Comparison Of Treatment Results Using High-Dose MTX Plus High-Dose AraC and High-Dose MTX Plus CHOP Regimens For Primary Central Nervous System Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5102-5102
Author(s):  
Hitoji Uchiyama ◽  
Miki Kiyota ◽  
Kazuna Tanba ◽  
Eri Kawata ◽  
Teruaki Akaogi ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Prognostic Score ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Risk Groups ◽  
The Other ◽  
High Dose ◽  
Newly Diagnosed ◽  
Treatment Results ◽  
Free Survival

Abstract Background Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma. High-dose (HD) methotrexate (MTX) plus HD cytarabine (AraC) followed by whole-brain radiation therapy (WBRT) is currently considered the standard therapy for PCNSL. However, at present, the prognosis of patients is not always favorable, because neurotoxicity, particularly dementia, occurs in long-surviving patients at a high rate, and affects their quality of life. In recent years, therapy without WBRT has been attempted in patients, particularly the elderly. In this study, we investigated whether the prognosis of PCNSL patients was improved by the use of different therapeutic regimens. Patients and Methods Japanese patients with newly diagnosed PCNSL who had been admitted to our insutitute between January 2002 and March 2013 were retrospectively analyzed. Their medical records were reviewed regarding the histopathological diagnosis, performance status (PS), prognostic factors used by the International Extranodal Lymphoma Study Group (IELSG), and therapeutic regimens. Data were tabulated, stratified, and analyzed in terms of response rates and overall and progression-free survival. The response to treatment was evaluated by brain MRI. Overall and progression-free survival were estimated using the Kaplan-Meier method. The statistical analysis of observed differences was assessed using the log-rank test. Results Thirty-two patients with newly diagnosed PCNSL were admitted. Their median age at the start of treatment was 71 years (range, 42-86 years), with a male-to-female ratio of 21: 11. All patients were HIV-antibody-negative. Whole-body CT or FDG-PET excluded secondary CNS lymphoma in all patients. All of them underwent biopsy, and 28, 1, 1, and 2 were histopathologically diagnosed with diffuse large B-cell lymphoma, MALT lymphoma, ALK-negative anaplastic large-cell lymphoma, and unclassified type, respectively. In 25 patients, cerebrospinal fluid examination was performed, enabling the calculation of the IELSG prognostic score. Based on the prognostic score, 8, 14, and 3 patients were classified as high-, intermediate- and low-risk groups, respectively. Twenty-two patients received 6 courses of 3-3.5 g/m2 of HD-MTX (adjusted based on creatinine clearance) plus 2 courses of 4-6 g/m2of HD-AraC for 2 days with or without WBRT (30-36 Gy), while 4 underwent HD-MTX plus rituximab (R)-CHOP (6 courses) with or without WBRT. Four and 1 received WBRT and R-CHOP alone, respectively. The median follow-up period was 13 months (range, 1-123 months), and the overall response rate was 81.2% (complete and partial responses in 19 and 7 patients, respectively). To date, 14 patients have died, and 9 patients have survived. In all patients, the overall survival (OS) and progression-free survival (PFS) were 30 and 25 months, respectively. The median OS were 5 and 29 months in the high- and intermediate-risk groups, respectively, and the median OS was not reached in the low-risk group (p=0.03). On the other hand, the median PFS were 5, 20, and 77 months, respectively (p=0.07). No significant difference in the OS or PFS was observed between the HD-MTX plus HD-AraC and HD-MTX plus R-CHOP groups. However, univariate analysis showed that the OS and PFS were significantly improved in both groups treated with regimens including WBRT (p=0.005 and 0.008, respectively). Analysis by age revealed that the overall survival rate was significantly poorer in patients older than 65 years (p=0.03). Stratification based on PS and the use/non-use of rituximab showed no significant differences in the treatment results. Conclusions The treatment results were comparable in the HD-MTX plus HD-AraC and HD-MTX plus R-CHOP groups. On the other hand, the results of regimens with were better than those without WBRT. Thus, HD chemotherapy alone is insufficient for the management of PSCNL, and this study reinforced the importance of WBRT. We consider that HD chemotherapy regimens including HD-MTX and WBRT remain the standard therapy for PCNSL. The results also suggest that R-CHOP can be substituted for HD-AraC, and that it is necessary to reconsider the treatment strategy for PCNSL in the era of rituximab. Disclosures: Taniwaki: celgene: Research Funding.

scholarly journals Efficacy and Safety of Promace-Cytabom Regimen with Sandwiched Radiotherapy Method in the Treatment of Newly Diagnosed, Stage IE to IIE, Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3006-3006
Author(s):  
Young-Woo Jeon ◽  
Sung-Soo Park ◽  
Jae-Ho Yoon ◽  
Sung-Eun Lee ◽  
Byung-Sik Cho ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
The Other ◽  
Combined Chemotherapy ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Nasal Type ◽  
Grade 3 ◽  
Major Adverse Events

Abstract Background: On the basis of the characteristics of extranodal natural killer T (NK/T)-cell lymphoma (ENKTL) which is predisposed to have the multidrug resistance phenotype and radiosensitivity, combined chemotherapy-radiotherapy is one of the effective options in localized early-stage, ENKTL, nasal type. However, frequent severe myelosuppression (grad 3/4 cytopenia), grade 3 radiation-related mucositis, and local/systemic relapse is a major obstacle. So we evaluated the proMACE-cytaBOM (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, and methotrexate) as a slightly less intense regimen with sandwiched radiotherapy (36 Gy). Patients and Methods: From July 2005 to December 2014, Thirty-one patients with newly diagnosed, stage IE to IIE, nasal type ENKTL were analyzed retrospectively. Twenty patients received the chemoradiotherapy sandwiched method: Initially 3 cycles of proMACE-cytaBOM, followed by radiotherapy of 36 Gy, after sandwiched radiotherapy and additional 3 cycles of proMACE-cytaBOM were administered. The other eleven patients were treated with following: Two patients received the frontline autologous hematopoietic stem cell transplantation, five patients were treated with sequential chemoradiotherapy as VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone) followed by radiation of 50 Gy. Four patients received the chemotherapy alone (4 to 6 cycles of proMACE-cytaBOM). Results: In twenty patients with completely proMACE-cytaBOM and sandwiched radiotherapy schedule, median age was 50-year (range 26 to 79), with male-dominant (85%). A median of 6 (range, 4-6) cycles of proMACE-cytaBOM were administered, and sandwiched radiotherapy was received with a median 36 Gy (range 34.5 to 36) (Table1). Interim analysis after 3 courses of proMACE-cytaBOM showed that an overall response rate (ORR) of 82.6%, with complete remission (CR) and partial remission (PR) achieved in 73.9% and 8.7%, respectively. On treatment completion with chemotherapy and sandwiched radiotherapy, the ORR was increased to 90.0%, with CR rate increased to 85%. One patient experienced disease progression, and the other one was within stable disease during therapy. With a median follow-up of 42 months (range 5.5 to 81.4), the 5-year overall survival and progression-free survival were 83.6% (95% CI, 69 to 95 %) and 45.9% (95% CI, 45 to 95%), respectively (figure 1). Grade 3/4 neutropenia developed in 25% (n=5) of patients and grade 3 radiation-related mucositis in 10% (n=2). There was no regimen treatment-related mortality (TRM) (Table 2). Conclusion: The proMACE-cytaBOM regimen with sandwiched radiotherapy (36 Gy) could be a promising and feasible option in the treatment of newly diagnosed localized ENKTL due to its favorable efficacy and tolerable low toxicities including of low radiation-related mucositis and no TRM. Table 1 patient demographic and characteristics Table 1. patient demographic and characteristics Table 2 major adverse events of therapy in twenty patients with localized ENKTL Table 2. major adverse events of therapy in twenty patients with localized ENKTL Figure 1 Overall survival and progression-free survival after combined chemotherapy with sandwiched radiotherpay Figure 1. Overall survival and progression-free survival after combined chemotherapy with sandwiched radiotherpay Disclosures No relevant conflicts of interest to declare.

scholarly journals High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junyao Yu ◽  
Huaping Du ◽  
Xueshi Ye ◽  
Lifei Zhang ◽  
Haowen Xiao
Keyword(s):  
Meta Analysis ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Dose Methotrexate

AbstractWith the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

Rituximab Plus Hypercvad Alternating with High Dose Methotrexate and Cytarabine for Patients with Newly Diagnosed Mantle Cell Lymphoma. A Multicenter Trial from GISL

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3050-3050 ◽  
Author(s):  
Francesco Merli ◽  
Stefano Luminari ◽  
Fiorella Ilariucci ◽  
Caterina Stelitano ◽  
Mario Petrini ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Hematological Toxicity ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Dose Methotrexate ◽  
Mantle Cell

Abstract BACKGROUND. Rituximab plus HyperCVAD alternating with High Dose Methotrexate and Cytarabine (R-HCVAD) has been tested in patients with newly diagnosed Mantle Cell Lymphoma (MCL) with promising results (Romaguera et al. JCO 2005). In 2005 the Gruppo Italiano Studio Linfomi (GISL) started a phase II multicenter study investigating clinical activity and toxicity of R-HCVAD in a similar group of patients. PATIENTS AND METHODS. To be included in the trial patients must have histologically confirmed diagnosis of MCL, be younger than 70 years, have adequate organ function. Chemotherapy consisted of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicine, and dexamethasone(considered one cycle) alternating every 21 days with rituximab plus high dose methotrexate-cytarabine (considered one cycle) for a total of eight cycles per the MD Anderson protocol. Patients with baseline PCR positivity for t(11;14) on bone marrow (BM) had to perform PCR assessment of BM at evaluation of response and during follow-up. Only patients achieving partial response (PR) were to be addressed to HDC followed by ASCT. RESULTS. Thirty-two patients were enrolled. There were 23 males and 9 females; median age was 54 yrs (29 to 66), 80% were in stage IV, 50% and 71% had Gastrointestinal (GI) and BM involvement, respectively; PCR for t(11;14) was positive on BM in 51% of cases. Seven patients did not complete treatment due to toxicity; of these, two patients died (one with septic shock at cycle 1, one with pulmonary aspergillosis at cycle 4), one patient had thrombosis of central line extended to right atrium at cycle 1, one had grade IV skin reaction at cycle 3, one had a severe pneumonia at cycle 1, two had persistent grade IV hematological toxicity after cycle 1 and 5, respectively. All patients had grade III–IV hematological toxicity. Response was assessed in 17 patients with 16 CR and 1 PR. PCR for t(11;14) negativity on BM was achieved in 4/9 patients after cycle 4 and in 8/9 after cycle 8. After a median follow-up of 24 months 1 patient progressed at 6 months and 1 patient relapsed after 26 months of follow-up. Two-year Failure Free Survival (FFS) was 75% (IC95% 53 to 87) and 2 year Disease Free Survival was 93%(IC95% 59–99). CONCLUSIONS. Though longer follow-up is needed R-HCVAD regimen used in our multicenter setting confirmed high efficacy in terms of response (both clinical and molecular) and FFS. However the regimen was associated to a severe toxicity profile that caused treatment discontinuation in several patients and that may limit its use in the clinical setting.

High Remission Rates and Prolonged Progression Free Survival in Newly Diagnosed Patients with Mantle Cell Lymphoma Treated with R-MACLOIVAM-T

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3597-3597 ◽  
Author(s):  
Peter J Hosein ◽  
Daniel Morgensztern ◽  
Francine Coleman ◽  
Gail Walker ◽  
Maricer Escalon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Relapse Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Mantle Cell ◽  
Grade 3

Abstract Background: Mantle cell lymphoma (MCL) is an unfavorable subtype of B-cell non-Hodgkin lymphoma characterized by median progression-free survival (PFS) and median overall survival (OS) of only 1.5 and 3–4 years respectively. Although high-dose therapy and an autotransplant may prolong OS, it does not result in a long-term disease free survival. Therefore, there is a need for novel therapeutic approaches for this entity. Methods: We conducted a single-arm phase II study in subjects with newly-diagnosed MCL to assess efficacy and safety of a novel intensive regimen R-MACLO-IVAM-T, a modification of a protocol designed by Magrath et al (JCO1996;14:925). The study size of 22 patients was based on precision of a two-sided 95% confidence interval for the 18-month progression free survival rate. Eligible subjects had a confirmed diagnosis of MCL using WHO criteria, age 18–75 years, ECOG PS ≤ 2, adequate organ function and no history of HIV or prior cancer. Lymphoma extent at presentation was assessed by standard staging procedures as well as esophagogastroduodenoscopy and colonoscopy. Prior to initiating thalidomide maintenance, subjects were enrolled in the STEPS® program. Cycle 1 consisted of R-MACLO: rituximab 375 mg/m2 IV on day 1, doxorubicin 45 mg/m2 IV on day 1, cyclophosphamide 800 mg/m2 IV on day 1 and 200 mg/m2/day on days 2–5, vincristine 1.5 mg/m2 on days 1 and 8 capped to 2mg, methotrexate 1.2 g/m2 IV on day 10 over 1 hour followed by 5.52 g/m2 IV over 23 hours followed by leucovorin 36 hours later. G-CSF was begun on day 13. When the ANC was >1.5×109/L, cycle 2 with R-IVAM was begun: rituximab 375 mg/m2 IV day 1, cytarabine 2 g/m2 IV every 12 hours on days 1 and 2, etoposide, 60 mg/m2 on days 1–5 and ifosfamide 1.5 g/m2 on days 1–5 with mesna. Fourteen days after ANC recovery from cycle 2, cycles 3 and 4 were given in identical fashion to 1 and 2. Four weeks after ANC recovery from cycle 4, subjects were re-staged and responses were assessed by standard criteria. Subjects achieving CR at the end of therapy received thalidomide 200 mg/day until MCL relapse or intolerable toxicity. Results: Accrual started in 4/2004 and ended in 3/2008 when the planned 22 subjects were enrolled. All subjects were evaluable for toxicity and 21 were evaluable for response. Median age was 56.5 years (range 39–73). All subjects had at least stage 3 disease with bone marrow involvement in 19 and gastrointestinal involvement in 10. Distribution according to IPI: 0–1 factor, 3; 2 factors, 8; 3 factors, 8; and 4 factors, 3. Twenty subjects had diffuse variant and 2 had blastic variant. Nineteen subjects completed all 4 cycles of therapy; treatment was stopped in 2 subjects after 2 and 3 cycles respectively, and one subject died during the first cycle. Of the 21 subjects completing 2 cycles of therapy, 20 achieved CR and one PR. Two subjects relapsed at 9 and 33 months respectively, while 19 remain relapse free after median follow-up of 25 months (range 5–51). With a total follow-up of 545 months, the estimated relapse rate is 4.4 per 100 patients per year. There were two deaths: 1 from sepsis on cycle 1 day 8 and the other in CR at 38 months from non-small cell lung cancer diagnosed 19 months after MCL. Common severe toxicities were grade 3–4 neutropenia, thrombocytopenia and anemia in 33%, 19% and 17% of R-MACLO cycles and in 50%, 88% and 68% of R-IVAM cycles respectively. There were 14 bacteremias in 82 cycles, 12 of which were after R-IVAM therapy. Six episodes of reversible grade 1–2 renal toxicity occurred after methotrexate. The thalidomide maintenance dose was reduced in 6 subjects due to grade 3–4 neutropenia and reduced or stopped in 8 subjects because of grade 3–4 peripheral neuropathy. Patients remain under follow-up for relapse and survival. Conclusions: R-MACLO-IVAM-T results in a high overall response rate of 100% (95% CR and 5% PR) and a low relapse rate. At a median follow-up of 25 months, median PFS and OS were not reached. The 2-year actuarial PFS of 94% compares favorably with previously reported 2-year actuarial PFS of 40% and 67% for CHOP-like regimens without and with upfront bone marrow transplantation (Blood2005;105: 2677). The contribution of thalidomide maintenance to this outcome requires additional study. A multicenter clinical trial is suggested.

First Interim Efficacy and Safety Analysis of an International Phase III Randomized Trial in Newly Diagnosed Systemic Peripheral T-Cell Lymphoma Treated with Chemotherapy with or without Alemtuzumab and Consolidated by High Dose Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 57-57 ◽  
Author(s):  
Francesco d'Amore ◽  
Sirpa Leppä ◽  
Maria Gomes da Silva ◽  
Thomas Relander ◽  
Peter De Nully Brown ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Phase Iii ◽  
High Dose ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
High Dose Therapy ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
Younger Patients ◽  
Grade 3

Abstract Abstract 57 Background The ACT trial (ACT-1, younger patients aged 18–60 yrs and ACT-2, elderly patients aged >60 yrs) is the first international randomized phase III trial in newly diagnosed primary systemic peripheral T-cell lymphoma (PTCL). It tests, in both younger and elderly patients, the efficacy of the addition of alemtuzumab (ALZ) to 6 courses of bi-weekly CHOP followed, only in younger patients (ACT-1), by high-dose therapy with autologous stem cell rescue. A dose reduction amendment tapering the cumulative ALZ dose from 360 mg (30 mg on days 1 and 2 of CHOP courses 1–6) to 120 mg (30 mg on day 1 of CHOP courses 1–4), respectively, was introduced early on due to two cases of systemic fungal infection (Blood 2011,118;4110). To date, the trial has accrued a total of 186 patients (ACT-1 n=98; ACT-2 n=88). Aim Here, we present the results from the first interim efficacy and safety analysis of the ACT-1 trial based on the first 68 randomized patients. Results Of the 68 patients, 63 had a complete set of treatment data. The median follow-up was 15 months (range 0.5–42 months). Thirty-two patients belonged to the experimental arm (exp) and 31 to the standard arm (std). Of the 32 patients treated according to exp, 4 received the higher dose of ALZ and 28 the lower. Treatment arms were well balanced with regard to main prognostic features such as age (std: median 53 yrs, range 21–60 yrs; exp: median 50 yrs, range 22–64 yrs; p=0.705), IPI subgroups (std: low 10%, low-intermediate 51%, intermediate-high 29%, high 10%; exp: low 12%, low-intermediate 44%, intermediate-high 19%, high 25%; p=0.392), advanced clinical stage (std: stage III-IV 94%; exp: 97%; p=0.613), performance status ECOG>1 (std: 23%; exp: 28%; p=0.613), elevated LDH (std: 68%; exp: 69%; p=0.932), presence of B-symptoms (std: 68%; exp: 75%; p=0.524), bulky disease (std: 13%; exp: 13%; p=1.0) and bone marrow involvement (std: 39%; exp: 31%; p=0.535). Histological subtypes were also similarly distributed among both treatment arms (std: PTCL-NOS 55%, AILT 23%, other 22%; exp: PTCL-NOS 56%, AILT 28%, other 16%). No cases of anaplastic large cell PTCL (regardless of ALK-protein status) were included. Neither of the treatment cohorts showed significant treatment delay. The median duration of chemotherapy (calculated for 5 bi-weekly cycles of an expected cumulative duration of 70 days) for non-ALZ vs. ALZ-treated patients was 73 vs. 81 days, respectively. No suspected unexpected serious adverse reactions (SUSARs) were reported. Grade 4 leucopenia was more frequent in ALZ-treated patients (std: 24%, exp: 69%; p=0,001), whereas grade 3–4 anemia and grade 3–4 thrombocytopenia were not significantly different between treatment arms (anemia, std: 19%, exp: 31%; p=0,278; thrombocytopenia, std: 20%, exp: 12%, p=0,682). Non-hematological toxicity unrelated to infectious complications was mild and had a similar frequency in both arms. The number of serious adverse events (SAEs) per patient was 0.86 for patients treated at post-amendment ALZ dose levels, representing a significant reduction compared to the pre-amendment value (3.25), and 0.46 for patients treated in the control arm (p=0.002). The frequency of bacterial and fungal infections (grade ≥3) was similar in both treatment arms. ALZ treated patients had more viral events (9/32; 28% vs. 3/31; 10%), mainly (6 out of 9) consisting of asymptomatic cytomegalovirus reactivations. The overall (non-arm specific) 1-year event-free survival (primary end-point), progression-free survival and overall survival were 55% (95% CI: 42%-67%), 54% (95% CI: 42%-67%) and 78% (95% CI: 67%-88%), respectively. Conclusion The safety profile of the current standard and experimental treatment schedules, as well as the interim outcome results, support a continuation of the trial. A final analysis will be performed in Q2 2015. Disclosures: Jantunen: Genzyme: Has participated in EU Leadership meeting organized by Genzyme as well as Medical Advisory Board meeting organized by Genzyme Other, Honoraria.

Targeting Complete Response with Upfront Bortezomib Followed By Autologous Transplantation and Consolidation Therapy for Untreated Multiple Myeloma (TUBA study)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3463-3463
Author(s):  
Hideki Nakasone ◽  
Kiriko Terasako-Saito ◽  
Teiichi Hirano ◽  
Atsushi Wake ◽  
Seiichi Shimizu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Induction Treatment ◽  
High Dose ◽  
Induction Phase ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
Free Survival

Abstract [Background] Multiple myeloma (MM) is generally considered incurable. Recently, novel drugs, including bortezomib, have demonstrated a survival benefit for newly diagnosed MM patients compared with classical treatments. Complete response (CR) after treatment is known to be associated with superior progression-free survival. Thus, we prospectively evaluated the efficacy and safety of boretezomib + dexamethasone (BD) for patients with newly diagnosed MM, followed by autologous hematopoietic stem cell transplantation (ASCT). We added BD consolidation therapy to aim CR if CR was not achieved after ASCT. [Patients and methods] This clinical study prospectively recruited newly diagnosed MM patients eligible for ASCT between 2010 and 2012. Due to health insurance issues in Japan, two courses of high-dose dexamethasone (HD-DX) had been administrated prior to BD induction treatment until Nov. 2011, while BD was administrated as an initial induction treatment since Dec. 2011. BD induction treatment included 1.3 mg/m2 of bortezomib on days 1, 4, 8, and 11 with 20mg of dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. This BD induction cycle was repeated every 3 weeks for 4 courses. Thereafter, filgrastim-based mobilization and ASCT following high-dose melphalan administration was performed. If patients did not achieve CR after ASCT, BD consolidation therapy (bortezomib: 1.3 mg/m2 on days 1, 8, and 15; dexamethasone 20 mg/day on days 1-2, 8-9, and 15-16) every 4 weeks was added to target CR (Figure 1) (UMIN-CTR: UMIN000002442). [Results] The median observational duration among survivors was 1536 days (range: 464-2023) at this analysis. Of the 47 enrolled MM patients, 46 (male 27; female 19) were eligible for BD induction treatment, while the remaining one achieved CR before BD induction. The median age of the patients was 59 (range: 35-67) years. Of the 44 patients whose karyotype analyses were available, normal karyotype was observed in 35. Abnormal karyotype included complex type in 4, diploid in 1, and other abnormalities in 4. FISH revealed deletion of p53 in 5 of 39 patients whose information was available; deletion of 13-chromosome in 16 of 42, IgH-MAF fusion in 1 of 40; IgH-FGFR3 fusion in 5 of 41; IgH-BCL1 fusion in 9 of 39. Of the 46 MM patients, 19 received HD-DX prior to BD induction, and 34 received ASCT after BD induction treatment (Figure 1). During the BD induction phase, 3 patients experienced disease progression, and BD treatment was discontinued in 9 patients because of their consent withdrawal (n=2) and adverse events (n=7) including interstitial pneumonia in 2, persistent neuropathy in 1, CMV enterocolitis in 1, heart failure in 1, diabetes mellitus in 1, and liver dysfunction in 1. After BD induction phase (n=46), their response was >= CR in 4 (8%), very good partial response (VGPR) in 10 (22%), partial response (PR) in 18 (39%), stable disease (SD) in 2 (4%), and progression or withdrawal in 12 (26%). After ASCT, their response was >=CR in 9 (20%), VGPR in 11 (24%), PR in 12 (26%), SD in 1 (2%), and additional progression or withdrawal in 1 (2%). Of the 24 patients who received ASCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses (range: 1- 8). BD consolidation was discontinued in 4 patients due to persistent neuropathy or cytopenia. Finally, maximum response after ASCT with or without BD consolidation was >= CR in 19 (41%), VGPR in 7 (15%), PR in 6 (13%), < SD in 2 (2%, Figure 2). Through BD consolidation, CR was achieved in 8 of 11 patients with post-ASCT VGPR and 2 of 12 patients with post-ASCT PR. In total, 4-year progression-free survival (PFS) and overall survival (OS) was 43% (95%CI: 28-57%) and 80 % (95%CI: 64-90%), respectively. Focusing on CR patients after ASCT and those who actually received BD consolidation, PFS adjusted for karyotype and age were not different between CR patients after ASCT and after BD consolidation, while patients with VGPR or less after consolidation had significantly lower PFS (Figure 3). [Conclusion] BD induction and ASCT provided CR rate of 27% among ASCT patients, although BD induction may expectedly cause adverse events including persistent neuropathy and viral infections. Patients who achieved CR after ASCT showed good PFS, and targeting CR through BD consolidation might improve CR rate. It is worthwhile to prospectively compare the efficacy of BD consolidation only for patients who failed to achieve CR or universal consolidation strategy. Disclosures Kanda: Otsuka Pharmaceutical: Honoraria, Research Funding.

Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 686-692 ◽  
Author(s):  
Joerg Hasford ◽  
Michele Baccarani ◽  
Verena Hoffmann ◽  
Joelle Guilhot ◽  
Susanne Saussele ◽  
...  
Keyword(s):  
High Risk ◽  
Kinase Inhibitors ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
Risk Groups ◽  
High Risk Group ◽  
Prognostic Scores ◽  
Imatinib Treatment ◽  
Free Survival ◽  
Eutos Score

AbstractThe outcome of chronic myeloid leukemia (CML) has been profoundly changed by the introduction of tyrosine kinase inhibitors into therapy, but the prognosis of patients with CML is still evaluated using prognostic scores developed in the chemotherapy and interferon era. The present work describes a new prognostic score that is superior to the Sokal and Euro scores both in its prognostic ability and in its simplicity. The predictive power of the score was developed and tested on a group of patients selected from a registry of 2060 patients enrolled in studies of first-line treatment with imatinib-based regimes. The EUTOS score using the percentage of basophils and spleen size best discriminated between high-risk and low-risk groups of patients, with a positive predictive value of not reaching a CCgR of 34%. Five-year progression-free survival was significantly better in the low- than in the high-risk group (90% vs 82%, P = .006). These results were confirmed in the validation sample. The score can be used to identify CML patients with significantly lower probabilities of responding to therapy and survival, thus alerting physicians to those patients who require closer observation and early intervention.

scholarly journals Autologous Stem Cell Transplantation with Thiotepa, Busulfan, and Cyclophosphamide Conditioning in Patients with Primary Central Nervous System Lymphoma: A Remarkable Outcome Form Single-Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3462-3462 ◽  
Author(s):  
Seyoung Seo ◽  
Jung Yong Hong ◽  
Dok Hyun Yoon ◽  
Jeong Hoon Kim ◽  
Young Hyun Cho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Prognostic Score ◽  
Central Nervous System Lymphoma ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Baseline Characteristics

Abstract Introduction High dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has been adopted as an effective treatment in patients with relapsed or refractory primary central nervous system lymphoma (PCNSL) and also has been proposed as a consolidative treatment option for newly diagnosed PCNSL. HDC-ASCT may overcome chemoresistance mediated by blood-brain barrier by affording higher drug concentrations in the central nervous system. We investigated the feasibility of thiotepa, busulfan, and cyclophosphamide (TBC) conditioning followed by ASCT in patients with PCNSL. Method Between December 2012 and July 2015, a total of 27 patients with PCNSL underwent TBC conditioning followed by ASCT. Those with a complete or partial response after induction chemotherapy or salvage chemotherapy proceeded with TBC conditioning followed by ASCT. TBC conditioning consists of thiotepa 250 mg/m2 on days -9 to day -7, busulfan 3.2 mg/kg on days -6 to day -4 and cyclophosphamide 60 mg/kg on days -3 to day -2. The event free survival (EFS) was defined from the date of transplant to the date of relapse, progression or any cause of death, while overall survival (OS) was calculated from the date of transplant to death. Result Baseline characteristics were summarized in table 1. Twenty patients received TBC conditioning followed by ASCT as a consolidative therapy after high-dose methotrexate-based induction chemotherapy and the other 7 patients received TBC conditioning followed by ASCT after salvage chemotherapy due to relapsed or refractory disease. The median time to neutrophil recovery (absolute neutrophil count >500/uL) and platelet recovery (>20000 x103/uL) were 8 (range, 7-9) and 8 (range, 4-15) days, respectively. All 27 patients experienced febrile neutropenia and 33.3% of patients (9/27) and 7.4% of patients (2/27) had documented bacterial and viral infection, respectively. Commonly observed nonhematologic grade 3 or 4 toxicities were mucositis (63%), diarrhea (59.3%) and nausea (25.9%). The 100-day transplant-related mortality rate was 0%. With median follow-up duration of 27.8 months (range 6.7-42.6), median EFS and OS were not reached. The 2-year EFS and OS estimates were 76.8% (95% CI: 68.4-85.2) and 88.9% (95% CI: 82.9-94.9), respectively (Figure 1). Conclusion ASCT with TBC conditioning appears to be feasible in patients with PCNSL. Although survival outcomes are encouraging, longer follow-up is required. Further studies are warranted to investigate the role of ASCT with TBC conditioning in both clinical settings of consolidative treatment of newly diagnosed PCNSL and salvage treatment of relapsed or refractory PCNSL. Table 1 Baseline characteristics (n=27) *Conventional cytology; flow cytometry not performed $The cutoff for normal CSF protein concentration was 45 mg/dL in patients ¡Â 60 years old and 60 mg/dL in patients more than 60 years old. *MSK RPA, Memorial Sloan-Kettering prognostic score determined by recursive partitioning $Periventricular, basal ganglia, brainstem and cerebellar lesion Table 1. Baseline characteristics (n=27). / *Conventional cytology; flow cytometry not performed. / $The cutoff for normal CSF protein concentration was 45 mg/dL in patients ¡Â 60 years old. / and 60 mg/dL in patients more than 60 years old. / *MSK RPA, Memorial Sloan-Kettering prognostic score determined by recursive partitioning. / $Periventricular, basal ganglia, brainstem and cerebellar lesion Figure 1 Event-free survival and overall survival. Figure 1. Event-free survival and overall survival. Disclosures No relevant conflicts of interest to declare.

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