scholarly journals INNV-28. TEMOZOLOMIDE IN RENAL DYSFUNCTION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii122-ii122
Author(s):  
Kayla Garzio ◽  
Kelly McElroy ◽  
Stuart Grossman ◽  
Matthias Holdhoff ◽  
Byram Ozer ◽  
...  
Keyword(s):  
Renal Function ◽  
Medical Records ◽  
Alkylating Agent ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Grade ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Experienced Grade

Abstract BACKGROUND Temozolomide (TMZ) is a cytotoxic DNA alkylating agent. It is the only chemotherapy known to improve survival in patients with high grade astrocytomas. The active alkylating species, methylhydrazine, is not recovered in the urine and thus renal function is not expected to affect clearance of this agent. It has never been formally evaluated in adults with eGFR < 36 mL/min/1.73 m2, and it is often recommended to administer with caution, dose reduce, or withhold therapy. However, lacking other effective therapies, we have elected to administer TMZ at full dose to these patients. This IRB approved retrospective study was conducted to evaluate the safety of this practice. METHODS The primary endpoint was to characterize the incidence and severity of thrombocytopenia in patients with renal impairment defined as eGFR < 60 mL/min/1.73 m2 who received TMZ for the treatment of their high grade gliomas (HGG) or primary CNS lymphoma (PCNSL). Secondary endpoints included incidence and severity of neutropenia, lymphocytopenia, hepatotoxicity, and number of cycles administered. Medical records were reviewed for adult patients with HGG or PCNSL treated with TMZ from October 1, 2016-September 30, 2019. RESULTS Thirty-four patients met criteria for inclusion. Of the 7 patients with eGFR < 36 mL/min/1.73m2, 33/34 cycles (97%) were completed successfully without grade 3–4 thrombocytopenia. No patients experienced grade 3–4 neutropenia, and grade 3–4 lymphocytopenia occurred in 5 cycles (15%). One patient required discontinuation of TMZ 7 days prior to completion of radiation due to thrombocytopenia. CONCLUSION The side effect profile from TMZ administered to patients with eGFR < 36 mL/min/1.73 m2 appears to be similar to that of patients with normal renal function. This is not an unanticipated finding given what is known about the metabolism of the drug.

Randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for muscle invasive urothelial bladder cancer (MIUBC): Preliminary results of the GETUG/AFU V05 VESPER trial on toxicity and pathological responses.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 437-437 ◽  
Author(s):  
Stephane Culine ◽  
Gwenaelle Gravis ◽  
Aude Flechon ◽  
Michel Soulie ◽  
Laurent Guy ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Perioperative Chemotherapy ◽  
Urothelial Bladder ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Dose Dense ◽  
Number Of Cycles

437 Background: The optimal perioperative chemotherapy regimen for patients (pts) with MIUBC is not defined. Methods: Between February 2013 and February 2018, 494 pts were randomized in 28 French centres and received either 4 cycles of GC every 3 weeks or 6 cycles of dd-MVAC every 2 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). The primary endpoint was the progression-free survival at 3 years. Secondary endpoints included toxicity, pathological responses and overall survival. Results: In the neoadjuvant group, 218 pts received dd-MVAC and 219 pts GC. The median number of cycles was 6 (0-6) and 4 (1-4), respectively. 60% of pts received 6 cycles in the dd-MVAC arm, 84% received 4 cycles in the GC arm. 199 pts (91%) and 198 (90%) pts underwent surgery, respectively. Complete pathologic responses (ypT0pN0) were observed in 84 (42%) and 71 (36%) pts, respectively (p=0.02). An organ-confined status (<ypT3pN0) was obtained in 154 (77%) and 124 (63%) pts, respectively (p=0.002). In the adjuvant group (57 pts), the median number of cycles was 5 (1-6) and 4 (1-4), respectively. 40% of pts received 6 cycles in the dd-MVAC arm, 60% received 4 cycles in the GC arm. Most of CTCAE grade ≥ 3 toxicities concerned hematological toxicities. At least one of these where reported for 125 (50%) pts in the dd-MVAC group and 134 (54%) pts in the GC group (p=NS). Gastrointestinal (GI) grade ≥ 3 disorders were more frequently observed in the dd-MVAC arm (p<0.0001) as well as grade ≥ 3 asthenia (p<0.00001). Four deaths (3 in the dd-MVAC) occurred during chemotherapy. Conclusions: Complete pathological responses and organ-confined status were more frequently observed in the dd-MVAC arm. Toxicity was manageable with more severe asthenia and GI side effects in the dd-MVAC arm. Clinical trial information: 2012-000563-25.

Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients (pts) with untreated advanced gastric cancer (AGC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 111-111
Author(s):  
T. E. Nakajima ◽  
T. Satoh ◽  
K. Muro ◽  
Y. Yamada ◽  
Y. Shimada ◽  
...  
Keyword(s):  
Phase I ◽  
Safety Profile ◽  
Phase I Study ◽  
Potent Inhibitor ◽  
Japanese Patients ◽  
First Line ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
The Individual ◽  
Experienced Grade

111 Background: Cediranib (AZD2171) is an oral, highly potent inhibitor of VEGF signalling with activity versus all three VEGFRs and c-Kit. Combination therapy with cisplatin + oral fluoropyrimidine is commonly used as first-line treatment for AGC. This phase I study assessed cediranib in combination with cisplatin/S-1 or cisplatin/capecitabine in Japanese pts with previously untreated AGC. Methods: Eligible pts received cediranib 20 mg/day and either cisplatin 60 mg/m2 iv, day 1 + S-1 40–60 mg bd, days 1–21, q5w (Arm A) or cisplatin 80 mg/m2 iv, day 1 + capecitabine 1000 mg/m2 bd, days 1–14, q3w (Arm B). The primary endpoint was safety and tolerability. Secondary endpoints included assessment of steady-state pharmacokinetics (PK) of cediranib and chemotherapy alone and in combination. Preliminary efficacy was an exploratory objective. Adverse events (AEs) were evaluated according to CTCAE v3.0. Results: Between Aug–Dec 2009, 14 pts (median age, 60.5 [27–72] years; male, n = 9; PS 0/1, n = 7/7) were recruited to Arm A (n = 6) or Arm B (n = 8). The safety profile in both arms was consistent with that of the individual agents. There were no unexpected toxicities. All pts experienced ≥1 AE. Dose-limiting toxicities were reported in 1 pt in Arm A (decreased appetite) and 1 pt in Arm B (decreased appetite, fatigue, hyponatremia). The most common AEs in Arm A were decreased appetite, fatigue, nausea, diarrhoea, decreased weight and neutropenia (all n = 5; 83%), and decreased appetite, fatigue, nausea (all n = 8; 100%) and constipation (n = 7; 88%) in Arm B. Five (83%) pts in Arm A and 6 (75%) in Arm B experienced grade ≥ 3 AEs. Grade 3 AEs in > 1 pt were neutropenia (n = 3) in Arm A and hypokalaemia (n = 3), neutropenia, hyponatraemia and fatigue (all n = 2) in Arm B. Grade 4 syncope was reported in 1 pt in Arm A; this resolved on the same day it was observed. Preliminary efficacy and PK data will be presented. Conclusions: Cediranib 20 mg plus cisplatin/S-1 or cisplatin/capecitabine was generally well tolerated and considered suitable for further evaluation in pts with AGC. The safety profile of each regimen was comparable with the individual agents. No new toxicities were identified. [Table: see text]

A phase I, open-label, nonrandomized, pharmacokinetic study of trifluridine/tipiracil (TAS-102) in Chinese patients with solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14079-e14079
Author(s):  
Xicheng Wang ◽  
Jianfeng Zhou ◽  
Yan Li ◽  
Yuping Ge ◽  
Yanping Zhou ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase 1 ◽  
Chinese Patients ◽  
Open Label ◽  
Significant Difference ◽  
Inactive Metabolite ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Experienced Grade ◽  
Clinical Trial Information

e14079 Background: Trifluridine/tipiracil (TAS-102) is an oral combination of an antineoplastic thymidine-based nucleoside analog, trifluridine (FTD), and the thymidine phosphorylase inhibitor, tipiracil (TPI). Trifluridine/tipiracil is demonstrated as a valid treatment choice for Asian and Western patients (pts) with metastatic colorectal cancer refractory or intolerant to standard chemotherapies in earlier studies. Its pharmacokinetic (PK) profile was also investigated in American and Japanese phase 1 studies, but never in Chinese pts. This study was conducted to investigate the PK profile of Trifluridine/tipiracil in a Chinese population with solid tumors. Methods: Pts who has responded poorly to existing standard treatment received Trifluridine/tipiracil (35 mg/m2/dose), orally BID, on days 1-5 and days 8-12 every 4 weeks until one of discontinuation criteria was met. Blood samples for PK analysis of FTD (the active compound), fluorothymine (FTY, inactive metabolite) and TPI were collected after single and multiple doses of Trifluridine/tipiracil on days 1 and 12 of cycle 1. The safety, tolerability, and antitumor activity of Trifluridine/tipiracil were also assessed as secondary endpoints. Results: A total of 15 pts were administered Trifluridine/tipiracil and analyzed for PKs. The PKs of FTD, FTY, and TPI in Chinese pts were comparable to those in Japanese pts. Compared with American pts, although the AUC0-t of TPI on day 12 was significantly lower in Chinese pts, the Cmax and AUC0-t of FTD were not significantly different. Thirteen (86.7%) pts reported treatment-emergent adverse events (TEAEs), and eight (53.3%) pts experienced grade 3 TEAEs, of which anemia and fatigue were most frequently (≥10% of patients) reported. Grade 4 or 5 TEAEs were not observed. Conclusions: The PKs of Trifluridine/tipiracil in Chinese pts were comparable to those in Japanese pts. The exposure of FTD was showed without significant difference between Chinese, Japanese and American pts. Trifluridine/tipiracil was well-tolerated in Chinese pts and had the similar safety profile in comparison with previous studies. Clinical trial information: NCT02261532.

Impact of renal function on the efficacy and safety of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 301-301
Author(s):  
Satoshi Kobayashi ◽  
Makoto Ueno ◽  
Gakuto Ogawa ◽  
Akira Fukutomi ◽  
Masafumi Ikeda ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Adverse Reactions ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Efficacy And Safety ◽  
Concurrent Radiotherapy ◽  
Secondary Endpoints ◽  
Grade 3

301 Background: S-1 is an oral agent consisting of a mixture of tegafur which is a prodrug of 5-fluorouracil (5-FU), 5-chloro-2,4-dihydroxypyrimidine (DHP) and potassium oxonate. Serum concentration of 5-FU increases in case of renal dysfunction due to decrease of DHP excretion into urine. The aim of this study was to evaluate the influence of renal function to the efficacy and safety of S-1 with concurrent radiotherapy (RT) for locally advanced pancreatic cancer (LAPC). Methods: This study was an integrated exploratory analysis of JCOG1106 and LAPC- S1RT, in which pts with LAPC received RT (50.4Gy/28 fr over 5.5 weeks) and concurrent S-1 (40 mg/m2/dose, bid. on the day of irradiation). Eligibility criteria for this study were pts who received both irradiation and S-1 at least once without induction chemotherapy, and who had creatinine clearance (CCr) ≥ 50 ml/min at the time of registration. We assigned pts into high (≥ 80 ml/min) and low (< 80 ml/min) CCr groups. The primary endpoint was the incidence of ≥ Grade 3 adverse reactions (ARs). Secondary endpoints were the incidence of ≥ Grade 2 gastrointestinal ARs (GI-ARs) defined as anorexia, nausea, vomiting, diarrhea and mucositis oral, relative dose intensity of S-1, CA19-9 response, progression-free survival, and overall survival. Results: Fifty and 59 pts were included in this study from JCOG1106 and LAPC-S1RT, respectively. Median age was 65 years old (range: 31–80), and 57 pts were male. Median CCr was 80.4 ml/min. High CCr group included 57 pts and the median was 97.5 ml/min (range 80.0–194.6), and low CCr group included 52 pts and the median was 64.4 ml/min (range 50.0–78.3). Low CCr group tended to have more ≥ Grade 3 ARs and ≥ Grade 2 GI-ARs compared to high CCr group (30.8% vs. 15.8% and 51.9% vs. 36.8%). However, no evident tendencies were observed in other secondary endpoints. Multivariable analysis showed risk ratio of low CCr group for ≥ G3 ARs was 1.493 [95% CI: 0.710–3.145], although risk ratio of females was 2.486 [95% CI: 1.043–5.924]. Conclusions: Our study indicated that renal dysfunction may increase adverse reactions in the treatment of S-1 with concurrent RT for LAPC, and we should pay attention to renal function and consider for dose reduction.

Enhanced Delivery of Rituximab In Combination with Methotrexate-Based Blood-Brain Barrier Disruption for Patients with Newly Diagnosed Primary CNS Lymphoma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2792-2792 ◽  
Author(s):  
Nancy D. Doolittle ◽  
Dale F. Kraemer ◽  
Cynthia Lacy ◽  
Rose Marie Tyson ◽  
Edward A. Neuwelt
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Primary Cns Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
Newly Diagnosed ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
Grade 3

Abstract Abstract 2792 Introduction: Primary CNS lymphoma (PCNSL) is a rare, aggressive, primarily large B-cell lymphoma confined to the CNS and/or eyes at presentation. High-dose (HD) methotrexate (MTX) - based chemotherapy is standard of care in PCNSL and when combined with enhanced delivery results in extended survival without cognitive loss. The addition of rituximab to HD MTX regimens for B-cell PCNSL is widely used primarily by analogy to the positive results attained in systemic B-cell lymphomas. However, recent pre-clinical and clinical use of single agent rituximab provides stronger rationale. Efficacy has been shown using single agent rituximab in nude rats with intracerebrally implanted MC116 human B-cell lymphoma cells, and in patients with recurrent PCNSL by using 111In-ibritumomab to assess delivery and 90Y-ibritumomab to assess efficacy. Next, safety and efficacy of enhanced delivery of rituximab with MTX-based blood-brain barrier disruption (BBBD) was shown in patients with recurrent PCNSL. Based on these results, we treated patients with newly diagnosed PCNSL with rituximab in combination with MTX-based BBBD. Methods: IRB permission was obtained to retrospectively evaluate patients with newly diagnosed B-cell PCNSL, treated with rituximab in combination with MTX-based (intra-arterial [i.a.]) BBBD chemotherapy as first-line treatment. Treatment consisted of MTX (2500mg/day, i.a.) and carboplatin (200mg/m2/day, i.a.) with BBBD, for 2 consecutive days every 4 weeks for up to one year. Rituximab (375mg/m2, i.v.) was given every 4 weeks, 12 hours prior to the MTX with BBBD treatment. Objective response rate, progression free survival (PFS), overall survival (OS), and toxicities were evaluated. Results: Twelve patients (7 female, 5 male) were treated between April 2003 and October 2008. The median age was 65 years (min 49, max 75); 10 patients were older than 60 years. The median Karnofsky Performance Score (KPS) prior to treatment was 55 (min 20, max 80). All patients had brain parenchyma involvement at presentation. Additionally, CSF cytology was positive in 2 patients and one patient had ocular involvement. One patient with pre-existing cardiac disease died 2 weeks after initiation of MTX without BBBD due to myocardial infarction and was not evaluable for response. The overall response rate was 83% (7 CR, 1 CRU, 2 PR, 1 SD). The median PFS was 3.47 years (95% CI: 0.42, not yet attained) and the 2-year PFS in this cohort is 73%. The median OS was 4.42 years (95% CI: 0.28, not yet attained). Eight patients who attained CR or CRU were alive at data-cut-off; 6 of the 8 patients remain in CR 2 years or more after diagnosis. The most frequent toxicities were hematologic. Eight (67%) patients developed grade 3 or 4 hematologic toxicity and 7 (58%) developed grade 3 infection. Conclusions: We previously reported a 2-year PFS of 50% with 25% survival at 8.5 years in 149 newly diagnosed PCNSL patients treated with MTX-based BBBD without rituximab. The addition of rituximab shows manageable toxicity and provides sustained duration of CR in newly diagnosed PCNSL, with 10 of 12 patients over 60 years old and a median KPS of 55. These pilot data suggest the 2-year PFS may be increased to 70% or more with the addition of rituximab to MTX-based BBBD chemotherapy. A multi-center phase II prospective study is underway. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227

2016 ◽  
Vol 34 (14) ◽  
pp. 1620-1625 ◽  
Author(s):  
Jon Glass ◽  
Minhee Won ◽  
Christopher J. Schultz ◽  
Daniel Brat ◽  
Nancy L. Bartlett ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Maximum Tolerated Dose ◽  
Primary Phase ◽  
Cns Lymphoma ◽  
Brain Radiotherapy ◽  
Grade 3

Purpose This study investigated the treatment of primary CNS lymphoma with methotrexate, temozolomide (TMZ), and rituximab, followed by hyperfractionated whole-brain radiotherapy (hWBRT) and subsequent TMZ. The primary phase I end point was the maximum tolerated dose of TMZ. The primary phase II end point was the 2-year overall survival (OS) rate. Secondary end points were preirradiation response rates, progression-free survival (PFS), neurologic toxicities, and quality of life. Patients and Methods The phase I study increased TMZ doses from 100 to 150 to 200 mg/m2. Patients were treated with rituximab 375 mg/m2 3 days before cycle 1; methotrexate 3.5 g/m2 with leucovorin on weeks 1, 3, 5, 7, and 9; TMZ daily for 5 days on weeks 4 and 8; hWBRT 1.2 Gy twice-daily on weeks 11 to 13 (36 Gy); and TMZ 200 mg/m2 daily for 5 days every 28 days on weeks 14 to 50. Results Thirteen patients (one ineligible) were enrolled in phase I of the study. The maximum tolerated dose of TMZ was 100 mg/m2. Dose-limiting toxicities were hepatic and renal. In phase II, 53 patients were treated. Median follow-up for living eligible patients was 3.6 years, and 2-year OS and PFS were 80.8% and 63.6%, respectively. Compared with historical controls from RTOG-9310, 2-year OS and PFS were significantly improved (P = .006 and .030, respectively). In phase II, the objective response rate was 85.7%. Among patients, 66% (35 of 53) had grade 3 and 4 toxicities before hWBRT, and 45% (24 of 53) of patients experienced grade 3 and 4 toxicities attributable to post-hWBRT chemotherapy. Cognitive function and quality of life improved or stabilized after hWBRT. Conclusion This regimen is safe, with the best 2-year OS and PFS achieved in any Radiation Therapy Oncology Group primary CNS lymphoma trial. Randomized trials that incorporate this regimen are needed to determine its efficacy compared with other strategies.

Treatment of Primary CNS Lymphoma With Methotrexate and Deferred Radiotherapy: A Report of NABTT 96–07

2003 ◽  
Vol 21 (6) ◽  
pp. 1044-1049 ◽  
Author(s):  
Tracy Batchelor ◽  
Kathryn Carson ◽  
Alison O’Neill ◽  
Stuart A. Grossman ◽  
Jane Alavi ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Single Agent ◽  
Primary Cns Lymphoma ◽  
Entire Group ◽  
Cns Lymphoma ◽  
High Dose ◽  
Ocular Involvement ◽  
Karnofsky Performance Score ◽  
End Point ◽  
Grade 3

Purpose: A multicenter, phase II study of single-agent, intravenous methotrexate in newly diagnosed non-AIDS-related primary CNS lymphoma was conducted in the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium. Methods: Methotrexate (8 g/m2) was initially administered every 2 weeks. The primary end point was radiographic CR or PR, as defined by standard radiographic criteria, and secondary end points were survival and drug-related toxicity. Results: Twenty-five patients were enrolled with a mean age of 60 years and median Karnofsky Performance Score of 80. Three of 14 patients who underwent lumbar puncture had malignant cells on CSF cytopathology, and five of 25 patients had ocular involvement. Two patients could not be evaluated for the primary end point because of the absence of measurable disease in one and death before radiologic imaging in another. All patients have completed the treatment program or progressed. Among 23 patients, there were 12 CR (52%), five PR (22%), one (4%) with stable disease, and five progressions (22%) while on therapy. Seven patients died of tumor progression, and two died of other causes. Median progression-free survival was 12.8 months. Median overall survival for the entire group had not been reached at 22.8+ months. The toxicity of this regimen was modest, with no grade 3 or 4 toxicity in 13 of 25 patients, grade 3 toxicity in eight of 25 patients, and grade 4 toxicity in four of 25 patients after 287 cycles of chemotherapy. Conclusion: These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion (74%) comparable to more toxic regimens.

Rituximab, Methotrexate, Procarbazine and Lomustine (R-MPL) for the Treatment of Primary CNS Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-49
Author(s):  
Eyal Lebel ◽  
Neta Goldschmidt ◽  
Tali Siegal ◽  
Alexander Lossos ◽  
Moshe Gatt ◽  
...  
Keyword(s):  
Medical Center ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Response To Treatment ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Rare Type ◽  
End Of Treatment ◽  
Grade 3

Introduction: Primary central nervous lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma that may involve the brain, spinal cord, leptomeninges and vitreous. The median age at diagnosis is in the fifth decade and most patients (pts) present with significant neurologic deficit and a low performance status. The optimal treatment of PCNSL is controversial. High dose methotrexate (HDMTX) is a standard treatment of PCNSL and is more effective when given in combination with other CNS-penetrating medications, which, however, add to the toxicity of the treatment. We aimed to evaluate the effectiveness and the safety of the combination of rituximab, HDMTX, procarbazine and lomustine (R-MPL) in pts with PCNSL. Patients and methods: We retrospectively reviewed the files of PCNSL pts treated in Hadassah Medical Center, Jerusalem, Israel, between the years 2006-2019. The medical records were reviewed for demographic details and initial disease characteristics (age, sex, performance status, laboratory results, cerebrospinal fluid (CSF) content and tumor location), and for therapeutic details including chemotherapy protocol, toxicity, response to treatment and survival. We excluded pts who could not receive HDMTX. The R-MPL is a 42-day cycle protocol, consisting IV Rituximab 375 mg/m2 on days 1, 15 and 28, IV HDMTX 5 g/m2 (3.5 g/m2 for pts &gt; 60 Years (y)) on days 2, 15 and 29, PO procarbazine 100 mg/m2 (60 mg/m2 for pts &gt; 60 y) on days 3-9, PO lomustine 60 mg/m2 (40 mg/m2 for pts &gt; 60 y) on day 2. Six to nine intrathecal (IT) injections of MTX / cytarabine were included for pts with positive CSF cytology, tumor adjacent to ventricles, or per physician's decision. Rituximab was given for no more than 8 doses in total. A total of 3-4 courses of R-MPL were given. Responsive pts could proceed to autologous stem cell transplant (ASCT) with TECAM conditioning or 2 cycles of intermediate dose cytarabine (IDAC, 1.5 g/m2), 2 doses in each cycle. Those who achieved less than CR or had significant toxicity to R-MPL received additional ifosfamide/etoposide or high dose cytarabine or temazolamide or topotecan. Radiation was given only for salvage. Results: Fifty-two pts were included in the study. Median age was 62 years (range 28-94). Three (6%) had leptomeningeal involvement, thirteen (25%) had vitreoretinal involvement, 30 (58%) had involvement of the deep brain. Mean ECOG, IELSG and MSKCC scores were 1.98, 2.53 and 1.94 respectively. The median number of HDMTX doses was 8 (range 3-16). Forty-five (87%) pts completed at least one 42-day cycle of R-MPL. Among this group, 29 (64%) pts received at least 3 IT injections, 12 (27%) underwent ASCT, 10 (22%) received IDAC, and 7 (16%) received other chemotherapies. The median follow-up was 27 months (m) (range 0.4-140m). The overall response rate (ORR) was 79% (41/52), and the complete response (CR) rate was 52% (27/52). The median progression free survival (PFS) was 15.5m and the median overall survival (OS) was 27m. Among the 45 pts who received at least one R-MPL cycle, the ORR was 87% (39/45), the CR rate was 60% (27/45), the median PFS was 84m and the median OS was not reached (figure 1). Known prognostic factors correlated with OS: age (p&lt;0.01), ECOG performance status (p&lt;0.01), CSF protein (p=0.01) and IELSG/MSKCC scores (p=0.05/0.04). Patients who received at least 3 IT injections had a trend to longer PFS (32.4m Vs 19.2m, p=0.09), and a significant OS benefit (48.6m Vs 20.8m, p&lt;0.01). In a multivariable model, the effect of IT injections was independent of age, sex and IELSG score, and attenuated by number of HDMTX doses. ASCT/IDAC did not improve PFS/OS, however numbers were small. Achieving CR at the end of treatment strongly correlated with PFS/OS, but timing of best response (after one 42-day cycle Vs later) did not. Grade 3-4 adverse events included infections (21%) and kidney injury (13%). Two pts died during therapy, both in the 1st cycle due to disease progression. Ten pts (19%) discontinued therapy due to toxicity. No treatment related mortality (TRM) was documented. Conclusions: The R-MPL protocol achieved a favorable ORR/PFS/OS as described, with reasonable grade 3-4 toxicity and no TRM. The advantage of ASCT/IDAC could not be assessed due to small number of pts. IT injections (at least 3) and achievement of CR at the end of treatment correlated with survival. The R-MPL protocol was reported in previous trials only among the elderly, and should further be evaluated in all age groups. Disclosures Goldschmidt: Abbvie Inc: Consultancy, Research Funding.

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