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

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.

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

BioMed Research International ◽

10.1155/2015/927105 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 8

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.

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

Blood ◽

10.1182/blood.v112.11.3597.3597 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3597-3597 ◽

Cited By ~ 2

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.

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Rituximab Added to Aggressive Chemotherapy Improves the Outcome of Patients with Follicular Lymphoma, Grade 3 and Results In Survival Comparable to Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v116.21.2810.2810 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2810-2810

Author(s):

Philip J. Bierman ◽

Julie M. Vose ◽

R. Gregory Bociek ◽

Fausto R. Loberiza ◽

Martin Bast ◽

...

Keyword(s):

Overall Survival ◽

Follicular Lymphoma ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Bulky Disease ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Extranodal Disease ◽

Grade 3

Abstract Abstract 2810 The survival of patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma is improved when rituximab is combined with chemotherapy. However, little is known about the outcome of patients with follicular lymphoma, grade 3 (FL-3), since these patients are generally excluded from DLBCL trials and often from trials evaluating treatment of follicular lymphoma. We therefore performed a retrospective study to evaluate the results of rituximab-based therapy for FL-3. An analysis of the Nebraska Lymphoma Study Group database allowed us to identify patients with FL-3 who were treated with aggressive combination chemotherapy regimens with and without the addition of rituximab. The progression-free survival (PFS) and overall survival of these patients were compared to patients with DLBCL who were treated with similar aggressive chemotherapy regimens combined with rituximab. Patients who were not treated with anthracycline-containing or mitoxantrone-containing regimens were excluded from analyses. We identified 60 FL-3 patients who were treated with aggressive chemotherapy regimens, combined with rituximab, between Feb. 1999 and Jan. 2009. The median age was 56 years (range 37–87 years). There were 27 males and 33 females. The performance status was 0–1 in 80%, the LDH was elevated in 15%, 68% had stage III-IV disease, and 13% had at least 2 sites of extranodal disease. Fifteen patients (25%) had bulky disease (≥5 cm) at diagnosis. The results of treatment for these patients were compared to 144 FL-3 patients treated with aggressive chemotherapy regimens without rituximab between June 1983 and Jan. 1999, and to 341 patients with DLBCL who were treated with aggressive chemotherapy regimens combined with rituximab between Sept. 1996 and Jan. 2009. The treatment outcomes for these three groups of patients are displayed in the table. 5-yr Estimate (95% CI) 8-yr Estimate (95% CI) Log-Rank p-value Progression-Free Survival 0.04 FL-3 with rituximab 65% (50–77) 45% (23–65) FL-3 without rituximab 42% (34–50) 33% (26–41) DLBCL with rituximab 53% (47–58) 47% (40–54) Overall Survival 0.06 FL-3 with rituximab 85% (72–92) 71% (54–82) FL-3 without rituximab 68% (59–74) 54% (46–62) DLBCL with rituximab 64% (58–69) 56% (48–63) A multivariate analysis (accounting for older patients, and more patients with elevated LDH, extranodal disease, and bulky disease in the DLBCL group) revealed that patients with FL-3 who were not treated with rituximab had a significantly higher risk of disease progression or death (RR 1.75; p=0.02). There were no significant differences in PFS when comparing patients with FL-3 and those with DLBCL who were treated with aggressive chemotherapy regimens and rituximab. Follicular lymphoma, grade 3 patients treated without rituximab had inferior overall survival, when compared to patients treated with rituximab (RR 1.58), although this difference was not significant (p=0.16). The multivariate analysis also revealed no significant differences in survival when patients with FL-3 who received rituximab were compared to similarly treated patients with DLBCL (p=0.50). In conclusion, this analysis demonstrates that the outcome of treatment for patients with FL-3 who are treated with aggressive chemotherapy regimens is improved when rituximab is added to therapy. In the “rituximab era” the outcome of patients with FL-3 is comparable to DLBCL. Disclosures: Vose: Millennium Pharmaceuticals, Inc.: Research Funding.

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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 ◽

10.1182/blood.v122.21.5102.5102 ◽

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.

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Histological Impact on Follicular Lymphoma Grade 3 Treated With Frontline RCHOP Regimen

10.21203/rs.3.rs-151484/v1 ◽

2021 ◽

Author(s):

Feifei Chen ◽

Aziguli Maihemaiti ◽

Zheng Wei ◽

Luya Cheng ◽

Weiguang Wang ◽

...

Keyword(s):

Overall Survival ◽

Follicular Lymphoma ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Baseline Characteristics ◽

Grade 3 ◽

Large B Cell

Abstract Background Histologically, follicular lymphoma (FL) grade 3 is subdivided into grade 3A and 3B. However, there are limited studies on outcomes of FL grade 3A and 3B treated with frontline of RCHOP treatment. Methods We retrospectively analyzed 61 patients of FL grade 3 treated with frontline RCHOP regimen between January 2009 and December 2019. We divided them into FL grade 3A (n = 42) and aggressive FL (n = 19). Aggressive FL included grade 3A with an additional 3B component (n = 2), grade 3B (n = 8), and grade 3 with areas of diffuse large B cell lymphoma (n = 9). Results The baseline characteristics were similar between FL grade 3A and aggressive FL. The 3-year overall survival (OS) was 97.1% in FL grade 3A and 81.9% in aggressive FL (P = 0.041). The 3-year progression free survival (PFS) was not significantly different between two groups, with 69.1% and 71.1%, respectively (P = 0.546). However, patients of aggressive FL reached a plateau in the PFS curve after 2 years. Conclusions Compared with patients of aggressive FL, FL grade 3A patients presented an uncurable feature but associated with a better OS with frontline RCHOP treatment.

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Rituximab and Bendamustine (BR) Compared with Rituximab, Bendamustine, and Cytarabine (R-BAC) in Previously Untreated Elderly Patients with Mantle Cell Lymphoma

Cancers ◽

10.3390/cancers13236089 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6089

Author(s):

Giulia Bega ◽

Jacopo Olivieri ◽

Marcello Riva ◽

Greta Scapinello ◽

Rossella Paolini ◽

...

Keyword(s):

Propensity Score ◽

Elderly Patients ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Progression Free Survival ◽

Newly Diagnosed ◽

Free Survival ◽

Mantle Cell ◽

Grade 3

Background: Rituximab plus bendamustine (BR), and rituximab, bendamustine, and cytarabine (R-BAC) are well-known induction therapies in elderly patients with mantle cell lymphoma (MCL), according to clinical guidelines. However, a direct comparison between the two regimens has never been performed. Methods: In this multicentre retrospective study, we compared the outcome of patients with newly diagnosed MCL, treated with BR or R-BAC. Primary endpoint was 2-year progression-free survival (PFS). Inclusion bias was assessed using a propensity score stratified by gender, age, MCL morphology, and MIPI score. Results: After adjusting by propensity score, we identified 156 patients (53 BR, 103 R-BAC) with median age of 72 (53–90). Median follow-up was 46 months (range 12–133). R-BAC was administered in a 2-day schedule or with attenuated dose in 51% of patients. Patients treated with R-BAC achieved CR in 91% of cases, as compared with 60% for BR (p < 0.0001). The 2-year PFS was 87 ± 3% and 64 ± 7% for R-BAC and BR, respectively (p = 0.001). In terms of toxicity, R-BAC was associated with significantly more pronounced grade 3–4 thrombocytopenia than BR (50% vs. 17%). Conclusions: This study indicates that R-BAC, even when administered with judiciously attenuated doses, is associated with significantly prolonged 2-year PFS than BR in elderly patients with previously untreated MCL.

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A Novel and Significant Predictor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: The Prognostic Nutritional Index (PNI)

Blood ◽

10.1182/blood.v124.21.1650.1650 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1650-1650

Author(s):

Qingqing Cai ◽

Kailin Chen ◽

Huilan Rao ◽

Wenqi Jiang ◽

Huiqiang Huang ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Natural Killer ◽

Cell Lymphoma ◽

Risk Group ◽

Progression Free Survival ◽

Intermediate Risk ◽

Survival Curves ◽

Free Survival ◽

Nasal Type

Abstract Background: Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis. The prognostic nutritional index (PNI) is reported to be associated with survival in several types of tumors. The prognostic value of PNI in lymphoma remains unclear. The aim of the present study is to evaluate the prognostic significance of PNI in patients with ENKTL. Methods: 157 patients with newly diagnosed ENKTL were retrospectively evaluated between August 2000 and October 2011 at the Sun Yat-sen University Cancer Center. Patients in whom the combined albumin (g /l) +5x total lymphocyte count x 109/l ≥45 were allocated a PNI score of 0. Patients in whom this total was < 45 were allocated a score of 1. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. The significance of differences between survival curves was tested using the log-rank test. Significant variables in the univariate analysis were considered variables for the multivariate survival analysis, which was performed using Cox regression mode. Results: Four-nine patients (31.2%) had an abnormal PNI (PNI=1). The characteristics of both groups are given in Table 1. After a median follow-up duration of 31.0 months, an estimated 5-year OS and PFS rate in 157 patients was 58.4% and 39.4%, respectively. Patients with pretreatment PNI score=1 had lower complete remission rates (P= 0.018) and worse OS (5-year OS: 71.7% vs 21.8.0%,P<0.001) and PFS (P<0.001) compared with PNI score=0 patients. The survival curves according to PNI are shown in Fig. 1. Using the International Prognostic Index (IPI) and peripheral T-cell lymphoma (PIT) scoring systems, more than 70% of all cases were in the low-risk category (with no or one adverse factor), but these two prognostic models failed to differentiate between patients with different outcomes in the low-risk group. PNI could differentiate low-risk patients using IPI and PIT scoring (all P< 0.05). The Korean Prognostic Index (KPI) model balanced distribution of patients into different risk groups better than the IPI and PIT models. However, the KPI model also failed to significantly differentiate between patients with different outcomes in low and low intermediate risk group (P=0.859). PNI also helped to differentiate between patients with different prognosis in low and low intermediate risk group (P=0.000).However, the KPI prognostic model failed to show significant prognostic value among patients with PNI=0 (P=0.646) or among the patients with PNI=1 (P=0.115). The survival curves according to KPI and PNI are shown in Fig. 2. Conclusions: PNI is an independent predictor of survival in ENKTL and is superior to IPI, PIT and KPI. Table 1. Baseline Characteristics of Patients by PNI Level Characteristics PNI score =0 PNI score =1 P 108 49 Age (median [range], yr) 42(9-77) 45(12-76) 0.031 <60 96(88.9) 37(75.5) >60 12(11.1) 12(24.5) Gender 0.444 Female 33(30.6) 18(36.7) Male 75(69.4) 31(63.3) ECOG PS <0.001 0-1 107(99.1) 40(81.6) 2-3 1(0.9) 9(18.4) B symptoms (yes) 45(41.7) 36(73.5) <0.001 LDH >245 U/L 19(17.6) 29(59.2) <0.001 Mass ≥5 cm 12(11.1) 6(12.2) 0.836 Extranodal sites ≥2 30(27.8) 27(55.1) 0.001 Regional LN involvement 60(55.6) 40(81.6) 0.002 Bone marrow involvement 0(0.0) 3(6.1) 0.009 Primary sites 0.006 Nasal/nasopharynx area 93(86.1) 33(67.3) Extra-nasal/nasopharynx 15(13.9) 16(32.7) Ann Arbor stage 0.001 I/II 93(86.1) 31(63.3) III/IV 15(13.9) 18(36.7) IPI score <0.001 0-1 91 (84.3) 24(49.0%) 2-5 17(15.7) 25(51.0%) PIT score <0.001 0-1 106(98.1) 36(73.5) 2-4 2(1.9) 13(26.5) KPI score <0.001 0-1 69(63.9) 9(18.4) 2-4 39(36.1) 40(81.6) Fig. 1 Overall survival (A) and progression free survival (B) based on the PNI for patients with extranodal natural killer/T¨Ccell lymphoma, nasal type. Fig. 1. Overall survival (A) and progression free survival (B) based on the PNI for patients with extranodal natural killer/T¨Ccell lymphoma, nasal type. Fig. 2 KPI model differentiate between patients with different outcomes in low and low intermediate risk group (A) and high and high intermediate risk group (B). PNI differentiate between patients with KPI=0-1 (C) and KPI=2-4(D). KPI model differentiate between patients with PNI=0(E) and PNI=1 (F). Fig. 2. KPI model differentiate between patients with different outcomes in low and low intermediate risk group (A) and high and high intermediate risk group (B). PNI differentiate between patients with KPI=0-1 (C) and KPI=2-4(D). KPI model differentiate between patients with PNI=0(E) and PNI=1 (F). Disclosures No relevant conflicts of interest to declare.

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Prospective Study to Evaluate the Efficacy and Safety of Gemcitabine Combined with GMCSF and Rituximab in Heavily Pre-Treated Relapsed / Refractory B-Lymphoproliferative Disorders

Blood ◽

10.1182/blood.v118.21.1616.1616 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1616-1616

Author(s):

Shinoj Pattali ◽

Stephanie A. Gregory ◽

Melissa Leigh Larson ◽

Jamile M. Shammo ◽

Elena Bogdanova ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Response Rate ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Salvage Regimen ◽

Free Survival ◽

Refractory Lymphoma ◽

Grade 3

Abstract Abstract 1616 Background: Aggressive non-Hodgkin lymphomas (NHLs) are commonly treated with anthracycline-containing combination chemotherapy regimens. Although a proportion of patients can be cured, 40 –50% of patients relapse or are refractory to frontline therapy. High dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is the current standard of care of relapsed aggressive lymphomas in eligible patients. Many patients cannot proceed to HDT as a result of reasons like advanced age, significant co morbidities and resistance to salvage chemotherapy. Moreover, the optimal salvage regimen is not known. Hence there is need to develop novel regimens that are likely to benefit these patients. Gemcitabine and rituximab are active agents in relapsed or refractory lymphoma and have demonstrated synergistic effects. GMCSF has been shown to potentiate the efficacy of Rituximab. In this study we evaluated the clinical activity, toxicity and tolerability of a salvage regimen that incorporated sequential combination of gemcitabine, rituximab and GMCSF (Sargramostim, Leukine). Methods: This trial was designed as a prospective, open and uncontrolled phase II study. 13 patients with relapsed or refractory B cell lymphoma were enrolled from Nov 2001 to Mar 2006 at Rush University Medical Center, Chicago, IL. All patients were scheduled to receive up to 6 cycles of Gemcitabine 800mg/m2 IV infusion over 120 minutes on days 1 and 8, GMCSF 250mcg/m2 subcutaneously once daily on day 9 through 15 (7doses) and Rituximab 375mg/m2 IV infusion on day 16. Cycles were repeated every 21 days to a total of 6 cycles. Responses were evaluated by CT scans and bone marrow exam (if involved) after the third course and at the end of the study. Primary endpoint was response rate. Secondary endpoints were toxicity evaluation, progression free survival (PFS) and overall survival (OS). Patients were followed for toxicity, response, PFS and OS. Results: Of the 13 patients in the study, 9 patients completed 6 cycles of therapy and were evaluable for response. The median age was 43 years (range 24 –75 years) with 6 males (66.6%) and 3 females (33.3%). 92% of patients had very advanced disease with stage III or IV disease (Stage IV-61.5% and stage III-30.8%), and 30.8% were poor risk (IPI 3–5). Major histological subtypes were diffuse large B-cell lymphoma (33.3%), Hodgkin lymphoma (33.3%) and follicular lymphoma (11.1%). Eight patients (88%) demonstrated extra nodal disease at one or more sites at presentation indicating a more aggressive lymphoma. Most of the patients were heavily pretreated with multiple combination chemotherapy or chemo immunotherapy with a median of 3 prior chemotherapy regimens (range 2–6). The majority of patients were complete responders after first line induction therapy. In the intent to treat analysis of responses, the overall response rate was 55.5% with 4 complete responses (44.5%) and 1 partial response (11.1%). Disease progression occurred in 4 patients (44%). Progression free survival ranged from 2 to 71 with a median of 6 months. Overall survival measured from 2 to 102 months with a median of 10 months. At last follow-up 22% of (2 of 9) were alive. Toxicity profile of this regimen was similar to other salvage therapies used in this patient population with an increased incidence of grade 3/4 anemia (15.3%) and thrombocytopenia (7.6%).No grade 3 and 4 non-hematologic toxicities were observed. Conclusions: Based on the result of our study, we conclude that gemcitabine combined with GMCSF and rituximab is an effective, feasible and tolerable regimen in heavily pre-treated aggressive relapsed lymphomas. Long-term remissions are possible in patients with heavily pre-treated relapsed/refractory lymphoma with complete remissions lasting for 78–102 months even in patients who relapsed after autologous peripheral blood stem cell transplantation. Disclosures: Shammo: Celgene Corporation: Honoraria, Research Funding, Speakers Bureau.

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Lenalidomide Maintenance with or without Prednisone in Newly Diagnosed Myeloma Patients: A Pooled Analysis

Cancers ◽

10.3390/cancers11111735 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1735 ◽

Cited By ~ 1

Author(s):

Bonello ◽

Pulini ◽

Ballanti ◽

Gentile ◽

Spada ◽

...

Keyword(s):

Overall Survival ◽

Progression Free Survival ◽

Pooled Analysis ◽

Phase Iii ◽

Newly Diagnosed ◽

Two Phase ◽

Free Survival ◽

Phase Iii Trials ◽

Grade 3 ◽

The Impact

: We conducted a pooled analysis of two phase III trials, RV-MM-EMN-441 and EMN01, to compare maintenance with lenalidomide-prednisone vs. lenalidomide in newly diagnosed transplant-eligible and -ineligible myeloma patients. Primary endpoints were progression-free survival, progression-free survival 2 and overall survival with both regimens. A secondary aim was to evaluate the impact of duration of maintenance on overall survival and on outcome after relapse. A total of 625 patients (lenalidomide-prednisone arm, n = 315; lenalidomide arm, n = 310) were analyzed. The median follow-up was 58 months. Median progression-free survival (25 vs. 19 months; p = 0.08), progression-free survival 2 (56 vs. 49 months; p = 0.9) and overall survival (73 months vs. NR; p = 0.08) were not significantly different between the two arms. Toxicity profiles of lenalidomide-prednisone and lenalidomide were similar, with the exception of neutropenia that was higher in the lenalidomide arm (grade ≥ 3: 9% vs. 19%, p < 0.001), without an increase in the rate of infections. Overall survival (median NR vs. 49 months, p < 0.001), progression-free survival from relapse (median 35 vs. 24 months, p = 0.004) and overall survival from relapse (median not reached vs. 41 months, p = 0.002) were significantly longer in patients continuing maintenance for ≥2 years. We showed that the addition of prednisone at 25 or 50 mg every other day (eod) to lenalidomide maintenance did not induce any significant advantage.

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RT-DeVIC Therapy Is Effective for Localized NK/T Cell Lymphoma Patiens

Blood ◽

10.1182/blood.v124.21.1702.1702 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1702-1702 ◽

Cited By ~ 2

Author(s):

Kyoko Ueda ◽

Noriko Nishimura ◽

Yuko Mishima ◽

Hideaki Nitta ◽

Yoshiharu Kusano ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

T Cell ◽

Local Control ◽

Cell Lymphoma ◽

Progression Free Survival ◽

T Cell Lymphoma ◽

Free Survival ◽

Nk T Cell ◽

Grade 3

Abstract BACKGROUNDS: Extranodal natural killer (NK) /T cell lymphoma, nasal type is much common in East Asia than in Western countries. CHOP therapy is not effective for NK/T cell lymphoma because of the drug resistance induced by P glycoprotein. Yamaguchi et al reported the effectiveness of concurrent radiotherapy and DeVIC (RT-DeVIC) therapy for localized nasal NK/T cell lymphoma. Nowadays, RT-DeVIC therapy is recognized as a standard treatment. So far, we have limited information about this treatment because NK/T cell lymphoma is rare phenotype. PATIENTS AND METHODS: We reviewed retrospectively the patients with localized NK/T cell lymphoma treated with RT-DeVIC therapy. Radiation therapy was administered for a total dose of 50 Gy. Concurrently, chemotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) was performed up to 3 cycles. The primary objectives of this analysis were to evaluate the response rates and progression free survival (PFS) and overall survival (OS). RESULTS: A total of 20 patients who diagnosed as nasal NK/T cell lymphoma between April 2007 and October 2012 were analyzed. Sixteen patients were stage 1E and 4 were Stage 2E. As the NK/T cell lymphoma prognostic index, 6 patients were group 1, 10 were group 2, 3 were group 3, and 1 was group 4. Seventeen patients completed 3 cycles of DeVIC therapy and 19 patients completed planned radiation therapy. Overall response rate (ORR) was 75% and CR rate was 70% in the entire patients. Local control was 90%. Half of the patients who reached CR showed long time survival without disease progression. On the other hand, 7 of 14 patients relapsed after CR, and all 5 patients experienced systemic failure. The sites of relapse were paranasal sinuses (n=2), skin (n=3), brain (n=1), testis (n=1). Among them, one patient reached 2nd CR. However, 5 patients were not eligible for salvage chemotherapy, because lymphoma progressed rapidly and their general condition became worse. Six patients did not reach CR after RT-DeVIC therapy. Five of them experienced systemic relapse and median survival of them was only 8 months. The median follow up time was 17.6 months (range 2 – 77.9 months). Median overall survival was not reached and median progression free survival was 14.6 months. Risk factors predicted of OS or PFS were not clear. All entire patients experienced grade 3 or 4 neutropenia. Mucositis was common non-hematological toxicity and it was the major cause of grade 3 or 4 appetite loss. Only one patient discontinued RT-DeVIC due to grade 3 mucositis, grade 3 dermatitis and septic shock. CONCLUSION: We reviewed treatment outcomes of 20 cases of RT-DeVIC therapy. In this analysis, the majority of relapsed or refractory cases showed systemic disease and the prognosis of these patients were poor. However, RT-DeVIC therapy showed excellent local control and response rates which were similar to the prior study. The effectiveness of RT-DeVIC therapy for patients with NK/T cell lymphoma was reconfirmed. Disclosures No relevant conflicts of interest to declare.

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