Consolidation reduced dose whole brain radiotherapy (rdWBRT) following methotrexate, rituximab, procarbazine, vincristine, cytarabine (R-MPV-A) for newly diagnosed primary CNS lymphoma (PCNSL): Final results and long-term outcome.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2006-2006 ◽  
Author(s):  
Richard Charles Curry ◽  
Denise Correa ◽  
Jeffrey J. Raizer ◽  
Sean Aaron Grimm ◽  
Rose Lai ◽  
...  
Keyword(s):  
Verbal Memory ◽  
Primary Cns Lymphoma ◽  
Cognitive Outcomes ◽  
Cognitive Testing ◽  
Cns Lymphoma ◽  
Newly Diagnosed ◽  
Long Term Outcome ◽  
Early Results

2006 Background: After promising early results in the pilot phase (N= 30) reported by Shah 2007, we report on final results of a multicenter phase II study (N=52) in newly diagnosed PCNSL combining R-MPV-A and rdWBRT, expanded to address long-term disease control and cognitive outcomes in pts who actually received rdWBRT. Methods: Pts received 5 cycles of R-MPV (MTX dose: 3.5g/m2). Those with partial response (PR) received additional 2 cycles. Pts with a complete response (CR) after 5-7 cycles received rdWBRT (23.4 Gy), otherwise standard WBRT was offered (45 Gy). Consolidation cytarabine was given to all pts. Primary end-point was 2-y progression-free survival (PFS) in pts receiving rdWBRT (n=30 pts in CR required). Exploratory end-points included comprehensive neuropsychological testing, white matter changes (WMC) analysis (Fazekas scale) and apparent diffusion coefficient (ADC) on MRI. Results: Accrual was completed (N=52; 22 women); median (med) age= 60 (30-79); med KPS= 70 (50-100). In total, 31 (59%) pts were assessable for the primary endpoint (achieved a CR after induction and received rdWBRT). The 2-y PFS for this group was 78% (95% ci: 64%- 92%); med PFS= 7.7 y; the med OS was not reached (med follow-up= 6y); 3y-OS= 88% (ci 70-95); 5y-OS= 81% (ci 62-91). Cognitive testing showed improvement in executive function (P < 0.01) and verbal memory (P < 0.05) following induction chemotherapy; follow-up scores remained stable across the various domains. Minimal WMC developed in long term survivors: 36% of pts showed no change in Fazekas’ scores, 64% of pts developed scores 1 or 2 and no pt showed scores 3-6. The intent-to-treat (n=52) med PFS was 3.3y; med OS= 6.6 y. Differences in ADC values did not predict response (p=0.15), PFS (p=0.41) or OS (p=0.48). Conclusions: Consolidation rdWBRT is a highly effective and safe treatment for newly diagnosed PCNSL. Long term follow-up showed robust PFS and OS, comparable or superior to full dose WBRT, with excellent cognitive outcomes and no significant WMC over time. An RTOG randomized trial has been initiated comparing R-MPV-A with vs without rdWBRT.

scholarly journals Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome

2013 ◽  
Vol 31 (31) ◽  
pp. 3971-3979 ◽  
Author(s):  
Patrick G. Morris ◽  
Denise D. Correa ◽  
Joachim Yahalom ◽  
Jeffrey J. Raizer ◽  
David Schiff ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
Karnofsky Performance Score ◽  
Whole Brain ◽  
Long Term Outcome ◽  
Reduced Dose ◽  
Brain Radiotherapy

Purpose A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma. Patients and Methods Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor. Results Fifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R-MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was 7.7 years. Median overall survival (OS) was not reached (median follow-up for survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3 years, and median OS was 6.6 years. Cognitive assessment showed improvement in executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and follow-up scores remained relatively stable across the various domains (n = 12). All examined MRIs (n = 28) displayed a Fazekas score of ≤ 3, and no patient developed scores of 4 to 5; differences in ADC values did not predict response (P = .15), PFS (P = .27), or OS (P = .33). Conclusion R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity.

Long-term follow-up of vanishing tumors in the brain: How should a lesion mimicking primary CNS lymphoma be managed?

2012 ◽  
Vol 114 (9) ◽  
pp. 1217-1221 ◽  
Author(s):  
Yoshiko Okita ◽  
Yoshitaka Narita ◽  
Yasuji Miyakita ◽  
Makoto Ohno ◽  
Shintaro Fukushima ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Long Term Follow Up ◽  
The Brain

Necessity of Intraventricular Chemotherapy with the Modified Bonn Protocol in Primary CNS Lymphoma (PCNSL) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2452-2452
Author(s):  
Ingo G.H. Schmidt-Wolf ◽  
Hendrik Pels ◽  
Annika Juergens ◽  
Axel Glasmacher ◽  
Holger Schulz ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Free Survival ◽  
Intraventricular Chemotherapy ◽  
High Infection ◽  
Intraventricular Treatment

Abstract Background: Treatment of primary CNS lymphoma (PCNSL) with a combined systemic and intraventricular chemotherapy (Bonn protocol) has achieved an overall response rate (ORR) of 84% and long term complete remissions in a substantial fraction of patients younger than 60 years. Purpose: Due to a high infection rate of the Ommaya reservoir the question was addressed if intraventricular treatment is dispensable in this polychemotherapy protocol. Patients and Methods: Fifty patients with histologically confirmed PCNSL were enrolled onto a phase II-study evaluating chemotherapy without radiotherapy and without intraventricular treatment. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was administered. Results: In an ongoing trial thirty-five of 50 patients (18 pat. < 60 years, 17 pat. over 60 years) are yet assessable for response after a median follow up of nine months (range: 1 to 26 months). In 18 patients < 60 years, the ORR was 78%. However, median time to treatment failure (TTF) was eight months, and median progression free survival (PFS) only 7 months according to frequent early relapses. Conclusions: Early relapses are frequent in younger patients treated with the modified Bonn protocol without intraventricular treatment despite a high ORR. These preliminary results support the assumption that intraventricular treatment is essential to achieve sustained remissions after successful treatment of PCNSL.

Rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) followed by consolidation high-dose chemotherapy (HDC) and autologous stem-cell transplant (ASCT) for newly diagnosed primary CNS lymphoma (PCNSL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2008-2008 ◽  
Author(s):  
Antonio Marcilio Padula Omuro ◽  
Denise Correa ◽  
Craig Moskowitz ◽  
Matthew J. Matasar ◽  
Lisa Marie DeAngelis ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Primary Endpoint ◽  
Primary Cns Lymphoma ◽  
Unknown Etiology ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Induction Regimen

2008 Background: In our previous study in newly diagnosed PCNSL, induction chemotherapy with MTX and cytarabine followed by consolidation HDC (carmustine, etoposide, cytarabine, melphalan [BEAM]) with ASCT without radiotherapy resulted in only 50% of pts transplanted, reflecting low efficacy of induction chemotherapy, and short intent-to-treat (ITT) median PFS (=6m). In this phase II trial, we sought to optimize this strategy by utilizing a more effective induction regimen (R-MPV) and a more aggressive HDC regimen (Soussain et al). Methods: Pts received 5-7 cycles of R-MPV (MTX: 3.5g/m2) and if a partial or complete response was achieved, HDC with thiothepa, cyclophosphamide and busulfan was given, followed by ASCT and no radiotherapy. The primary endpoint was ITT 1 year event-free survival (promising: 75%, non-promising: 50%; 90% power, significance=0.05). Follow-up included comprehensive neuropsychological evaluation. Results: Accrual has been completed (N=32 pts, median age 57 [range 23-67], median KPS=80). Following R-MPV, 17 pts achieved a CR, 13 pts a PR and two pts progressed. A total of 25 (78%) pts were transplanted; the reasons for not receiving transplant were progressive disease (N=2), poor performance status/ physician’s decision (N= 2), mobilization failure (N=1) and consent withdrawn (N= 2). One pt who withdrew consent relapsed and received HDCASCT for salvage. Two (8%) pts died from early complications of ASCT (Stevens-Johnson: one, sepsis: one) and one pt experienced a fatal late colitis of unknown etiology. In the ITT population, the median EFS and OS have not been reached after a median follow-up of 22 months. The 1 year EFS was 78% (95%CI 58-90) and the 2y OS was 76% (95% CI 54-89). No pt has developed delayed neurotoxicity. Conclusions: R-MPV induction regimen resulted in improved response rates, allowing 78% of pts to receive HDC-ASCT. Although more toxic, this regimen resulted in excellent disease control and survival in the ITT population, far exceeding the efficacy of our previous transplant study. The primary endpoint was met, warranting further investigation.

scholarly journals Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8096-8096 ◽  
Author(s):  
Geetika Srivastava ◽  
Vishal Rana ◽  
Martha Lacy ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Entire Cohort ◽  
Dexamethasone Therapy

8096 Background: The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma. While the short-term outcomes with respect to response and toxicity is well-known, long-term outcome with this combination as initial therapy is not well described. Methods: We studied 286 consecutive patients with newly diagnosed MM seen at our institution, who received initial therapy with Len-Dex, and who had complete follow up records. Data regarding the clinical course was obtained from medical records. Results: The median (range) age at diagnosis was 63 (28-92) yrs; 166 (58% were ≤ 65 yrs and175 (61%) were male. The median estimated follow-up was 3.9 yrs (95% CI, 3.4, 4.2) and 203 (71%) pts were alive at the time of last follow up. The median estimated duration on Len-Dex was 5.3 mos (95% CI, 4.6, 6.4). The best overall response (≥PR) was 72%, including 26% with VGPR or better and 14 (5%) not being evaluable for a response. At last follow up, 41 (14%) patients were continuing on therapy. There were 93 pts (32%) who stayed on therapy for 12 months or more. Among these patients, the ORR was 86%, including 45% with VGPR or better. The median overall survival (OS) for the entire cohort from diagnosis was 7.4 yrs (95% CI; 5.8, NR) and the estimated 5-yr survival was 67%. There were 16 (5.5%) pts who died within a year of diagnosis. The median time to first disease progression, irrespective of transplant status, was 30.2 mos (95% CI, 25, 42). Overall, 143 (50%) of the patients have gone to stem cell transplant. Censoring those patients who proceeded to SCT prior to relapse at the time of BMT, the median TTP was 25.5 mos (95% CI, 22, 29). The median OS was 7.4 yrs for those ≤65 yrs, compared with 6.2 yrs for the older patients (P=0.01). The 5-yr OS estimate for patients in ISS stage 1, 2 and 3 were 82, 65, and 44 months respectively. Conclusions: The current study provides long-term estimates of responses and survival in a series of patients treated initially with lenalidomide and dexamethasone. The median survival of nearly 8 years reflects the efficacy of the novel agents both at diagnosis and at relapse and confirms the survival improvements seen in MM in the last decade.

Beneficial Effects of Cytogenetic and Molecular Response on Long-Term Outcome in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib (IM): Update from the IRIS Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 166-166 ◽  
Author(s):  
Bengt Simonsson ◽  
Keyword(s):  
Blast Crisis ◽  
Chronic Phase ◽  
Risk Groups ◽  
Low Risk ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Long Term Outcome ◽  
Increased Risk

Abstract Background: IM was proven to be superior to IFN+Ara-C for newly diagnosed pts with CML-CP (O’Brien et al, NEJM 2003). At 42-months of follow-up, 75% of the 553 pts randomized to IM remain on treatment. Of the 553 pts randomized to IFN+Ara-C only 4% are still on IFN+Ara-C. This update analysis is focused on IM pts. Methods: Evaluation included complete hematologic response (CHR), major/complete cytogenetic response (MCyR/CCyR) - defined as 0-35% Ph+ and 0% Ph+ metaphases respectively, major molecular response (MMR) - defined as ≥3 log reduction of bcr-abl transcripts from the standardized baseline, time to progression - defined as loss of CHR/MCyR or evolution to accelerated phase/blast crisis (AP/BC) or death due to any cause, time to AP/BC - defined as evolution to AP/BC or death due to CML, and overall survival. Results: With an average duration of 38 months of IM treatment, the best observed rates of CHR, MCyR and CCyR are 96%, 88% and 81%, respectively. Although the majority of MCyRs were achieved within the first 3 to 9 months, some pts achieved a MCyR and some even a CCyR after more than one year of treatment (Figure 1). The estimated MMR rate at 12 months is 40%. Figure 1 - Observed CHR, MCyR and CCyR during treatment with IM Figure 1 -. Observed CHR, MCyR and CCyR during treatment with IM The estimated progression-free rate at 42 months is 84%; additionally 94% are estimated free of progression to AP/BC (97% of the pts with CCyR and 73% of the pts without CCyR during study, p<0.001). The risk of relapse remains low with no apparent increased risk over time. The yearly hazard for progression to AP/BC is about 2% in each of the 4 years. The overall estimated survival at 42 months is 91% (considering all deaths). The estimated survival was lowest in pts with high risk Sokal score (84%) as compared to 91% in the intermediate risk pts and 94% in the low risk pts (p<0.001). Similarly, the best observed CCyR in the high, intermediate, and low risk groups were 69%, 80% and 88% respectively (p=0.002). In the subset of pts with CCyR the estimated survival at 42 months was 92%, 93% and 97% in the high to low risk groups (p=0.30), indicating that once pts achieve a CCyR, their survival is not significantly different between the Sokal risk groups. Of the 509 pts who were still on treatment at 12 months and had achieved a MCyR by then (n=436), the rate without progression to AP/BC at 42 months was 97% whereas it was only 83% for the 73 pts who did not achieve a MCyR at 12 months (p<0.001). The estimated survival rates at 42 months were 95% and 83% in these two response groups, respectively (p<0.001). Furthermore, for pts who had achieved a MMR at 12 months, the probability of remaining free from progression to AP/BC was 100% at 42 months compared to 95% for pts in CCyR but not in MMR, and 91% for pts not in CCyR at 12 months (p=0.0013). Conclusions: The follow-up confirms the beneficial effect of cytogenetic and molecular responses on long-term outcomes with IM. These results will be further updated using data cut-off of 31-July 2005 to reflect additional 12-months of data (i.e., 54-month follow-up).

scholarly journals Twenty-year follow-up of a pilot/phase II trial on the Bonn protocol for primary CNS lymphoma

Neurology ◽  
2020 ◽  
Vol 95 (23) ◽  
pp. e3138-e3144
Author(s):  
Sabine Seidel ◽  
Hendrik Pels ◽  
Sabine Schlömer ◽  
Annika Kowoll ◽  
Klaus Fliessbach ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
Karnofsky Performance Score ◽  
Class Iii ◽  
Entire Cohort ◽  
Brain Radiotherapy ◽  
Long Term Follow Up

ObjectiveTo determine whether a fraction of patients with primary CNS lymphoma (PCNSL) had been cured by systemic and intraventricular methotrexate- and cytarabine-based chemotherapy (Bonn protocol) after a very long-term follow-up of nearly 20 years.MethodsSixty-five patients (median age 62 years, range 27–75; median Karnofsky performance score 70, range 20–90) had been treated with systemic and intraventricular polychemotherapy without whole brain radiotherapy from September 1995 until December 2001. All patients still alive in 2019 were contacted and interviewed on their current life situation.ResultsMedian follow-up for surviving patients was 19.6 years (17.5–23.3 years). Out of 65 patients, 11 (17%) were still alive. Six of those never experienced any relapse. For the whole study population, median overall survival (OS) was 4.4 years (95% confidence interval [CI] 2.9–5.9); for patients ≤60 years, 11.0 years (95% CI 4.8–17.0). The 10-year OS rate for the entire cohort was 29% and the estimated 20-year OS rate was 19%. Four late relapses were observed after 9.8, 10.3, 13.3, and 21.0 years.ConclusionAt a median follow-up of 19.6 years, 17% of patients were alive and free of tumor; however, even after response for decades, an inherent risk of relapse, either systemic or cerebral, characterizes the biology of PCNSL.Classification of evidenceThis work provides Class III evidence that PCNSL treatment with methotrexate-based polychemotherapy including intraventricular therapy is associated with long-term disease control in some patients.

Evidence of time-dependent prognostic factors predicting early death but not long-term outcome in primary CNS lymphoma: a study of 91 patients

2012 ◽  
Vol 31 (2) ◽  
pp. 57-64 ◽  
Author(s):  
Hervé Ghesquières ◽  
Youenn Drouet ◽  
Marie Pierre Sunyach ◽  
Catherine Sebban ◽  
Catherine Chassagne-Clement ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Primary Cns Lymphoma ◽  
Early Death ◽  
Time Dependent ◽  
Cns Lymphoma ◽  
Term Outcome ◽  
Long Term Outcome
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