Fludarabine, Aracytine and Rituximab Based Chemotherapy In Patients with Refractory and Relapsed Mantle Cell Non-Hodgkin Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4892-4892
Author(s):  
Tommasina Perrone ◽  
Francesco Gaudio ◽  
Annamaria Giordano ◽  
Paola Curci ◽  
Alessandro Spina ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Single Agent ◽  
High Dose ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell

Abstract Abstract 4892 Introduction Mantle cell lymphoma (MCL) is a distinct B cell non Hodgkin lymphoma characterized by CD 5 expression, t (11; 14)(q13; q32) translocation and over-expression of Cyclin D1, and frequently has an aggressive clinical course. There is no standard of care for the treatment of MCL. Current treatment approaches are non curative and pts median survival is 4–6 years. Various studies have reported promising results for a high dose Cytarabine-containing regimen in the treatment of MCL. Fludarabine has also been recognized as effective treatment in pts with MCL, either as a single agent or in combination with other drugs. The addition of Rituximab improves the response to the treatment. The aim of this study is to assess the efficacy and toxicity of a combination of Fludarabine, Aracytine and Rituximab treatment in refractory and relapsed MCL. Methods We retrospectively evaluated 20 pts with refractory or relapsed MCL treated in our institution between February 2007 and February 2010. Median age was 59 yrs (54-77 yrs), 14 pts (70%) were males, 18 pts (90 %) had stage IV, 16 pts (80%) had bone marrow involvement, 16 (80%) presented comorbidities. Eight pts (40%) were in first relapse, 12 (60%) in second relapse. Twelve pts (60%) had a “Mantle Cell Lymphoma International Prognostic Index” (MIPI) score ≥ 7. Therapy included: fludarabine 25 mg/m2/daily intravenously for 3 days, aracytine 500 mg/m2/daily for 3 days and Rituximab 375 mg/m2/daily for 1 day, Dexamethasone 8 mg daily for 3 days, every 28 days for 4 cycles. Results Eight pts (40%) achieved complete response (CR) and 4 pts (20%) a Partial Remission (PR) with an overall response rate (ORR) of 60%. Eight pts (40%) progressed and one of them died of active disease. After a median follow up of 17 months (range 8–36), OS is 70% and PFS is 55%. Toxicity was mainly hematological with grade >=3 neutropenia in 40 (50%) of the 80 cycles performed, grade >=2 anemia in 30 (37%) and grade 4 thrombocytopenia in 24 (30%). In 16 (20%) cycles pts required red blood cells transfusions, in 12 (15%) platelet transfusions. One episode of Herpes Zoster infection was observed. Conclusions This study suggests that the combination of Fludarabine, Aracytine and Rituximab appears to be an effective regimen with a promising response rate and manageable toxicity, for pretreated pts often affected by comorbidities and with poor prognosis. Further studies are needed to assess the efficacy of this combination therapy and to further test the role of this approach in MCL. Disclosures: No relevant conflicts of interest to declare.

Outcomes of Early Relapse Following Non-Myeloablative Allogeneic Transplant for Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1204-1204
Author(s):  
Ron Ram ◽  
Ted Gooley ◽  
David G. Maloney ◽  
Oliver W. Press ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Aggressive Lymphoma ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Early Relapse ◽  
Mantle Cell

Abstract Abstract 1204 Poster Board I-226 Non-myeloablative allogeneic transplantation (NMAT) has provided the potential benefit of allogeneic hematopoietic stem cell transplantation (allo-SCT) to a broader cohort of lymphoma patients via lowered non-relapse mortality (NRM). NMAT also provides a post-transplant platform of a chemotherapy-naïve graft for both myelosuppressive and immune-mediated anti-tumor therapies, though the lack of high-dose conditioning may also heighten the risk for early relapse. Herein, we describe the survival as well as factors associated with outcomes for lymphoma patients experiencing relapse within 200 days of NMAT. Between December, 1997 and April, 2009, 267 lymphoma/CLL patients underwent NMAT at our center, of which 70 (35%) relapsed within 200 days from transplant. Histologies were categorized as aggressive (n= 36) including diffuse large-B-cell (n=22), blastic mantle cell lymphoma (n=10) and T-lymphoblastic lymphoma (n=4), and indolent (n=21) with chronic lymphocytic leukemia (n=15), follicular lymphoma (n=3) and classic mantle cell lymphoma (n=3). We also evaluated patients with Hodgkin Lymphoma (n=13). Conditioning regimens included 2 Gy total body irradiation (TBI), fludarabine 30 mg/m2 daily x 3 days + 2 Gy TBI, and Y-90-Ibritumomab-tiuxetan+ fludarabine 30 mg/m2 daily x 3 days + 2 Gy TBI in 13, 41, and 16 patients, respectively. Grafts were from HLA-matched related (n=34) or unrelated (n=31), HLA-mismatched unrelated (n=3) and HLA-haploidentical related (n=2) donors. Interventions to treat relapse included chemotherapy and/or radiation therapy in 43 (61%) patients and no therapy or withdrawal of immunosuppression in the remaining 27 (39%). Donor lymphocyte infusion (DLI) was attempted in 9 patients. Overall survival (OS) from time of relapse at 3 and 5 years among all 70 patients was 28% (95% CI 16-41%) and 19% (95% CI 9-32), respectively. Aggressive histology was associated with increased mortality relative to indolent histology (HR for death=2.57 [1.28-5.14, p=0.008]), while Hodgkin Lymphoma had similar outcome to the indolent group (HR=1.04 [0.42-2.53, p=.94]). The 3-year OS among patients with aggressive and indolent histologies was 14% (95% CI 3-33%), and 43% (95% CI 21-64%), respectively (Figure). Later relapse was associated with improved survival (p=.01) with patients relapsing between 31 and 100 days and those relapsing between 101 and 200 days having a reduced hazard of mortality relative to those relapsing less within 30 days (HR=0.36 [0.17-0.75, p=.006]; HR=0.30 [0.13-0.69, p=.005], respectively). When both histology and time to relapse were included in one model, these associations were somewhat reduced but the qualitative conclusions remained. In particular, patients with aggressive disease had a 2.16-fold (1.10-4.23, p=.03) increase in mortality compared to patients with Hodgkin or indolent lymphoma; the group that relapsed from 31 to 100 days was 0.41 (0.19-0.88, p=.02) times as likely to die compared to the group that relapsed within 30 days and the group that relapsed 101-200 days was 0.43 (0.17-1.04, p=.06) times as likely to die compared to the early-relapse group. Patients with chemoresistant disease pre-transplant were 1.46 times more likely to die than those with responding disease, but this difference was not statistically significant (95% CI, 0.82-2.62, p=.20). Fifty-nine patients relapsed with measurable disease and had a higher risk of mortality compared to 11 patients with only blood or marrow evidence of relapse, but the difference in mortality was not statistically significant (HR=1.53 [0.71-3.29, p=.28]). Pre-relapse graft-versus-host disease, bone marrow involvement, remission status at transplant, number of prior therapies, comorbidity score, and disease bulk were not statistically significantly associated with survival. These data indicate that despite early relapse of lymphoma after NMAT, some patients can experience prolonged survival with the best outcomes in patients with indolent histology and later relapse, though further improvement in disease control for patients with aggressive lymphoma and very early relapse is needed. Disclosures: No relevant conflicts of interest to declare.

Lenalidomide, Bendamustine, and Rituximab As First-Line Therapy for Patients > 65 Years with Mantle Cell Lymphoma: Results From the Phase I Portion of the Nordic Lymphoma Group MCL4 (LENA-BERIT) Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2700-2700 ◽  
Author(s):  
Mats Jerkeman ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Riikka Räty ◽  
Kirsten Grønbæk ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Phase I ◽  
Mantle Cell Lymphoma ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
Mantle Cell

Abstract Abstract 2700 Background: Mantle cell lymphoma is a disease of the elderly, with a median age of 70 years. Younger patients may be treated with potentially curative treatment including high dose chemotherapy. For elderly patients, however, no standard therapy has been defined. In a randomized comparison between R-CHOP and R-bendamustine (R-B) by the German StiL Group, R-B was associated with less toxicity and improved outcomes, making R-B a preferable first-line treatment option. Lenalidomide (LEN) is another active agent in MCL, with a response rate of 53% as a single agent in relapsed/refractory MCL. In the current trial, we investigate if the addition of lenalidomide to R-B may enhance efficacy, with manageable toxicity, for the older population of MCL patients. Methods: In phase I, the MTD of LEN was to be determined, starting with 5 mg/day increasing up to 25 mg/day in a sequential dose escalation using a 3+3 design. LEN, bendamustine and rituximab are given in 6 cycles/28 days. LEN D1-21, B 90 mg/m2 D1-2 and R 375 mg/m2 D1. The maintenance phase consists of LEN 25 mg/day, D1-21, for 7 cycles. Eligibility criteria are age > 65 years or ≤ 65 years, unable to tolerate high dose chemotherapy, with stage II-IV untreated mantle cell lymphoma. Results: The trial was commenced in October 2009.The phase I portion initially recruited 12 pts according to the original protocol design in 3 cohorts with LEN dose from 5–15 mg d 1–21. Median age was 72.5 years, range 66–85. MIPI high risk n=8, intermediate risk n=4. Response after 6 cycles: CR/CRu n=9/10, PR n=1/10 (ORR 100%). Molecular remission in BM: 5/9 pts. Toxicity was more profound than expected, mostly during cycle 1 (SAE n=9, AE Grade III/IV n=14). Notable was a high incidence of cutaneous and allergic AE. No patients could receive more than 10 cycles, median 6.5. A dose limiting toxicity (DLT) was noted at the dose of 15 mg. This led to a modification of the phase I protocol: Cohort A: No LEN in cycle 1, cycles 2–6: 10 mg LEN days 1–14. During maintenance, cycles 7–8: LEN 10 mg days 1–21, cycles 9–13: LEN 15 mg days 1–21. Cohort B: Same as Cohort A, but reducing B to 70 mg/m2 in cycles 2–6. Cohort C: as Cohort B, but reducing LEN to 5 mg days 1–14 cycles 2–6. In Cohort A, 2 of 6 patients experienced a DLT. Evaluation of Cohort B (6 pts) is ongoing. Conclusions: The addition of LEN to the R-B regimen leads to increased toxicity in elderly patients with MCL. Early data indicate a high response rate. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mantle Cell Lymphoma Mimicking Rectal Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Engin Kelkitli ◽  
Hilmi Atay ◽  
Levent Yıldız ◽  
Ahmet Bektaş ◽  
Mehmet Turgut
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Rectal Carcinoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Extranodal Involvement ◽  
Non Hodgkin Lymphoma ◽  
Rectal Involvement ◽  
Mantle Cell ◽  
Rectal Mass

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma. After the (11;14) translocation was identified as its constant finding in 1992, MCL was recognized as a separate subgroup of non-Hodgkin lymphoma (NHL). In MCL, extranodal involvement may be observed in the bone marrow, the spleen, the liver, and the gastrointestinal system (GIS). Cases of MCL that present with a massive and solitary rectal mass are rare in the literature. In this case report, our aim was to present an MCL patient with a rarely observed solitary rectal involvement mimicking rectal carcinoma and to discuss treatment options for this patient.

scholarly journals An open‐label phase 2 trial of entospletinib in indolent non‐Hodgkin lymphoma and mantle cell lymphoma

2018 ◽  
Vol 184 (2) ◽  
pp. 215-222 ◽  
Author(s):  
David J. Andorsky ◽  
Kathryn S. Kolibaba ◽  
Sarit Assouline ◽  
Andres Forero‐Torres ◽  
Vicky Jones ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Phase 2 ◽  
Open Label ◽  
Non Hodgkin Lymphoma ◽  
Phase 2 Trial ◽  
Mantle Cell ◽  
Open Label Phase

scholarly journals Mantle Cell Lymphoma Presenting as a Subcutaneous Mass of the Right Leg

2020 ◽  
Vol 13 (2) ◽  
pp. 774-782
Author(s):  
Drew A. Fajardo ◽  
Joel France ◽  
Bogna I. Targonska ◽  
H. Bobby Kahlon ◽  
Max J. Coppes
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell ◽  
History Of ◽  
Subcutaneous Mass ◽  
Systemic Symptoms ◽  
The Right

Mantle cell lymphoma (MCL) is a relatively rare B-cell non-Hodgkin lymphoma, typically presenting with extensive lymphadenopathy, bone marrow involvement, and splenomegaly. Extranodal sites can also be involved. We discuss a 73-year-old man whose MCL presented with a 6-month history of a subdermal mass of the right upper thigh and no systemic symptoms.

scholarly journals The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2807-2812 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Julie M. Vose ◽  
Jennifer L. Kelly ◽  
Faith Young ◽  
Steven H. Bernstein ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Objective Response ◽  
Synergistic Activity ◽  
Significant Activity ◽  
Serious Adverse Events ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell

AbstractGiven the significant activity and tolerability of bendamustine, rituximab, and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma, and laboratory studies suggesting synergistic activity, we conducted a multicenter phase 2 study of the bendamustine/bortezomib/rituximab combination. Patients with relapsed or refractory indolent and mantle cell lymphoma with adequate organ function were treated with bendamustine 90 mg/m2 days 1 and 4; rituximab 375 mg/m2 day 1, and bortezomib 1.3 mg/m2 days 1, 4, 8, 11. Six 28-day cycles were planned. Thirty patients (7 with mantle cell lymphoma) were enrolled and treated. Eight patients experienced serious adverse events, including one event of grade 5 sepsis. Common nonhematologic adverse events were generally grade 1 or grade 2 and included nausea (50%), neuropathy (47%), fatigue (47%), constipation (40%), and fever (40%). Of 29 patients evaluable for efficacy, 24 (83%) achieved an objective response (including 15 with complete response). With median follow-up of 24 months, 2-year progression-free survival is 47% (95% confidence interval, 25%-69%). On the basis of these promising results, the US cooperative groups have initiated randomized trials to evaluate this regimen in follicular and mantle cell lymphoma. This trial was registered at www.clinicaltrials.gov as #NCT00547534.

Multimodal Dose Dense Therapy for Mantle Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1163-1163
Author(s):  
Sam O. Wanko ◽  
Jon P. Gocherman ◽  
Joseph O. Moore ◽  
Carlos Decastro ◽  
Robert Prosnitz ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Mantle Cell ◽  
Dose Dense

Abstract BACKGROUND: Mantle cell lymphoma (MCL) typically has a poor outcome with overall survival of only 3–4 years. Higher treatment response and event-free survival has been demonstrated with aggressive high dose chemotherapy followed by autologous hematopoietic stem cell support, though long term cure rates remain unclear(Dreger P. Hematol J. 2000;vol.2). Modest response rates have also been reported with the monoclonal antibody (MoAb) rituximab and ALEMTUZUMAB (Foran, JM. JCO 2000; vol. 2. Faderl S. Blood 2003; vol. 9). We therefore combined dose-dense therapy with MoAbs to explore response rate and event free survival (EFS) in mantle cell lymphoma. The strength of this trial design is ability to follow all patients from induction chemotherapy through high dose therapy and transplant in order to gauge clinical outcome on all enrolled patients, not just the subpopulation who is able to proceed to high dose therapy. PATIENTS AND METHODS: Induction therapy consisted of 1 cycle of high dose cytarabine (3gm/m2 IV over 1 hour Q12H for 8 doses), mitoxantrone (10mg/m2 daily for 3 days), and ALEMTUZUMAB 30mg IV 3 times a week for 6 weeks with growth factor support. All responding patients were mobilized with cyclophosphamide 4gm/m2 and G-CSF 10 mcg/kg/day and/or bone marrow harvest. The transplant preparative regimen was carmustine 15mg/kg over 2 hours day -6, etoposide 60mg/kg over 4 hours day -4, and cyclophosphamide 100mg/kg over 2 hours day -2 followed by autologous reinfusion on day zero. Consolidation was given with rituximab 375mg/m2 weekly for 4 doses at 6 weeks and 6 months post transplant. RESULT: 9 patients with advanced disease (7 stage IV, 1 stage III, 1 stage IIA) and median age of 60 (48 – 65 years) have been accrued and treated since February 2003. Four were newly diagnosed and 5 had relapsed/refractory disease. Seventy eight percent (7/9) had complete response and 22% (2/9) had partial response (PR) following induction therapy. One patient had severe infection after induction and was unable to proceed to transplant. Another had constitutional decline preventing further therapy and each died within 4 months of withdrawal from the protocol. Both had relapse/refractory disease at accrual. The remaining 7 patients proceeded to the transplant phase. With a median follow-up of 7 months (range 3–16 months), all 7 patients remain in CR for 1 –16 months. Significant induction therapy toxicity included neutropenia in all 9 patients with average duration of 10.7 days, non-disseminated CMV reactivation in 44% of patients, one overwhelming fungal infection, and one patient with delay in engraftment. Figure Figure CONCLUSION: Our preliminary data show a high induction and transplant phase completion rate, manageable toxicity, and excellent overall response rate in this group of elderly patients with advanced disease. Larger numbers of patients and longer follow-up is needed to confirm these promising results.

Anti-Tumor Activity of Single-Agent CCI-779 for Relapsed Mantle Cell Lymphoma: A Phase II Trial in the North Central Cancer Treatment Group.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 129-129 ◽  
Author(s):  
Thomas Witzig ◽  
Susan Geyer ◽  
Irene Ghobrial ◽  
David Inwards ◽  
Rafael Fonseca ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Median Time ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Pi3k Pathway ◽  
Mantle Cell ◽  
Grade 3 ◽  
Anti Tumor Activity

Abstract Purpose: Mantle cell lymphoma (MCL) is characterized by a t(11;14) resulting in overexpression of cyclin D1, a member of the phosphatidylinosital 3 kinase (PI3K) pathway. This study tested whether CCI-779, which inhibits the PI3K pathway at the level of the mammalian target of rapamycin (mTOR) could produce tumor responses in patients (pts) with MCL. Patients and Methods: Eligible pts had biopsy-proven, cyclin D1 positive MCL and had relapsed or were refractory to therapy. Pts received CCI-779 250 mg IV every week as a single agent. Pts were re-staged after 1 cycle (4 doses) and every 3 cycles thereafter. Pts with a tumor response after 6 cycles were eligible to continue drug for a total of 12 cycles or 2 cycles after complete remission (CR) and then were observed. Results: Thirty-five pts were enrolled and evaluable for toxicity; 1 patient had MCL by histology but was cyclin D1 negative and ineligible for efficacy evaluation. The median age was 70 years (range, 38–89), 91% were stage 4, and 69% had ≥ 2 extranodal sites. Pts had received a median of 3 prior therapies (range, 1–11) and 54% were refractory to their last treatment. The overall response rate was 38% (13/34) with 1 CR (3%) and 12 PRs (35%), surpassing the pre-defined criteria for a promising agent. Responses tended to occur rapidly with median time to response of 1 month (range, 1–8). To date, 26 patients have progressed, with a median time-to-progression of 6.8 months (95% CI: 3.8 – 9.7). Median duration of response for the 13 responders was 5.7 months (95% CI: 5.2 – 13.2). Overall, 32 out of 35 patients who received treatment had grade 3 or 4 toxicity. The most common toxicities were hematologic with grade 3 (n=24) or grade 4 (n=4). Thrombocytopenia was the most frequent grade 3/4 toxicity (n=25) and the largest cause of dose-reductions, although counts typically recovered within one week. Only 4 patients could tolerate sustained 250 mg per week throughout their treatment (including one who went on to alternate treatment after 1 cycle) and the median dose/month was 175 mg. Conclusions: Single-agent CCI-779 has substantial anti-tumor activity in relapsed MCL. This study demonstrates that agents, which selectively target cellular pathways dysregulated in MCL cells can produce therapeutic benefit. The high response rate warrants further studies of this agent in MCL, but the high incidence of hematologic toxicity suggests that a lower dose should be explored. CCI-779 at 25mg is currently being evaluated in MCL through an NCCTG trial

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