

Bone metastasis in patients with germ-cell tumors: Analysis of survival outcomes and prognostic factors.

e17029 Background: Bone metastasis (BM) is uncommon in patients with germ-cell tumor (GCT). There is lack of data regarding optimal treatment approach. We report the outcomes and prognostic factors in 99 pts with BM treated at our institution. Methods: We identified 99 pts with GCT and BM treated at Indiana University between year 1986-2021. Kaplan-Meier methods were used for progression free survival (PFS) and overall survival (OS) analysis. Results: Median age was 31.5 (range, 13.1-58.8). Primary tumor histology was non-seminoma in 77 and pure seminoma in 22. Predominant histology was seminoma in 26, yolk sac tumor 23, mixed 16, embryonal ca 12, teratoma 10, choriocarcinoma 9. Other mets sites included lungs in 68, RP LNs in 63, liver in 34, brain in 19. BM location was spine in 73, pelvic bones in 22, humerus/femur in 14, ribs in 10, sternum/clavicle in 7. Median pre-chemo AFP was 438 (range, 1-75,414) and hCG 80 (range, 0.7-1,700,000). 1L chemo was BEP x4 in 46, VIPx4 in 10, BEP x3 + EP x1 in 8, EP x4 in 8, BEP x3 in 7, VIPx3 in 1, and other in 19. Histology of BM resection for those who underwent surgery was viable non-teratoma GCT in 6, teratoma in 1, malignant transformation of teratoma in 3, and necrosis in 3. 28 had radiotherapy to symptomatic BM. 80 (82.5%) pts progressed after 1L chemo and 46 (53.5%) progressed after 2L chemo. With median f/u from diagnosis of 5.7 years, 5 yr PFS was 17.8% (95% CI 10.3-27.0) and 5 yr OS was 59.9% (95% CI 47.9-70.0). For pts with pure seminoma, 5 yr PFS was 29.8% (95% CI 12.4-49.5) and 5 yr OS 83.1% (95% CI 55.7-94.3). For non-seminoma: 5 yr PFS was 14.6% (95% CI 6.9-25.1) and 5 yr OS 52.2% (95% CI 38.4-64.2). Multivariable analysis indicated that pts with concurrent liver and/or brain mets had worse OS. Conclusions: Outcomes of pts with GCT and BM are inferior than what is expected based on IGCCCG risk categories. Pts with concurrent liver and/or brain mets have particularly worse OS outcomes. [Table: see text]

Social determinants of survival in head and neck cancer.

e18008 Background: Social demographics and health inequalities are associated with adverse outcomes in cancer. Methods: We conducted a retrospective review of 320 Head and Neck Cancer patients between 2013-2021 in a tertiary centre in Western Australia. We matched 80 Aboriginal patients with 240 non-Aboriginal patients by disease site, histology, age, and rurality. Data collected included tumour site, patient demographics, treatments, recurrences, and survival outcomes. An initial univariate analysis was performed using Chi-Square and Kaplan Meier analyses; however a multivariate analysis will be conducted for subsequent publication. Results: Median follow-up was 2.6 years (range 16 days to 9 years). 44% of patients underwent curative intent radiotherapy or chemoradiotherapy, 38% had surgery (+/- adjuvant therapies), 9% had palliative treatments, and 9% had best supportive care. Overall survival (OS) using Kaplan-Meier was inferior for Aboriginal patients compared with non-Aboriginal patients; 1 year survival (YS) 59% vs 85% and 5YS 32% vs 60% (p &lt; 0.00001). Of patients receiving curative intent treatment, relapse occurred in 47% of Aboriginal patients compared with 29% of non-Aboriginal patients (p = 0.01), with inferior progression-free survival (PFS) 1 yr PFS 71% vs 81% and 5yr PFS 52% vs 72%, p = 0.006. 2YS was highest in regional patients (77%), followed by metropolitan (68%), and lowest in remote patients (61%), p = 0.04. 21% of remote patients opted for palliative treatment despite curative treatment being recommended, compared with 3% of regional and 4% of metropolitan patients. Amongst patients receiving curative treatment (81%), metropolitan patients had the highest risk of relapse (42%), compared with remote (31%) and regional (23%), p = 0.02. Despite this, in the same group of treated patients, remote patients had the lowest survival (2YS 88% regional, 80% metropolitan, 75% remote, p = 0.04). Ever smokers had lower 1YS (91% vs 76%, p = 0.03), a higher risk of relapse (28% vs 21%, p = 0.01), and a lower likelihood of disease-free survival (53% vs 74%, p = 0.01) compared to never smokers. Alcohol excess was associated with inferior 1YS (84% 0-4 std/d, 85% 5-10 std/d, 57% &gt; 10 std/d, p = 0.00004), and a higher risk of relapse (19% for non-drinkers, 35% 1-4 std/d, 27% 5-10 std/d, and 64% for &gt; 10 std/d, p = 0.00007). Marital stability was associated with improved 1YS (88% married, 78% widowed, 78% de facto, 76% divorced, 65% single, p = 0.004). Single patients had the lowest likelihood of disease-free survival (42%), followed by divorced (50%), de facto (50%), and widowed (65%). Married patients had the best disease-free survival (66%), p = 0.002. Non-English speaking status was associated with inferior 1YS (79% vs 40%, p = 0.006). Conclusions: Aboriginal status, rurality, smoking, high alcohol consumption, single or divorced individuals, and non-English speaking were all associated with poorer outcomes.

Total Metabolic Tumor Volume Is Confirmed As Independent Prognostic Factor in Treatment Naïve Follicular Lymphoma Patients and Can be Combined with FLIPI2 to Improve Prognostic Accuracy. a FOLL12 Substudy By the Fondazione Italiana Linfomi

Aim/Introduction: The prognostic role of FDG PET/CT parameters before first line therapy in patients with Follicular Lymphoma (FL) remains unclear, with conflicting data published in the literature. To this end we evaluated the prognostic value of baseline Total Metabolic Tumor Volume (TMTV) in a large cohort of treatment-naïve FL patients enrolled in the FOLL12 trial (NCT02063685). Materials and Methods: FOLL12 is a multicenter, randomized, phase III trial that compared standard (Arm A) vs response adapted maintenance (Arm B) in patients with grade 1-3a advanced stage FL who achieved complete (CR) or partial response (PR) to induction rituximab based immunochemotherapy (R-ICT). In the current study we included patients for whom baseline FDG PET/CT was available and centrally reviewed. The TMTV was obtained by expert nuclear physicians from baseline scans by summing the metabolic volumes of all individual nodal and extra nodal lesions, using the 41% SUVmax threshold method. Univariate and multivariate analyses were performed using Cox proportional hazard model. Main study endpoint was Progression Free Survival (PFS). Results: starting from the FOLL12 trial population, 692/807 patients were included in this study; 48% were older than 60 years, 89% had stage III-IV disease and 40% had a high-risk FLIPI-2 score(3-5 risk factors). Overall, the 5-year PFS was 79% (95% CI, 76 to 82%) and the median TMTV was 242 mL (IQR=446). The optimal cutoff identified for TMTV was 200ml. TMTV values were higher in association with unfavorable prognostic features (Hb <12 g/dl, LoDLIN > 6cm, elevated beta2 microglobulin and LDH, and number of nodal areas >4) whereas were similar between study arms, and ICT regimens. In univariate analysis, 5-year PFS was significantly lower for patients with high vs low TMTV (60% vs 75%; HR=1.87 [95%CI: 1.41-2.49], p<0.001). The correlation between TMTV and PFS was confirmed both in the standard maintenance arm and in the response adapted arm of the FOLL12 trial and the independent prognostic role of TMTV was confirmed when adjusted by study arm, FLIPI-2, and type of ICT. In multivariate analysis, high TMTV (HR 1.47 (1.09 - 2.00); p=0.012) and high risk FLIPI2 (3-5 RFs: HR2.05 (1.54 - 2.73) p<0.001) retained their independent prognostic role for predicting PFS. Three groups of patients were identified which were associated with different 5-year PFS rates; TMTV < 200ml and intermediate FLIPI2: N=241 (35%), 5yr PFS 78% (95% CI 71-83); TMTV > 200ml or high risk FLIPI2: N=237 (34%), 5yr PFS 68% (60-74), HR 1.53 (1.06 - 2.22); TMTV >200ml and high risk FLIPI2: N=214 (31%) 5-yr PFS 51% (43-58), HR 2.96 (2.10-4.19). The combined TMTV + FLIPI2 model was internally validated with 1000 bootstrap resampling (c-Harrel 0.616) Conclusion: Pre-treatment TMTV is confirmed as a strong independent predictor of PFS in patients with FL receiving frontline R-based ICT The combination of TMTV and FLIPI2 may contribute to improve risk stratification in guiding risk adapted therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of Extranodal Disease Involvement on Outcomes in Post-Transplant Lymphoproliferative Disorder

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ or hematopoietic transplantation and is composed of a heterogeneous group of lymphoid disorders ranging from plasmacytic hyperplasia to aggressive lymphomas. Several factors such as age, performance status, lactate dehydrogenase, presence of B-symptoms, and disease stage have been identified as poor prognostic factors in PTLD. Extranodal disease (END) is present in the majority (50-80%) of patient (pts) at the time of diagnosis and has been shown to a be predictor of overall survival in this patient population; in particular, the presence of disease involvement in the central nervous system (CNS) or bone marrow (BM) has been shown to be poor prognostic factor. In this single center, retrospective analysis we examine the impact of END on outcomes in pts with PTLD. Methods: Pts with a diagnosis of PTLD were identified by Electronic Medical Records database query. Inclusion criteria were age ≥ 18 years at the time of diagnosis, confirmation of PTLD by internal pathology review, primary diagnosis from 2008-2018, and receipt of therapy and surveillance care at Northwestern University in Chicago, Illinois, USA. Exploratory univariate analyses were performed using Kaplan-Meier estimates with 95% confidence intervals and log-rank p-values for time-to-event outcomes; significance was set at p < 0.05. Response to treatment and disease progression were classified per provider-specific interpretations of clinical data as assessed by patient chart review. Results: A total of 182 pts with a diagnosis of PTLD were identified by database query and 111 pts met inclusion criteria. Of the 111 pts included in this analysis, 82 pts (73.9%) were male with a median age at diagnosis of 56 years (range 19-85) (table 1). The median time from transplant to diagnosis was 79 months (range 2-324). For all pts, the five-year overall-survival (OS) and progression-free survival (PFS) were 70.7% and 49.7%, respectively. Eighty-two pts (73.9%) had END at the time of diagnosis. There was no difference in 5yr OS between pts with END and those without END (69.5% vs 73.3%, p=0.56). A trend towards improved PFS was noted in patients without END compared to those patients with END; however, this difference was not statistically significant (70.6% vs 42.4%, p=0.09). Out of the 82 pts with END, 12 pts (14.6%) had multiple-site disease involvement, 41 pts (50%) had only gastrointestinal (GI) involvement, 13 pts (15.9%) CNS, 5 pts (6.1%), 4 pts (4.9%) pulmonary involvement, and 7 pts (8.5%) had other organ site involvement (renal, musculoskeletal, or oropharyngeal). There was no difference in 5yr OS and PFS between patients with single organ involvement of END vs multiple-site END at time of diagnosis. There was no difference in OS in patient with PTLD when stratified out by specific site involvement; however, patients with END disease involvement of GI tract had significantly inferior PFS than those patients without GI (27.3% vs 60.6%, p=0.05) (Figure 1). There was no difference in PFS across the other sites of END involvement. Conclusions: This study represents one of the largest retrospective cohorts of PTLD reported in the literature. We show that overall, the presence of END does not correlate to worse PFS or OS in patients with PTLD. The presence of GI involvement at the time of diagnosis may correlate to worse PFS. No additional specific site of organ involvement, including presence of BM or CNS disease, correlated to worse overall prognosis in this patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Effect of Tumor Margin Status on Progression-Free Survival (PFS) in Patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC) after Transoral Robotic Surgery (TORS)

<h3>Purpose/Objective(s)</h3> Human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPSCC) has an excellent prognosis, and many patients are treated with transoral robotic surgery (TORS). It is unclear if adjuvant therapy post-TORS in the HPV-positive population should be guided by the same criteria as HPV-negative OPSCC. We sought to examine post-TORS outcomes from a single institution. <h3>Materials/Methods</h3> From a prospectively collected single institution database of head/neck cancer patients, we retrospectively identified patients with OPSCC who underwent TORS from 2015-2021. Demographic, clinical, and pathologic information including margin status and distance from tumor were assessed. Patients were stratified by tumor margin status (positive and negative tumor margin status). Progression-free survival (PFS) probabilities were estimated using the Kaplan-Meier method. Distributions were compared between groups using the log-rank test statistic. <h3>Results</h3> 163 patients who underwent TORS were selected (152 with HPV-positive tumors) with a median age of 59 years (range, 31-79). Most patients had tonsil primaries (115, 70.6%) and T1-2 disease (T1 72 (44.2%), T2 77 (47.2%)). 131 had negative surgical margins (-SM), 32 had positive surgical margins (+SM). There was no significant difference between the two groups. Median distance from negative tumor margin was 0.5mm (range, 0.5-5). PFS analyses were adjusted for HPV-status and pathological features including PNI and LVI. 2yr PFS for -SM was 98.4% vs 93.8% for +SM (p < 0.005). Outcomes for patients with -SM by adjuvant therapy were (n, 2yr PFS): observation (23, 95.2%), radiation (65, 95.3%), chemoradiation (43, 92.9%, p < 0.005). Outcomes for patients with +SM by adjuvant therapy were (n, 2yr PFS): observation (3 patients declined adjuvant therapy, 66.7%), radiation (8 patients declined concurrent chemotherapy, 94.6%), chemoradiation (21, 91.3%, p < 0.005, limited by majority of patients receiving adjuvant chemoradiation). When examining by tumor margin distance and impact on PFS, each additional millimeter resected from tumor defining -SM increased 2yr PFS by 24.3% starting from 0.5mm until 2.4mm. <h3>Conclusion</h3> +SM post-TORS in a largely HPV-positive population from a single institution portends worse 2yr PFS, with a decrement of approximately 5%. In -SM patients, distance from tumor to margin impacted PFS up to 2.4mm, confirming ECOG 3311 cutoff of 3mm as defining close margins. Thus, +SM and close margins continue to impact outcomes in this good risk-population with early-stage HPV-positive cancer and should inform adjuvant therapy recommendations. Ongoing prospective studies investigating de-escalation of adjuvant therapy post-TORS represent cautious efforts to identify means to reduce toxicity in this population.

Outcomes and Patterns of Failure in Early-Stage, High-Risk Histology Endometrial Cancer Treated with Vaginal Cuff Brachytherapy

<h3>Purpose/Objective(s)</h3> The majority of patient diagnosed with endometrial cancer have low-risk endometrioid histology with an excellent prognosis. There is a small subset of patients however, who are diagnosed with a histology for which the outcomes are not as good. Serous, clear cell, carcinosarcoma and neuroendocrine carcinomas are more aggressive histological variants with a propensity for early extrauterine spread resulting in higher rates of death. They typically receive upfront chemotherapy but questions remain as to whether the increased risk of spread warrants adjuvant pelvic radiation or whether the risk can be mitigated with vaginal cuff brachytherapy (VCB). We aim to describe the outcomes and patterns of failure in early-stage, high-risk histology patients in which pelvic radiation was omitted, in order to shed light on the risk of pelvic failure. <h3>Materials/Methods</h3> A retrospective chart review was performed on patients treated for high-risk histology, early-stage uterine cancer at our institution. Patients receiving adjuvant VCB +/- chemotherapy were included. Demographic and clinical data was collected. Descriptive statistics were used to summarize variables. Kaplan-Meier analysis was used to estimate the survival probabilities. For all time to event outcomes, univariate cox proportional hazard regression models were built for clinically correlated variables. A two-tailed p<0.05 was considered statistically significant. <h3>Results</h3> 77 patients with early-stage carcinosarcoma (23.4%), clear cell (35.1%), serous (40.3%) and neuroendocrine carcinoma (1.3%) of the uterus were reviewed. Median follow up was 43 months (range 7-117 months). 2yr and 5yr overall survival (OS), metastasis free survival (MFS) and progression free survival (PFS) were 95% and 92%, 95% and 90% and 91% and 82% respectively. Of the 9 patients (11.7%) that recurred, 2 patients (2.6%) had isolated vaginal cuff recurrences, 4 patients (5.2%) had isolated pelvic recurrences and 3 patients (3.9%) had both a local and distant failure. Of the 27 individual sites of recurrence, 21 (77.8%) were below the level of L4. <h3>Conclusion</h3> In patients with early stage, high risk histology endometrial cancer treated with adjuvant VCB +/- chemotherapy, the 2yr and 5yr PFS was 91% and 82% respectively. All patients that recurred had some component of pelvic failure.

Outcomes by BCL2 and MYC expression and rearrangements in untreated diffuse large B-cell lymphoma (DLBCL) from the POLARIX trial.

7517 Background: Overexpression of BCL2 and MYC, and translocation of MYC, BCL2, and BCL6, are associated with poorer outcomes in patients (pts) with DLBCL (Horn et al. Blood 2013). We previously reported progression-free survival (PFS) from POLARIX in subgroups of pts with DLBCL receiving Pola-R-CHP or R-CHOP, including pts with double expressor lymphoma (DEL; favoring Pola-R-CHP: hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.42–0.97), and double- or triple-hit lymphoma (DHL/THL; favoring R-CHOP: HR 3.81, 95% CI 0.82–17.64) (Tilly et al. NEJM 2022). In this prespecified exploratory analysis, we further analyzed immunohistochemistry (IHC) expression status of BCL2, MYC, and rearrangements (R) of BCL2, BCL6 and MYC as independent prognostic markers. We also explored the prognostic impact of DEL within treatment arms. Methods: BCL2 and MYC protein expression were assessed by IHC and identified as IHC+ (≥50% [BCL2]/≥40% [MYC]) or IHC−; MYC-R, BCL2-R, and BCL6-R were detected by fluorescence in situ hybridization (Tilly et al. NEJM, 2022). Exploratory multivariate Cox regression models were adjusted for treatment, stratification factors (IPI, bulky disease, geographic region), age &gt;60 years, cell of origin, and biomarker evaluated, as appropriate. Results: The prevalence, univariate HR, and 2-year (yr) PFS estimates of BCL2+/MYC+ and BCL2-R/ MYC-R/ BCL6-R subgroups are presented (Table) except for BCL6-R, because all 4 PFS events in this subgroup were with Pola-R-CHP. Multivariate analyses results for Pola-R-CHP vs R-CHOP in pts with BCL2+ (HR 0.60, 95% CI 0.43–0.86) and in pts with MYC+ (HR 0.63, 95% CI 0.45–0.89) were similar to results of univariate analyses. Multivariate analyses of other subgroups were not performed due to the low pt number with BCL2-R/ MYC-R/ BCL6-R. While pts with DEL treated with Pola-R-CHP had improved PFS vs pts treated with R-CHOP (HR 0.64, 0.42–0.97), the prognostic impact of DEL vs non-DEL was more pronounced with R-CHOP (univariate HR 1.53, 95% CI 1.06–2.21; multivariate HR 1.29, 95% CI 0.88–1.91) vs Pola-R-CHP (univariate HR 1.10, 95% CI 0.72–1.69; multivariate HR 1.42, 95% CI 0.89–2.28). Conclusions: Multivariate analyses support the benefit of Pola-R-CHP in pts with BCL2+ and MYC+ DLBCL. The poor prognostic impact associated with DEL appears reduced in Pola-R-CHP- vs R-CHOP-treated pts. Clinical trial information: NCT03274492. [Table: see text]

Outcomes according to histological variants of urothelial carcinoma after neoadjuvant chemotherapy in the GETUG-AFU V05 VESPER trial.

533 Background: The histological variants of urothelial carcinoma (UC) may impact the outcomes after neoadjuvant chemotherapy in muscle invasive bladder cancer (MIBC). Previous studies provided contradictory results because of bias related to their retrospective design. Our aim was to assess pathological response and 3-year (yr) progression free survival (PFS) according to UC variants for patients included within the French prospective Vesper clinical trial (NCT01812369). Methods: 493 patients received dose-dense Methotrexate, Vinblastine, Doxorubicin and Cisplatin (dd-MVAC) or Gemcitabine and Cisplatin (GC) after randomization in the VESPER trial. This ancillary study was restricted to 437 patients treated in neoadjuvant setting. A central pathological review of initial transurethral diagnostic specimens allowed to assess UC variants (if ≥10% tumor area) and the presence of tumor emboli, perineural invasion, and CIS. Results: Slides were available for central review in 303 cases. UC variants were present in 180 patients (59%). Tumor emboli, perineural invasion, and CIS were noticed in 119 (39%), 24 (8%) and 143 (47%) cases. In comparison with pure UC, the presence of UC variants was not associated with different complete pathological response (ypT0N0) (OR 0.78, 95% CI 0.48-1.27) or 3 yr PFS (HR 1.25, 95%CI 0.83-1.86). Tumor emboli were negatively associated with ypT0N0 (OR 0.57, 95%CI 0.35-0.95, p = 0.029), organ confined disease (OR 0.44, 95%CI 0.26-0.75, p = 0.002) and 3 yr PFS (HR 1.81, 95%CI 1.23-2.67, p = 0.003). Perineural invasion were negatively associated with organ confined disease (OR 0.29, 95%CI 0.12-0.68, p = 0.005) and 3 yr PFS (HR 2.54, 95%CI 1.47-4.40, p &lt; 0.001). There was no association for CIS. Conclusions: In the VESPER trial, UC variants were not associated with distinct pathological response or 3 yr PFS after neoadjuvant chemotherapy. Future studies will determine whether molecular subtypes are associated or not with distinct outcome.

A Phase 1-2 Trial of Concurrent Radiation Therapy, Cisplatin and BMX-001 in Locally Advanced Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Prevention/mitigation of oral mucositis (OM) and xerostomia are challenges to the use of chemoradiation (CRT) for advanced head and neck squamous ca (HNSCC). MnTnBuOE-2-PyP5⁺(BMX-001) is a lipophilic manganese metalloporphyrin superoxide dismutase mimic that protects against radiation and chemotherapy induced OM in orthotopic animal tumor models. This study objective was to determine the toxicity profile of BMX-001 given during CRT for locally advanced HNSCC and to measure the incidence of severe (CTCAE v 4.03 grade 3-4) OM and xerostomia. <h3>Materials/Methods</h3> Multi-center prospective phase 1-2 open label trial for patients with AJCC 7 stage III/IVB HNSCC undergoing concurrent RT/cisplatin, curative (70 Gy) or post-op (60-66 Gy). BMX-001 was administered subcutaneously 2x/week during CRT with an initial loading dose given up to 4 days prior to the start of CRT. Two additional doses of BMX-001 were given in the first week post-CRT. A 3+3 design was used. BMX-001 dose levels were 1: 7 mg load/3.5 mg maintenance; 2: 14 mg load/ 7mg maintenance; 3: 28 mg load/ 14 mg maintenance. Level 3 was expanded to assess phase 2 endpoints. Co-primary endpoints: toxicity of BMX-001 and the incidence of severe (grade 3-4) OM. OM was evaluated 2x/week during CRT and then weekly for 4 additional weeks. Secondary endpoints: median duration and time to onset of grade 3-4 OM, grade ≥2 xerostomia 1- and 6-months post-CRT, and progression-free survival (PFS). <h3>Results</h3> A total of 29 patients (M:F = 25:4) were enrolled from 5/2017-12/2019. Primary sites: p16+ oropharynx 25 (86%), nasopharynx (1), hard palate (1), unknown primary (2). Median age: 62 yo (IQR:56-67). Dose levels were 1 (3); 2 (3); dose 3 (23). Median RT dose: 70 Gy (IQR 70-70). 79.3% of subjects received > 200mg/m² of CDDP. All subjects on levels 1 and 2 received all BMX-001 as prescribed by protocol. Level 3, 19/23 (83%) received all doses of BMX-001. All patients had a grade 1 injection site reaction. There were 2 (7%) mild AEs related to QT interval prolongation and 3 serious adverse events (SAE) categorized as possibly related to BMX-001: hypotension, fever with pancytopenia, and hyponatremia. Other SAEs (n = 19) were judged to be expected due to the nature of the disease or treatment with CRT. Incidence of severe OM was 41% (median duration 25 days, IQR 25-47). Median time to onset of severe OM was 43 (IQR 34-52) days; 83.3% cases of severe OM resolved by 5 weeks post-CRT. Incidence of grade ≥ 2 xerostomia was 18%, 8%, and 9% at 1, 6, and 12 months respectively post-CRT. Mean unstimulated whole saliva production was 0.69 ml/min at baseline and 0.29 ml/min at 1 yr. Mean stimulated whole saliva production was 1.38 ml/min at baseline and 0.72ml/min at 1 yr. Median follow up was 20 mo. 1 yr PFS was 96.6%. <h3>Conclusion</h3> CRT and 2x/week BMX-001 was safe in HNSCC at the highest dose tested. Promising rates of severe OM and xerostomia justify further investigation in HNSCC patients receiving CRT.

Prognostic Factors and the Impact of Frontline Therapy in Peripheral T-Cell Lymphoma: A Multicenter Australian Study

BackgroundPeripheral T cell lymphomas (PTCL) are a heterogeneous group of lymphomas that have poor outcomes with current frontline chemotherapeutic strategies. Cyclophosphamide, vincristine, doxorubicin and prednisone, with or without the inclusion of etoposide (CHO(E)P), remains the standard of care, although scarce data exist regarding the benefit of intensive regimens, including hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high dose methotrexate/cytarabine (HyperCVAD). This multicenter study aims to characterize presenting features, prognostic factors and the influence of frontline therapy in patients (pts) with PTCL.MethodsWe retrospectively analysed presenting features, frontline therapy and outcomes of all pts diagnosed with PTCL at the 3 tertiary referral centers within Western Australia from 2005-2014. Overall survival (OS) and progression free survival (PFS) were calculated by the Kaplan Meier method. Univariate comparisons were made by log rank test and multivariate analysis (MVA) performed using step-wise Cox regression. Comparisons between categorical variables were made using Fisher's exact tests.ResultsA total of 98 pts were included in the analysis, with a median follow-up of 4.6 years (range 0.1 - 8.6). Median age was 64 years and 78% presented with advanced stage (III-IV) disease. Complete pt characteristics and histological subtypes are presented in Table 1.Most pts were treated with CHO(E)P (47%) or HyperCVAD (21%), with a smaller proportion receiving reduced intensity chemotherapy (9%), other therapy (12%) or supportive care alone (10%).Four year PFS was 21% (95% CI 12.2 - 29.8%) and 4 year OS was 34% (24.2 - 43.8%). Excluding pts treated with palliative intent, the overall response rate (ORR) was 73%, with a complete response rate (CRR) of 59%.OS was strongly predicted by International Prognostic Index score (IPI) (Figure 1). In MVA, age, elevated LDH and >1 extranodal sites were found to be significantly associated with survival, whereas marrow involvement, B symptoms and stage were not (Table 2).We then restricted the analysis to pts treated initially with either CHO(E)P or HyperCVAD to compare outcomes between these two commonly used regimens at our centers. Response rates were similar with an ORR/CRR to CHO(E)P of 78%/67%, and 76%/61% to HyperCVAD (p=0.90). Likewise, 4yr PFS did not differ significantly between the two regimens - CHO(E)P: 20% (6.9 - 33.1%) vs. HyperCVAD: 33% (12.6 - 53.4%), p = 0.30. On univariate analysis (UVA), 4yr OS was 27% (13.3 - 40.7%) for CHO(E)P and 62% (40.4 - 83.6%) for HyperCVAD, p = 0.042. On MVA adjusted for age, LDH and extranodal sites, there was no significant difference between treatment groups (Table 3).Consolidation stem cell transplantation (SCT) following response to first line chemotherapy was performed in only 6 (10%) pts and occurred more frequently in pts initially treated with HyperCVAD (4/16 [25%] vs. 2/36 [6%], p=0.074). In relapsed or refractory disease, pts treated initially with HyperCVAD were more likely than those treated with CHOP to receive salvage chemotherapy (11/12 [92%] vs. 20/33 [61%], p=0.046) and have SCT incorporated into subsequent lines of therapy (7/12 [58%] vs. 4/33 [12%], p=0.003).Pts treated with reduced intensity chemotherapy had poor outcomes, with median OS of 3 months. Those receiving only supportive care had a median OS of 0.8 months.ConclusionWhilst pts with PTCL presenting with low risk (IPI 0-1) disease have favourable outcomes, the majority present with higher risk disease and have poor long-term survival with current frontline therapy. Survival in our cohort was strongly associated with IPI risk factors including age, elevated LDH and multiple extranodal sites.The use of HyperCVAD did not improve response rate or PFS when compared to CHO(E)P in our pts. The superior OS noted on UVA for this group was lost on MVA, and appears to be explained by selection of younger, fitter pts, more of whom underwent salvage therapy, including autologous or allogeneic SCT, at time of progression. Whilst some expert guidelines support SCT as part of initial therapy (Moskowitz, Blood 2014), this was seldom performed at our centers.Our results do not support the frontline use of HyperCVAD over CHO(E)P in PTCL. Given poor outcomes with current chemotherapeutic options, alternative induction regimens incorporating novel agents are urgently required. [Display omitted] DisclosuresCull:Amgen Australia: Other: travel expenses Lugano lymphoma conference 2017; Takeda Australia: Other: travel expenses Highlights of ASH march 2017, Brisbane.

Phase II trial of atezolizumab (A) + carboplatin (C) + pemetrexed (P) + bevacizumab (B) in pts with stage IV non-squamous non-small cell lung cancer (NSq-NSCLC): Big Ten Cancer Research Consortium Study LUN 17-139.

9034 Background: The addition of A to C+ Paclitaxel (Pac) + plus B improved progression free survival (PFS) and overall survival (OS) compared with C + Pac + B alone in pts with metastatic NS-NSCLC. However, C + Pem is more commonly used for this patient population with a shorter infusion time and favorable toxicity profile compared with Pac. Methods: Multicenter single arm phase II clinical trial of chemo and immunotherapy-naïve pts with stage IV NSq-NSCLC. All pts received A (1200 mg, D1) + C (AUC 5, D1) + P (500 mg/m2, D1) + B (15mg/kg D1) q3 week x4. If non-PD, pts could receive maintenance APB until PD or intolerable side effects. The primary endpoint was 1 yr. PFS. Sample size of 42 planned with 87% power and two-sided type I error of 0.05 for 1 yr PFS. Secondary endpoints included ORR, disease control rate (DCR) [defined by CR + PR + SD], and toxicity. Results: 30 pts were enrolled from 11/15/2018 to 10/5/2020. The study was closed early due to 3 patient deaths, possibly related to treatment (VTE, Febrile neutropenia, colonic perforation). Median age 64 (range 38-83); M/F 20/10; mutations in EGFR/ALK/KRAS/BRAF (5/1/4/2); PD-L1 TPS &lt; 1%/1-49%/ &gt; 50% (9/14/6) and one pt did not have PDL-1 status. Median f/u was11.6 mos (range 1-20). ORR 35.71% (95% CI: 18.64%-55.95%), DCR 92.85% (95% CI: 83%-100%). 1yr PFS and OS were 55.27% and 82.90% respectively. The most common G III and G II toxicity were HTN (20%) and fatigue (33.3%).3 pts had G IV toxicity (Anemia, Febrile neutropenia and colonic perforation) and 2 pts had Grade (G) V toxicity (VTE, Hypoxia/Sepsis). Conclusions: Atezolizumab + Carboplatin + Pemetrexed + Bevacizumab was associated with longer DCR, PFS, and OS than historical controls. 3 on-treatment deaths, possibly related to therapy (more likely bevacizumab), prompted early closure. A phase 3 study evaluating this regimen is ongoing by another group NCT03786692. Clinical trial information: NCT03713944.

Salvage therapies in transplant-eligible relapsed classic Hodgkin lymphoma, are novel regimens better?

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass &gt; 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p&lt;0.01). 110 (53%) went to ASCT in CR, 74 (36%) in partial response (PR) and 11% in progressive disease (PD). 43 received BV maintenance (BVm) after ASCT. Pts going to ASCT in PR or PD had significantly lower progression free survival (PFS) compared to pts in CR (2 yr PFS: 62%, 18% vs 77%, respectively, p&lt;0.0001) in univariate and multivariate models. There was no difference in PFS and overall survival (OS) by type of ST. BVm was associated with higher PFS (HR 0.3 (CI95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p&lt;0.001). For pts transplanted in CR, there was no significant difference in PFS and OS by type of ST but higher number of ST predicted lower OS (HR 2.4 (CI95 1.2-3.5), p&lt;0.01). Conclusions: Type of ST did not predict survival, response to and number of ST did. For pts with CR, number of ST not type of ST predicted survival. BBV had higher response rates, higher rates of bridge to ASCT, and may be a preferable ST than ICE. Large, randomized trials are needed to evaluate efficacy of BBV compared to ICE.[Table: see text]

Paclitaxel, ifosfamide &amp; cisplatin (TIP) as second-line therapy for germ cell tumors (GCT):Long-term follow-up and expansion cohort.

386 Background: TIP was established as an effective second-line regimen in a phase II study of 46 patients (pts) with relapsed GCT and favorable risk factors (Kondagunta, JCO 2005). Here, we report long-term follow up from this trial and outcomes for additional pts who subsequently received TIP off protocol. Methods: Eligiblepts included those who received TIP on the original phase II trial (original cohort) or who received TIP following study closure but would have met the trial inclusion criteria (expansion cohort). An additional exploratory cohort was comprised of pts with unfavorable risk factors who would not have met the original trial criteria. The primary endpoint was favorable response rate (FRR), which included complete responses (CR) and partial responses with negative markers (PR-). Overall survival (OS), progression free survival (PFS), and relapse rates were also evaluated. Results: Of 204 pts who received TIP for GCT at our institution from 5/1994 to 7/2019, 87 (original cohort, n=46; expansion cohort, n=41) met the inclusion criteria and were evaluable for the main analysis. An additional 17 pts were analyzed in the exploratory cohort (unfavorable risk factor: PR- lasting &lt;6months or IR, n=13; prior adjuvant therapy, n=4). 100 pts were excluded due to participation in an ongoing clinical trial (n=17), receipt of TIP as their first regimen (n=74) or in the adjuvant (n=3) setting, or insufficient data (n=6). Baseline characteristics and efficacy data are displayed in the table below. In the main cohort, 70/87 (80%) pts achieved a favorable response. With median follow-up of 10.2 years (yrs) [original, 14.3 yrs; expansion 6.5 yrs] 26 deaths were observed. 5yr and 10yr OS rates were 72% (95% CI 63, 83) and 69% (95% CI 59, 80) respectively. 5yr and 10yr PFS were 70% (95% CI 61, 81) and 67% (95% CI 57, 78). In the exploratory cohort, there were 7 deaths at median follow-up of 6.2 yrs with 5yr OS of 56% (95% CI 35, 87) and 5yr PFS of 59% (95% CI 40, 88). Conclusions: Long-term follow-up and additional experience supports the use of TIP as second-line therapy for GCT. Similar outcomes were seen for our exploratory and main cohorts, suggesting benefit with TIP outside of those with a favorable prognosis. [Table: see text]