High Rate of Durable Remissions After Treatment of Newly Diagnosed Aggressive Mantle-Cell Lymphoma With Rituximab Plus Hyper-CVAD Alternating With Rituximab Plus High-Dose Methotrexate and Cytarabine

2005 ◽  
Vol 23 (28) ◽  
pp. 7013-7023 ◽  
Author(s):  
Jorge E. Romaguera ◽  
Luis Fayad ◽  
Maria A. Rodriguez ◽  
Kristine R. Broglio ◽  
Frederick B. Hagemeister ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Mantle Cell ◽  
Overall Survival Rates

Purpose To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL). Patients and Methods This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles. Results Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients ≤ 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred. Conclusion Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.

Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.

1998 ◽  
Vol 16 (12) ◽  
pp. 3803-3809 ◽  
Author(s):  
I F Khouri ◽  
J Romaguera ◽  
H Kantarjian ◽  
J L Palmer ◽  
W C Pugh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Mantle Cell ◽  
Previously Treated

PURPOSE Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.

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.

scholarly journals Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas – a single centre experience

2016 ◽  
Vol 51 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Lucka Boltezar ◽  
Karlo Pintaric ◽  
Jože Pretnar ◽  
Maja Pohar Perme ◽  
Barbara Jezersek Novakovic
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Treatment ◽  
Mantle Cell

Abstract Background Advanced follicular lymphoma (FL) and mantle cell lymphoma (MCL) are incurable diseases with conventional treatment. The high dose treatment (HDT) with autologous stem cell transplantation (ASCT), however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS) and overall survival (OS) in patients with FL and MCL treated with ASCT. Patients and methods Seventeen patients with FL and 29 patients with MCL were included, 15 of them were transplanted to consolidate the response to second line treatment and 24 to consolidate their first remission, respectively. All were conditioned with total body irradiation (TBI) and high dose cyclophosphamide between 2006 and 2014 and all were transplanted with peripheral blood stem cells. Results The estimated 5-year OS for FL was 87.8% (95% confidence interval [CI] 59.5%–96.8%) and for MCL 79.3% (95% CI 56.1%–91.1%), respectively. The estimated 5-year EFS for FL was 76.0% (95% CI 48.0%–90.3%) and for MCL 69.8% (95% CI 45.5%–84.8%), respectively. There were no secondary hematological malignancies observed in either group. Conclusions Based on above results, the ASCT with TBI is a good treatment option in terms of long-term survival for patients with follicular and mantle cell lymphoma demonstrating a relatively low rate of late toxicities and secondary malignancies.

Rituximab maintenance improves progression-free and overall survival rates after combined immuno-chemotherapy (R-FCM) in patients with relapsed follicular and mantle cell lymphoma: Final results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7502-7502 ◽  
Author(s):  
M. Dreyling ◽  
R. Forstpointner ◽  
M. Gramatzki ◽  
H. Böck ◽  
M. Hänel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Remission Induction ◽  
Low Grade ◽  
Free Survival ◽  
Mantle Cell ◽  
The Impact

7502 Background: Rituximab (R) prolongs the progression-free survival (PFS) in patients with follicular lymphoma (FL) when given either simultaneously with or as maintenance after chemotherapy only. Methods: In the current study the impact of R maintenance after remission induction with an R-containing combined immuno-chemotherapy (R-FCM) was evaluated. Patients with advanced stage relapsed or refractory FL and mantle cell lymphoma (MCL) were eligible. The study design comprized 4 courses of chemotherapy with Fludarabine (25 mg/m2/d days 1–3), Cyclophosphamide (200 mg/m2/d days 1–3) and Mitoxantrone (8 mg/m2/d day 1) (FCM) ± Rituximab (375 mg/m2/d day 0). Patients entering a complete (CR) or partial remission (PR) underwent a second randomization for R maintenance (4 weekly doses (375 mg/m2/d) at three and nine months after end of induction) or observation only. Randomization was stratified for histology, prior therapies (up to 2 lines vs. >2), induction (±R), and response (CR vs. PR). After improved outcome of the R-FCM arm had been observed in the initial 147 randomized patients, all subsequent patients received a combined immuno-chemotherapy induction. Results: 176 of 195 randomized cases are evaluable, 138 of whom had received an R-containing induction. In these patients (as well as the total group) the median PFS after end of induction has not been reached in the R-maintenance arm in contrast to 17 months in patients with no further treatment (p = 0.001). This improvement was seen both in FL (n = 81; p = 0,035) and MCL (n = 47; p = 0,049). More importantly, overall survival rate was also improved after R maintenance with borderline significance (3 y rate 82% vs. 55%; p = 0,056). No major sided effects of R maintenance have been observed and the rate of serious infections was similar in both study arms (p = 0.72). Conclusions: The final analysis of this study confirms that R maintenance after combined immuno-chemotherapy (R-FCM) is highly effective and improves the progression-free survival—with a strong trend towards improved overall survival—of patients with relapsed FL and MCL. [Table: see text]

Prognostic value of the absolute lymphocyte to monocyte (ALC/AMC) ratio on overall survival among patients with mantle cell lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19030-e19030 ◽  
Author(s):  
Andre Goy ◽  
Tatyana Feldman ◽  
Lori Ann Leslie ◽  
Alan P. Skarbnik ◽  
Tommy Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Cancer Center ◽  
Mantle Cell

e19030 Background: The peripheral blood absolute lymphocyte-to-monocyte ratio (ALC/AMC) is prognostic of overall survival (OS) in Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma, and several solid tumors. Lymphocyte and monocytes have been suggested to be surrogate biomarkers of immune homeostasis and tumor microenvironment, respectively. We sought to determine if the post-induction therapy ALC/AMC is prognostic in mantle cell lymphoma. Methods: A retrospective review was conducted of 96 consecutive mantle cell lymphoma patients (pts) with available data treated at the John Theurer Cancer Center (n=77) and 4 Regional Cancer Care Associate practices (n=19) by 24 physicians between Aug 2005 and Dec 2015 (90% cases after 2009). Cases were identified via the COTA database which extracts and organizes relevant data from the electronic health records. Peripheral blood counts (to calculate the ALC/AMC) were determined approximately 30 days following completion of initial therapy or immediately prior to stem cell mobilization in those pts undergoing first line transplant. All analyses were performed using the R statistical language. Results: 67 pts had ALC/AMC less than 2 and 29 pts had ALC/AMC greater than or equal to 2. The cohorts (<2 vs >2) had similar median ages (64 vs 68; p=0.18), ethnicities (p=0.38), stage distributions (including 87% vs 79% stage IV disease; p=0.51), elevated beta-2-microglobulin (p=1), elevated LDH (p=1) and MIPI scores (including 19% vs 41% high risk; p=0.13). ALC/AMC was <2 in 10 of 13 (77%) transplanted pts and 57 of 83 (69%) non-transplanted pts (p=0.57). With a median follow-up of 43 months, the median OS has not been reached in either cohort; the 5-year survival rates were higher among pts with ALC/AMC greater than or equal to 2 (90% vs 68%; log-rank p<0.05). Similar ALC/AMC 5-year survival trends were noted when sub-setting to the 25 pts with high risk MIPI scores (72% vs 45%; p=0.07). Conclusions: An elevated ALC/AMC >2, following induction therapy, is associated with improved overall survival in MCL. Novel maintenance programs, including targeting the microenvironment or immune response, might be appropriate among pts with low ratios.

scholarly journals Treatment outcomes and survival in patients with primary central nervous system lymphomas treated between 1995 and 2010 – a single centre report

2012 ◽  
Vol 46 (4) ◽  
pp. 346-353 ◽  
Author(s):  
Barbara Jezersek Novakovic
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Median Overall Survival ◽  
Systemic Treatment ◽  
Cell Lymphoma ◽  
Combined Therapy ◽  
Primary Treatment ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Background. Primary central nervous system lymphomas (PCNSL) are rare variants of extranodal non-Hodgkin′s lymphomas that are nowadays primarily treated with high-dose methotrexate or methotrexate-based chemotherapy with or without radiation therapy. The optimal treatment of PCNSL is still unknown and there are differences in clinical practice. Patients and methods. With a retrospective research we evaluated our series of patients with PCNSL in regards to the patient′s characteristics, treatment results, disease specific survival and overall survival. Fifty nine patients who attended the Institute of Oncology Ljubljana between 1995 and 2010 were treated according to the protocol that was valid at the time of the patient′s admission. Between 1995 and 1999, the systemic treatment was classical CHOP (cyclophosphamide, doxorubicin, vincristine, steroids) chemotherapy, and later on high-dose methotrexate either alone or in combination with other agents. From 1999 onwards, radiation therapy was applied according to the patient′s age and response to chemotherapy, prior to that all patients treated with CHOP were also irradiated. Patients ineligible for the systemic treatment were treated with sole radiation therapy. Results. There was a strong female predominance in our series and the median age at diagnosis was 59.8 years. Patients had predominantly aggressive B cell lymphomas (69.5%), one patient had marginal cell lymphoma and two patients T cell lymphoma. In total, 20.3% of patients were treated just with chemotherapy, 33.9% with combined therapy and 42.4% with sole radiation therapy. The overall response rate to the primary treatment in patients treated with sole chemotherapy was 33.3%, in patients treated with combined therapy 65% and in patients treated only with radiation therapy 56%, respectively. In terms of response duration, significantly better results were achieved with combined therapy or radiation therapy alone compared to sole chemotherapy (p<0.0006). The median overall survival of the whole cohort was 11 months and the overall survival was significantly affected by the patient′s age. The longest overall survival was observed in patients treated with combined therapy (median survival of 39 months). Patients treated just with radiation therapy had a median overall survival of 9 months and those treated with sole chemotherapy of 4.5 months, respectively. Conclusions. The treatment outcomes in ordinary clinical practice are definitely inferior to the ones reported in clinical trials. The now standard treatment with high-dose methotrexate with or without radiation therapy is sometimes too aggressive and, therefore, a careful selection on the basis of patient′s age, performance status and concomitant diseases of those eligible for such treatment is mandatory. According to our results from a retrospective study, radiation therapy should not be excluded from the primary treatment.

scholarly journals The Intensity of the Induction Regimen Does Not Affect Post-Transplant Survival Among Patients with Newly Diagnosed Mantle Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2915-2915
Author(s):  
Melhem Solh ◽  
Asad Bashey ◽  
Lawrence E Morris ◽  
H. Kent Holland ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
High Dose ◽  
Post Transplant ◽  
Mantle Cell ◽  
Induction Regimen ◽  
High Dose Cytarabine

Abstract The routine use of autologous stem cell transplantation (ASCT) in first remission have significantly improved outcomes for patients with mantle cell lymphoma (MCL) (Hermann et al, jco 2009). The choice of the most appropriate induction regimen prior to transplant remains a controversial topic. Adding high dose cytarabine to RCHOP among young patients (&lt;65 years) results in superior PFS, higher toxicity but no improvement in overall survival when compared to RCHOP alone (Hermine O et al, Lancet 2016). The use of bendamustine/Rituxan (BR) compared to RCHOP in 2 randomized studies showed lower toxicity, higher PFS but similar overall survival. In this study, we investigated the effect of induction regimen intensity and the use of high dose cytarabine on post autologous stem cell transplant outcomes among MCL patients treated at our center. 59 patients who received ASCT for MCL between 2010 and 2020 were included in this analysis. Data were retrieved from our database where it was entered prospectively. Median age at diagnosis was 60 (45,76) years, stage IV (85%), B symptoms (32%), MIPI score (low 17%, intermediate 47%, high 28%) and ECOG performance 0-1 (81%). Induction regimen included BR (n=14), RCHOP (n=11), R-Hyper CVAD (n=14), RBAC(n=2) and RCHOP/RDHAP (n=18). 85% of patients were in CR and 15% in PR at time of transplant. All patients underwent chemo mobilization with a median time from diagnosis to transplant of 251 (119,1372) days. 30 patients (51%) received post-transplant rituximab maintenance. Patients were compared into 2 groups based on the use of high dose cytarabine in their induction regimen (table 1). Patients who received high dose cytarabine were younger and had a shorter time from diagnosis to transplant that patients who were treated without cytarabine. Survival endpoints for cytarabine based and no cytarabine based induction at 5 years post-transplant were as follows OS (82% vs 69%), DFS (65% vs 50%), Non-relapse mortality (4% vs 9%) and relapse (31% vs 41%) respectively ( figure 1). A multivariable cox analysis for OS, DFS, NRM and relapse showed that cytarabine had no effect on any of the endpoints. For OS, B symptoms and worse ECOG performance at Diagnosis (&gt;=2) were associated with worse OS. For relapse, higher MIPI score and no use of Rituxan maintenance resulted in higher relapse. In conclusion, our data shows that among MCL patients receiving ASCT, the use of more intensive cytarabine based induction does not clearly improve long-term outcomes It is possible that use of ASCT compensates for the use of a less intense induction regimen. Disease (MIPI), Patient (ECOG)characteristics and use of post-transplant maintenance are factors that contribute to post transplant outcomes. Figure 1 Figure 1. Disclosures Solh: Jazz Pharmaceuticals: Consultancy; Partner Therapeutics: Research Funding; BMS: Consultancy; ADCT Therapeutics: Consultancy, Research Funding.

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