Comparison of Demographics, Treatment Patterns and Outcomes Among Primary Central Nervous System Lymphoma (PCNSL) Patients Treated at a Safety-Net Hospital Versus a Tertiary Academic Institution within the Same Healthcare System

Introduction: Primary CNS lymphomas (PCNSL) are rare, aggressive, extra-nodal, non-Hodgkin lymphomas confined to the CNS. Other than high-dose methotrexate (MTX) based induction regimens, there are no established standards-of-care for managing PCNSL. Treatment practices across institutions vary regionally and globally. At safety-net hospitals, there are often access issues, delays in seeking medical care, and limited treatment options due to insurance barriers and other prohibitive costs. This study compares the demographics, treatment patterns, and survival outcomes among PCNSL patients treated at a safety-net hospital versus a tertiary academic institution within the same healthcare system. Methods: Medical records of 94 patients who were treated for PCNSL from 2007-2020, at either a public safety-net hospital (n=34) or an academic tertiary-care center (n=60), both serving the same metroplex, were analyzed. Demographics, Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic class, International Extranodal Study Group (IELSG) score, induction and consolidation treatment modalities used, and survival outcomes were compared between the 2 groups. Categorical variables and response rates were compared using Fisher's exact test. Continuous variables were compared using Mann-Whitney U test. Survival functions for overall- and progression-free survival (OS and PFS) were estimated by the Kaplan-Meier method and compared using a log-rank test. Cox proportional hazards regression was used for multivariate analysis. Results: Baseline characteristics of the study population is shown in Table 1. Compared to the tertiary academic center, patients at the safety-net hospital were significantly younger, had better Karnofsky performance status (KPS) and MSKCC prognostic class, and were more commonly Black or Hispanic, male, and HIV positive. Median follow-up was 39.4 months for surviving patients and 13.1 months for all patients. Induction regimens used were either chemotherapy (n = 74) or palliative whole brain radiation therapy (WBRT) (n = 16). Chemotherapy regimens were predominantly MTX-based (71/74, 95.9%). Safety-net patients were significantly less likely to receive induction chemotherapy (67.6% vs 85%, p = 0.004). Overall response to chemo-based induction was 70.3%. There was no significant difference in response rate to chemo-based induction between safety-net and academic center patients (73.9% vs 68.6%, p = 0.786). Patients who had a good response to induction chemotherapy (n = 52) were either given consolidative WBRT (n =11), autologous stem cell transplant (ASCT) (n = 14), chemotherapy (n = 17), or no further treatment (n = 10). When comparing safety-net and academic center patients, hospital location did not significantly affect whether patients received consolidation therapy (82.4% vs. 80%, p = 0.735). Safety-net hospital patients were significantly less likely to receive ASCT (0% vs. 40%, p = 0.001) and had higher rates of consolidative WBRT (41.2% vs 11.4%, p = 0.03). OS (71.7% vs. 51.1%, p = 0.218) and PFS (54.9% vs. 57.4%, p = 0.967) were not significantly different between safety-net and tertiary academic hospitals when adjusted for age and KPS. In a subset analysis, excluding patients who only received palliative care, there also were no differences in OS (68.9% vs 55.2%, p = 0.309) and PFS (50.3% vs 57.4%, p = 0.719) between hospitals (Figure 1). Patients who received consolidation treatment had significantly higher OS (84.8% vs 34.0%) and PFS (77.0% vs 30.3%), after adjusting for age and KPS (p = 0.001 for both). There were no significant differences between type of consolidation strategy employed for OS (p = 0.801) or PFS (p = 0.899). Conclusions: Safety-net patients with PCNSL were less likely to receive induction chemotherapy and could not receive ASCT as consolidation due to insurance barriers. Despite these differences in patterns of treatment, they had similar outcomes in terms of OS and PFS, even after adjusting for age and performance status. Consolidation treatments improved outcomes and it is critical to ensure eligible patients receive them, though the optimal type of consolidation remains unknown. This study is limited by the small sample size and retrospective analysis. Research to unearth the biologic heterogeneity of PCNSL and develop predictive biomarkers will be critical to personalize and optimize management strategies for these patients. Disclosures Awan: Genentech: Consultancy; MEI Pharma: Consultancy; Janssen: Consultancy; Astrazeneca: Consultancy; Celgene: Consultancy; Blueprint medicines: Consultancy; Sunesis: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Consultancy; Gilead Sciences: Consultancy; Kite Pharma: Consultancy; Dava Oncology: Consultancy; Abbvie: Consultancy. Desai:Boston Scientific: Consultancy, Other: Trial Finding.

IMRT with concomitant boost versus conventional radiation in the setting of sequential chemoradiotherapy for oropharyngeal cancer

ObjectivesThe aim of this study was to assess the efficacy of IMRT with concomitant boost simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) compared with conventional radiation in the setting of sequential chemoradiotherapy (induction chemoradiotherapy(ICRT)) for patients with advanced oropharynx cancer (OPC).Materials and methodsA single-institutional retrospective review was conducted on 84 patients (conventional radiation,n= 36; SIB-IMRT,n= 48) with stage III and IV OPC, who underwent definitive ICRT from 2002 to 2012. The study endpoints included overall survival (OS) and locoregional control (LRC).ResultsThe median follow-up of the matched cohorts resulted similar (30 months for 3D-radiation technique versus 37 months for IMRT), and baseline characteristics were generally balanced between the two groups. However, patients managed with conventional radiation were less likely to have positron emission tomography-computed tomography (PET-CT) for staging and to receive induction chemotherapy with TPF. A multivariate Cox proportional hazard model showed that OS and LRC were associated with several known prognostic factors, along with radiation modality (SIB-IMRT versus conventional radiation, hazard ratio 0·27,p= 0·004; hazard ratio 0·31,p= 0·006; for OS and LRC, respectively).ConclusionsThe adoption of SIB-IMRTversusconventional radiation may produce a clinical benefit in OS and LRC among patients receiving ICRT for advanced OPC.

Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients With Acute Myeloid Leukemia

Purpose There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved survival for the majority of patients when adding gemtuzumab ozogamicin (GO) to induction chemotherapy. Patients and Methods Untreated patients with AML or high-risk myelodysplastic syndrome (median age, 67 years; range, 51 to 84 years) were randomly assigned to receive induction chemotherapy with either daunorubicin/ara-C or daunorubicin/clofarabine, with (n = 559) or without (n = 556) GO 3 mg/m2 on day 1 of course one of therapy. The primary end point was overall survival (OS). Results The overall response rate was 69% (complete remission [CR], 60%; CR with incomplete recovery [CRi], 9%), with no difference between GO (70%) and no GO (68%) arms. There was no difference in 30- or 60-day mortality and no major increase in toxicity with GO. With median follow-up of 30 months (range, 5.5 to 54.6 months), 3-year cumulative incidence of relapse was significantly lower with GO (68% v 76%; hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .007), and 3-year survival was significantly better (25% v 20%; HR, 0.87; 95% CI, 0.76 to 1.00; P = .05). The benefit was apparent across subgroups. There was no interaction with other treatment interventions. A meta-analysis of 2,228 patients in two United Kingdom National Cancer Research Institute trials showed significant improvements in relapse (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002) and OS (HR, 0.88; 95% CI, 0.79 to 0.98; P = .02). Conclusion Adding GO (3 mg/m2) to induction chemotherapy reduces relapse risk and improves survival with little increase in toxicity.

Reduced-Intensity Cord Blood Transplantation without Preceding Remission Induction Therapy Induces Durable Remission in Patients with Relapsed Acute Leukemia After the First Allogeneic Stem Cell Transplantation.

Abstract 4341 Relapses in acute leukemia (AL) following allogeneic stem cell transplantation (allo-SCT), particularly those relapses within 1 year after transplantation, are often refractory to induction chemotherapy. Patients with this type of relapse rarely achieve long-term remission even after the second SCT. Cord blood transplantation, performed in a timely manner, may improve treatment outcomes in these patients. To assess the effectiveness of second cord blood transplantation (CBT) with a reduced intensity conditioning (RIC) regimen early after the diagnosis of leukemia relapse, we retrospectively analyzed outcomes from RIC-CBT without preceding remission induction therapy in 11 consecutive patients. Between 2007 and 2009, we performed CBTs with a RIC regimen for 11 patients with AL who relapsed after allo-SCT. Seven patients were diagnosed with acute myeloid leukemia and four with acute lymphoblastic leukemia. Median duration between the first and the second SCT was six months (range: 3-24 months). Median duration between the relapse and the second SCT was 39 days (range: 22-60 days). All but one patient didnot receive induction chemotherapy due to the low probability of achieving complete remission (CR),and another patient didnot receive induction chemotherapy due to low blast percentage in bone marrow. Mean blast counts in bone marrow and peripheral blood were 39.3% and 22.1%, respectively. All but one patient were conditioned with fludarabine (25 mg/m2/day) from Day -8 to Day -4, with L-PAM (40 mg/m2/day) from Day -3 to Day -2, and with TBI (4Gy) on Day -1. Only FK506 was administered to patients as a graft versus host disease (GVHD) prophylaxis. Mean concentrations of FK506 during the first, second, third, and fourth 10-day period after CBT were 8.9, 8.9, 10.2, and 9.8 ng/ml, respectively. Median follow-up period was 12 months after transplantation in patients who survived. Six patients were alive at the last follow-up with a 1-year and 2-year OS rate of 72.7% and 36.4%, respectively. Five of these 6 patients have been maintaining CR. Four of the 5 patients maintaining CR were considered to be at an extremely high risk for relapse because they relapsed within 8 months (median: 5.5 months, range: 5 to 8 months) after the first SCT. These 4 patients have maintained CR with a median follow-up of 12 months (range: 7 to 32 months). The 2-year probabilities of transplant-related mortality (TRM), relapse-free survival (RFS), and relapse were 27.3%, 40.9%, and 42.9%, respectively. RIC-CBT without preceding remission induction therapy using a relatively low concentration of FK506 as a GVHD prophylaxis may be a promising therapeutic option for patients with AL who relapse shortly after the first transplantation. Age/Sex Disease Donor type of 1st SCT Preparative regimen of 1st SCT Time (months) from 1st SCT to relapse Time (days) from relapse to 2nd SCT Blast BM Blast PB Status last follow up Overall Survival (months) 53/F AML MUD TBI-CY 12 42 31.8% 3% death no relapse 3 42/M AML CB TBI-CY 5 37 49.4% 6% alive CR 32 40/F AML CB BU-CY-TBI 5 32 29.0% 81% death relapse 15 38/M AML MUD TBI-CY 21 28 64.8% 80% death no relapse 2 28/F AML SIB Flu-Mel-TBI 24 60 6.4% 1% alive CR 23 19/M ALL SIB TBI-CY 8 35 50.0% 49% death relapse 15 21/M ALL MUD TBI-CY 8 22 73.8% 1% alive CR 7 50/M AML MUD TBI-CY 5 39 9.0% 2% alive CR 9 45/F ALL SIB TBI-CY 6 41 57.8% 4% alive CR 15 55/F ALL(Ph1) SIB TBI-CY 4 41 51.2% 16% alive relapse 6 21/F AML Related TBI-CY 6 42 9.2% 0% death no relapse 3 Disclosures: No relevant conflicts of interest to declare.

The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group.

PURPOSE In an effort to maintain the excellent long-term results achieved with combination chemotherapy for good-prognosis germ cell carcinoma, but to reduce the toxicities encountered, a randomized trial was conducted comparing cisplatin and vinblastine with or without bleomycin. PATIENTS AND METHODS Two hundred eighteen assessable patients with a good prognosis were randomized to receive induction chemotherapy with cisplatin 100 mg/m2 intravenously (IV) day 1 and vinblastine 6 mg/m2 IV days 1 and 2 every 3 weeks (PV) with or without bleomycin 30 mg intramuscularly (IM) weekly (PVB) for a maximum of 12 weeks. Once maximum response was achieved, patients with a complete remission (CR) received two courses of consolidation chemotherapy, while those with residual abnormalities and normal tumor markers underwent surgical resection whenever possible. RESULTS Toxicities encountered in this study were clearly greater for those patients who received bleomycin, with significantly more leukopenia, thrombocytopenia, anemia, alopecia, and renal and pulmonary toxicities. The proportion of patients who achieved CR and had no evidence of disease (resection of all viable malignancy) was 89% for PV and 94% for PVB (P = .29). After a minimum of 4 years of follow-up, relapses have occurred in 7% of patients who received PV and 5% who received PVB. A total of five patients on each therapy arm were successfully treated with further salvage chemotherapy and surgery. Thus, deaths from progressive malignancy have occurred in 15% of patients on PV and 5% on PVB (P = .02), a rate that was partly offset by the higher proportion of toxic deaths with PVB (P = .06). CONCLUSION Despite the toxicities encountered with bleomycin in cisplatin-based combination chemotherapy for these patients, complete deletion of this drug compromises therapeutic efficacy.

High-dose versus low-dose vinblastine in cisplatin-vinblastine-bleomycin combination chemotherapy of non-seminomatous testicular cancer: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group.

Two hundred fourteen patients with disseminated non-seminomatous testicular cancer were randomized to receive induction chemotherapy with cisplatin, vinblastine, and bleomycin (PVB). The randomization was for vinblastine 0.4 mg/kg/cycle or 0.3 mg/kg/cycle. The complete response (CR) rates to both regimens were identical: 68% and 71%, respectively. In addition, there was no significant difference in disease-free and overall survival. There was a significant decrease in the incidence of WBC nadirs below 1,000/microL: 29% and 13%, respectively (P = .01). Of the non-hematologic toxicities, there was a significant reduction in the incidence of mucositis: 53% and 37%, respectively (P = .006). The major prognostic factor was tumor volume. This study confirms that vinblastine 0.3 mg/kg/cycle in PVB chemotherapy is as effective and less toxic than vinblastine 0.4 mg/kg/cycle.