CTNI-37. ISOEFFECTIVE HYPOFRACTIONATION FOR ELDERLY OR FRAIL PATIENTS WITH A NEWLY DIAGNOSED GLIOBLASTOMA: A POOLED INTERNATIONAL STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi67-vi68
Author(s):  
Haley Perlow ◽  
Michael Yang ◽  
Brett Klamer ◽  
Jennifer Matsui ◽  
Livia Marrazzo ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Phase 1 ◽  
Multivariable Analysis ◽  
Standard Of Care ◽  
Concurrent Chemotherapy ◽  
Newly Diagnosed ◽  
Observation Study ◽  
Phase Ii Studies ◽  
Survival Difference ◽  
Hypofractionated Radiation

Abstract PURPOSE The standard of care (SOC) for elderly or frail glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy. However, this regimen has a lower BED compared to the Stupp regimen, 60 Gy in 30 fractions. We hypothesize that isoeffective hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to standard of care. METHODS Elderly GBM patients treated with 52.5 Gy in 15 fractions were pooled from 2 phase II studies, 1 phase 1 and a prospective observation study. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Univariate and multivariate analyses were performed. RESULTS 62 newly-diagnosed patients were eligible for this analysis. Median follow-up was 10 months. The median OS and PFS was 10.3 and 6.9 mos, respectively. Patients with KPS ≥ 70 and < 70 had a median OS of 15.3 and 9.5 mos. No survival difference was seen between unmethylated and methylated patients with a median OS of 10.2 and 10.3 months, respectively. Multivariable analysis demonstrated that concurrent chemotherapy was an independent prognostic factor for improved PFS and OS. Grade 3 neurologic toxicity was seen in 2 patients (3.2%). CONCLUSION This is the first pooled, prospective analysis of elderly/frail GBM patients treated with dose-escalated hypofractionated radiation. Treatment was well tolerated and demonstrated excellent OS and PFS, exceeding that from prior elderly trials (Roa; 6.5 mo [poor KPS]/Perry; 9.3mo [good KPS]). This treatment regimen gives the elderly population an alternative to Stupp that is not de-escalating therapy. Future prospective trials are needed to validate these results.

The combination of venetoclax, lenalidomide, and rituximab in patients with newly diagnosed mantle cell lymphoma induces high response rates and MRD undetectability.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7505-7505
Author(s):  
Tycel Jovelle Phillips ◽  
Alexey Valeryevich Danilov ◽  
David Alan Bond ◽  
Alex Francisco Herrera ◽  
Kami J. Maddocks ◽  
...  
Keyword(s):  
Phase 1 ◽  
Safety Data ◽  
Standard Of Care ◽  
Primary Objective ◽  
Clinical Activity ◽  
Newly Diagnosed ◽  
Grade 5 ◽  
Unrelated Condition ◽  
Mantle Cell ◽  
Grade 3

7505 Background: MCL is a rare lymphoma without a standard of care but several regimens have demonstrated clinical activity, the majority based on traditional chemotherapy. We hypothesized that adding venetoclax (V) to R2 would be safe and effective in MCL pts irrespective of age, morphology or stage. Here we present safety and efficacy data from the on-going phase 1b study of R2 + V in pts with newly diagnosed MCL. Methods: This multi-center phase 1 study (NCT03523975) enrolled pts aged ≥18 yrs with untreated MCL. The primary objective was to characterize the safety and tolerability of R2 + V and determine the MTD. During induction (12 months (m)) pts received lenalidomide (L) 20 mg daily on day 1-21, Rituximab (R) was given weekly during c1 then on day 1 of every even cycle, V was escalated over 4 weeks to 400 mg beginning day 8. Each cycle is 28 days (d). The DLT period was 42 d beginning C1D8. In maintenance, R every 8 weeks for 36m, L at 10 mg or half of last dose during induction for 24 m and V for minimum 12 m. No pts have been transplanted. Pts with progression (PD) came off study. MRD was analyzed in parallel with scans during induction by clonoSEQ assay (Adaptive Biotechnologies). Results: As of Feb. 1st, 2021, we have enrolled all 28 planned pts on study. Pt characteristics/responses are summarized in Table. Among the 28 pts who have received at least one dose, the median treatment duration so far is 278d (IQR 170-560), with 24 pts still on treatment (Tx). 1 pt is off from a unrelated condition. All pts escalated to V 400 mg w/o any DLTs noted. Treatment-emergent adverse events (TEAEs) were reported in 100% of pts, and grade 3+ TEAEs were reported in 26 (93%) patients. The most common all-grade TEAEs (≥50% of pts), regardless of relationship to study Tx, were fatigue, neutropenia and diarrhea. Grade ≥3 TEAEs reported in ≥50% pts were neutropenia (68%) and thrombocytopenia (50%). No pts have withdrawn or d/c Tx due to AEs. There was one grade 5 event, in a non-evaluable pt, related to a PE that occurred prior to DLT period. In the 28 evaluable pts the ORR (CR/PR) was 96% (27/28 pts) with CR/CRu of 89%. Of the responding pts, two had PD, one w/ CR and one w/ PR. All pts with PD had baseline TP53 mutation. MRD testing was successful in all pts. At time of submission 20 of 28 (71%) were MRD - at 10-6. Conclusions: Interim results show that at the MTD the combination of V 400 mg daily, L 20 mg, with R is safe with a manageable toxicity profile and a high ORR and MRD - in pts with newly diagnosed MCL. Safety data is consistent with the AE profile noted for each drug without any unexpected or unique AEs. Updated results including BH3 profiling will be presented at the meeting. Clinical trial information: NCT03523975. [Table: see text]

CTIM-13. PHASE 1 CLINICAL TRIAL OF ONCOLYTIC VIRAL IMMUNOTHERAPY WITH CAN-2409 + VALACYCLOVIR IN COMBINATION WITH NIVOLUMAB AND STANDARD OF CARE (SOC) IN NEWLY DIAGNOSED HIGH-GRADE GLIOMA (HGG)

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi52-vi52
Author(s):  
Patrick Wen ◽  
Laura Aguilar ◽  
Xiaobu Ye ◽  
David Reardon ◽  
Wenya Linda Bi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Phase 1 ◽  
Standard Of Care ◽  
Toxic Metabolite ◽  
Diffuse Astrocytoma ◽  
Newly Diagnosed ◽  
Phase 1 Clinical Trial

Abstract BACKGROUND CAN-2409 is a replication-deficient adenovirus that delivers HSV thymidine kinase to cancer cells, resulting in local conversion of orally administered valacyclovir into a toxic metabolite. Previously, a phase 1b/2 clinical trial of CAN-2409 combined with standard-of-care (SOC) demonstrated safety and improved survival in HGG patients. Addition of CAN-2409 to nivolumab has the potential to activate locally recruited lymphocytes and teach them to recognize tumor neoantigens, changing the ‘cold’ immunosuppressive tumor microenvironment, and synergizing with the activity mediated by immune checkpoint inhibitors. This notion is supported by preclinical experiments showing that the combination of CAN-2409 with anti-PD1 therapy was more effective than either treatment alone. METHODS This ongoing phase 1 clinical trial evaluates safety and initial efficacy of CAN-2409 combined with nivolumab and SOC in newly diagnosed HGG. CAN-2409 is injected during neurosurgery into the tumor bed, followed by 14-days of valacyclovir. Radiation starts within 8 (+/-4) days of surgery. Temozolomide is administered to MGMT-methylation positive patients only. Nivolumab is given every 2 weeks, up to 52-weeks. Deep immune profiling studies are ongoing and initial results will be available shortly. RESULTS From February 2019 to March 2021, 41 patients were enrolled and 35 were evaluable for safety from the combination of CAN-2409, nivolumab and SOC: 24 male and 11 female; 34 glioblastoma, 1 diffuse astrocytoma; 33 IDH-wildtype, 2 IDH-mutant; 15 MGMT-methylated, 20 unmethylated. Median age was 62-years (range 28-79), median KPS 90 (range 80-100). With 13 months median follow-up, no unexpected serious adverse events were observed, and 23 patients are still alive. The most frequent possibly related adverse events (>10%) were nausea, fatigue, fever, headache, and increased ALT. CONCLUSIONS The combination of CAN-2409 + nivolumab + SOC was well tolerated. Clinical follow-up and extensive biomarker analyses will provide a better understanding of the therapeutic potential of this approach.

VELCADE/Dexamethasone (Vel/D) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantion (ASCT) in Newly Diagnosed Multiple Myeloma (MM): Updated Results of the IFM 2005/01 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 450-450 ◽  
Author(s):  
Jean Luc Harousseau ◽  
Claire Mathiot ◽  
Michel Attal ◽  
Gerald Marit ◽  
Denis Caillot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Standard Of Care ◽  
Response Assessment ◽  
Primary Objective ◽  
Induction Treatment ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Phase Ii Studies ◽  
The Impact

Abstract Introduction. ASCT is considered the standard of care for younger patients (pts) with MM. The benefit of ASCT is at least partly related to an increase in Complete Remission (CR) plus Very Good Partial Remission (VGPR) rate. One way to increase the CR rate is to improve the induction treatment prior to ASCT. Several phase II studies with Vel in combination as induction treatment yielded promising CR rates. We have previously tested the Vel/D combination with Vel 1.3mg/m2 d1,4,8,11 with 40mg/d d1–4, d 9–12 for 4 consecutive 21d cycles (D only on d1–4 during cycles 3–4) (Harousseau et al Haematologica 2006). Methods. In July 2005, the IFM initiated a randomized Phase II trial comparing Vel/D with VAD as induction treatment prior to ASCT in pts with newly diagnosed MM up to the age of 65.This IFM 2005/01 was closed for accrual in January 2007 after having recruited 482 patients. The primary objective was the CR (negative immunofixation) plus n-CR (negative electrophoresis) after 4 cycles. The second question was to evaluate the impact of a consolidation with 2 cycles of DCEP (D, Cyclophosphamide, Etoposide, Platinum). At diagnosis pts were randomized between 4 arms (A1:4 cycles of VAD, A2: 4 cycles of VAD + 2 cycles of DCEP, A3:4 cycles of Vel/D, A4:4 cycles of Vel/D + 2 cycles of DCEP). Randomization was stratified according to β2-microglobulin and del 13 by FISH analysis. Stem cell collection was performed between cycle 3 and 4 after G-CSF priming (10μg/kg x 6d). ASCT was prepared by melphalan 200mg/m2. Results. As of Aug 2007, data from the first consecutively enrolled 222 pts have been analyzed (A1:54,A2:56,B1:55,B2:57). In the VAD arms (A1+A2),88% of pts received the planned 4 courses versus 94% in the Vel/D arms (B1+B2). In arm A2,87.5% of pts received the 2 cycles of DCEP versus 82% in arm B2. ASCT was performed in 94% of evaluable pts in arms A1+A2 and in 92% in arms B1+B2. The number of SAE was the same in the VAD and the Vel/D arms. The incidence of grade 3–4 averse events was also comparable. However the proportion of pts with neurological symptoms (all grades) during induction treatment was higher with Vel/D (36% versus 11%). Response assessment is available for 208 pts (100 VAD, 108 Vel/D). The results are shown in the table (intent-to-treat analysis). Consolidation with DCEP did not increase the CR rate (16% pre-ASCT both in arms A1+B1 and in arms A2+B2). Conclusion. This analysis not only confirms that the post-induction CR rate is increased by Vel/D compared to VAD (Harousseau ASH 2006) but also shows that this benefit translates in higher CR+VGPR rates after ASCT. Longer follow-up is needed to demonstrate that this better tumor reduction induces longer PFS and OS. Currently 1-year PFS and OS rates are respectively 90% and 95% with VAD, 93% and 97% with Vel/D. Updated results will be presented at the meeting.

CTNI-19. CONCURRENT CHEMORADIATION AND TUMOR TREATING FIELDS (TTFields, 200 kHz) FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MAY INCREASE THE RATE OF DISTANT RECURRENCE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi63-vi63
Author(s):  
Ayesha S Ali ◽  
Muneeb Niazi ◽  
Voichita Bar-Ad ◽  
Maria Werner-Wasik ◽  
David Andrews ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Synergistic Effects ◽  
Secondary Analysis ◽  
Standard Of Care ◽  
Distant Recurrence ◽  
Concurrent Chemoradiation ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract INTRODUCTION: Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) along with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. Secondary analysis of EF14 trial demonstrated TTFields treatment may increase the rate of distant recurrence. We report our experience evaluating areas of progression in our pilot clinical trial of concurrent chemoradiation with TTFields. METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from primary enhancing lesion. RESULTS: A total of 30 patients were enrolled on the trial. Twenty were male, and ten were female, with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 11.6 months (1.7-22.1 months). Twenty (66.7%) patients had an unmethylated MGMT promotor status and ten (33.3%) patients had a methylated promoter status. Twenty patients (66.7%) had progression, with median PFS of 9.1 months (range 1.6 to 12.9 months). Five patients (26%) of patient presented with distant recurrence, with median distance from primary lesion of 5.1 cm (2.26-9.12 cm). One infratentorial progression was noted. Another patient transferred care and location of progression is unknown. CONCLUSIONS: Concurrent chemoradiation with TTFields for patients with newly diagnosed glioblastoma may have increased incidence of distant recurrence. This finding is suggestive of improved local control of primary site. Further data are needed to validate this finding.

Scalp-sparing radiation with concurrent temozolomide and tumor treating fields (SPARE) for patients with newly diagnosed glioblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2056-2056
Author(s):  
Ryan C Miller ◽  
Andrew Jehyun Song ◽  
Ayesha Ali ◽  
Voichita C Bar-Ad ◽  
Nina Leyson Martinez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Radiation Treatment ◽  
Synergistic Effects ◽  
Standard Of Care ◽  
Treatment Interruption ◽  
Newly Diagnosed ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Dose Constraints ◽  
Topical Medications

2056 Background: Standard of care for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our clinical trial evaluating safety and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. Methods: This is a single arm pilot study. Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of TTFields concurrent with chemoradiation in patients with newly diagnosed glioblastoma. Results: A total of 30 patients were enrolled in the trial. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). Median follow-up was 8.9 months (range 1.6 to 21.4 months). Twenty (66.7%) patients had unmethylated MGMT promotor status and ten (33.3%) patients had methylated promoter status. Median time from surgery to radiation was 34 days (26 to 49 days). Scalp dose constraints were achieved for all patients, with the mean dose having a median value of 8.3 Gy (range 4.3 to 14.8 Gy), the D20cc median was 26.1 Gy (range 17.7 to 42.8 Gy), and the D30cc median was 23.5 Gy (range 14.8 to 35.4 Gy). Skin adverse events (AEs; erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). Nineteen patients (63.3%) had progression, with a median PFS of 7.6 months (range 1.6 to 12.7 months). Overall survival was not reached. Conclusions: Concurrent TTFields (200 kHz) with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation. Clinical trial information: NCT03477110.

CTIM-08. SAFETY, EFFICACY, AND SURVIVAL RESULTS FROM A PHASE 1 STUDY OF THE ONCOLYTIC ADENOVIRUS DNX-2401 FOLLOWED BY STANDARD OF CARE RADIOTHERAPY FOR NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi50-vi51
Author(s):  
Jaime Gállego Pérez-Larraya ◽  
Marc Garcia-Moure ◽  
Ana Patiño-García ◽  
Marisol González-Huarriz ◽  
Jasper Van der Lugt ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase 1 ◽  
Standard Of Care ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Oncolytic Adenovirus ◽  
Newly Diagnosed ◽  
Pontine Glioma ◽  
Serious Adverse Events ◽  
Tumor Biopsy ◽  
Grade 3

Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is the most lethal pediatric brain tumor. Median overall survival (OS) with standard of care radiation therapy (RT) is approximately 8-10 months and 2-year survival is < 10%. A Phase 1 single-center study was conducted to evaluate the oncolytic adenovirus, DNX-2401 (tasadenoturev), followed by RT for DIPG. METHODS Newly-diagnosed DIPG patients 1-18 years old received a tumor biopsy through the cerebellar peduncle followed by intratumoral injection of 1e10 – 5e10 vp DNX-2401 and conventional RT 1-3 weeks later. RESULTS Subjects were enrolled (n=12) from December 2017 to January 2020 and had a median age of 9 years (range 3-18) and Lansky/Karnofsky performance scores of 90-100 (n=4; 33%) or 70-80 (n=8; 67%). Genetic assessment was completed for 11 subjects (92%) and histone 3 K27M mutations were identified in 10 subjects, including H3F3A (n=8), HIST2H3C (n=1), and HIST1H3B (n=1); 1 subject was H3 wildtype (n=1). TP53 mutations were identified in 5 subjects (42%). DNX-2401 was administered followed by RT (n=11; 92%). No dose-limiting toxicities were observed and the treatment regimen was well-tolerated. The most commonly reported adverse events (≥ 5 subjects), regardless of study drug relationship, include asthenia, headache, vomiting, pyrexia, and neurological deterioration. Three serious adverse events were reported including grade 3 abdominal pain, grade 3 lymphopenia, and grade 3 clinical deterioration. Tumor reductions were reported for 9 subjects (75%), including 2 confirmed (17%) and 2 unconfirmed (17%) responses per RAPNO criteria. As of the data cutoff, median OS is 19.7 months and OS-24 is 32% with follow-up ongoing for 3 subjects (26.9, 25.6, 13.7 months). CONCLUSIONS DNX-2401 followed by RT can be safely administered to DIPG. Survival outcomes are encouraging, thus warranting further evaluation in a Phase 2 study.

Increased Number of High Dose Methotrexate Cycles and the Addition of Rituximab Is Associated with Better Outcomes in a Large Primary CNSL Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4125-4125
Author(s):  
Prakirthi Yerram ◽  
Samantha Nicole Reiss ◽  
Lisa Modelevsky ◽  
Lauren Schaff ◽  
Anne Reiner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Multivariable Analysis ◽  
Standard Of Care ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Historical Cohort ◽  
Dose Methotrexate

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive primary brain tumor confined to the brain, eyes, and cerebrospinal fluid. Over the past few decades, prognosis for PCNSL has significantly improved due to the standard use of high dose methotrexate (MTX) containing treatment regimens. However, it remains unclear if the number of MTX doses and the addition of rituximab has an impact on clinical outcomes. The recent HOVON 105/ALLG NHL 24 study questioned the role of rituximab in the first line setting when combined with a MTX based polychemotherapy using only 4 doses of MTX and 6 doses of rituximab. Over the last 30 years, standard of care at Memorial Sloan Kettering Cancer Center (MSKCC) has evolved, allowing the comparison of patients receiving different numbers of MTX doses and those treated with and without rituximab. The purpose of this study was to describe clinical outcomes based on standard of care treatment changes. Methods: This single-center retrospective IRB approved study at MSKCC included patients with immunocompetent PCNSL, age ≥18 years and diagnosed between 1/1983-11/2017. Patients were identified through a departmental database and electronic medical record. The primary objective was to describe overall survival (OS) based on common prognostic markers such as age, KPS, MSKCC prognostic score class (RPA I- III), use of rituximab, and number of methotrexate cycles. Overall survival was calculated from the date of diagnosis to death or last follow-up using Kaplan-Meier methodology. When examining effect of MTX on OS, OS was calculated from date of last MTX cycle until death or last follow-up. Univariable and multivariable analysis for prognostic factors were analyzed using Cox proportional hazards regression. Results: Five hundred and forty-six patients with newly diagnosed PCNSL were identified. Median age at diagnosis was 62 (range 19 to 90), median KPS was 70 (range 10 to 100), and 282 (52%) were men. In total, 472 patients (86.4%) received high dose MTX. Of 460 with known number of MTX cycles, 95 (20.7%) received 1-4 cycles and 365 (79.3%) received ≥5 cycles (5 cycles: 189, 41.1%, 6 cycles: 24, 5.2%, 7 cycles: 74, 16.1%, 8+ cycles: 78, 17%). Rituximab was given to 231 (42.3%). Three hundred and ten (56.8%) patients, treated before 2006, had been reported previously (historic cohort) and 236 (43.2%) served as contemporary cohort. Median OS of the entire population was 4.7 years (95% CI: 3.8-5.7); 3.3 years (95% CI: 2.8-4.1) in the historic and 8.1 years (95% CI: 6.6-no upper limit) in the contemporary cohort. Five-year OS was 40.3% (95% CI: 35.1-46.2) for the historical cohort and 61.8% (95% CI: 55.0-69.5) for the contemporary cohort. Median OS in the contemporary cohort improved in all RPA classes in comparison to patients treated before 2006 (RPA I: not yet reached vs 9.2 years; RPA II: 7.6 years vs 3.5 years; RPA III 2.8 years vs 1.0 year) (Fig. 1). For the historical cohort compared to the contemporary cohort, five-year OS changed from 62.8% to 91.0% in RPA I, 42.0% to 63.0% in RPA II, and 16.3% to 36.9% in RPA III. Patients receiving ≥ 6 cycles of MTX had a better clinical outcome (median OS from last MTX cycle: 7.8 years versus 4.3 years; HR 0.68 (95% CI (0.51 - 0.91), p=0.0085) on multivariable analysis adjusted for age, KPS, sex, RPA classes Additionally, the stratification of rituximab further elucidated the association between MTX cycles and OS, such that in patients receiving rituximab, those treated with ≥ 6 cycles of MTX experienced longer median OS compared to patients receiving < 6 cycles of MTX (13.0 years vs 9.4 years, p=0.001). Furthermore, in patients receiving ≥ 6 cycles of MTX, there was a survival benefit seen in patients who received rituximab compared to those who did not receive rituximab (13.02 years vs 1.61 years, p<000.1) (Fig.2). Conclusions: Overall survival for newly diagnosed PCNSL has improved significantly over the last few decades regardless of age, KPS, RPA class. Patients seem to benefit with the addition of rituximab and when receiving 6 or more cycles of MTX. Disclosures Grommes: BTG: Consultancy; Kite: Consultancy; Squipps: Speakers Bureau.

QOLP-20. DIETARY, ACTIVITY, AND QUALITY OF LIFE METRICS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA IMPLEMENTING A KETOGENIC DIET: RESULTS OF A PHASE 1 CLINICAL TRIAL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi187-vi187
Author(s):  
Thomas Nelson ◽  
Gillian Gresham ◽  
Amelia Welborn ◽  
L J Amaral ◽  
Brandon Noorvash ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ketogenic Diet ◽  
High Intensity ◽  
Phase 1 ◽  
Standard Of Care ◽  
Activity Levels ◽  
Newly Diagnosed ◽  
Activity Data ◽  
Phase 1 Trial

Abstract BACKGROUND Emerging evidence suggests that a ketogenic diet (KD) may limit neoplastic growth, but limited data exist regarding the effect of KD on daily activity, cognition, and health-related quality-of-life (HRQOL) for patients with glioblastoma. METHODS Newly diagnosed GBM patients participating in a single-arm phase 1 trial of a 16-week KD plus standard-of-care measured BID blood glucose and ketone levels (Keto-Mojo), captured continuous activity data (Fitbit), and completed quality-of-life (QLQ30) surveys and Montreal Cognitive Assessments (MoCA) at baseline, Week 8, and study end (up to 16 weeks). NCT03451799. RESULTS All patients (n = 14; 57% female; median age 55 years) maintained blood ketones above 0.3 mM > 50% of study duration (mean per-patient days in ketosis = 87%). Mean glucose (mg/dl) and ketone levels decreased through the study – Weeks 1/2: glucose 94.9 (SD:16.5), ketones 1.44 (SD:5.82); Weeks 3/4: glucose 94.1 (SD:12.9), ketones 1.34 (SD:0.9); Final two weeks: glucose 92.3 (SD:13.3), ketones 1.13 (SD:0.7). On average, patients walked 6,836 steps/day (SD:5,129), spending 14.3 hours sedentary (SD:6.45) and 43.6 minutes (SD:60.4) in high-intensity activity. Sleep duration was 6.8 hours (SD:2.26). Patients (n = 9) with OS > 14.6 mo from diagnosis demonstrated greater minutes of high-intensity activity (58.2 vs 20.7, p = 0.001), downtrending glucose (p = 0.001), and higher ketone levels (1.40 vs 1.11, p = 0.026). Activity data corroborated the tolerability of KD with stable-to-increased activity by study end. MoCA scores were stable from baseline (mean 23.4/30, SD:4.16) to study end (mean 24.8/30, SD:7.12; p = 0.38). When viewed as a composite score, HRQOL was stable-to-improving in 10/14 patients at Week 8 and EOS. CONCLUSION The use of wearable technology and at-home testing allowed for remote monitoring of activity and diet adherence. Good adherence and stable HRQOL and activity levels were observed in this phase 1 trial.

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