scholarly journals Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy

Cancer ◽  
2018 ◽  
Vol 124 (11) ◽  
pp. 2306-2315 ◽  
Author(s):  
I. Brian Greenwell ◽  
Ashley D. Staton ◽  
Michael J. Lee ◽  
Jeffrey M. Switchenko ◽  
Debra F. Saxe ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Cell Lymphoma ◽  
Poor Response ◽  
Complex Karyotype ◽  
Mantle Cell

EARLY PROGRESSION OF MANTLE CELL LYMPHOMA DEPICTS A HIGH-RISK DISEASE WITH POOR RESPONSE TO SUBSEQUENT THERAPIES AND A DISMAL OUTCOME

2019 ◽  
Vol 37 ◽  
pp. 242-242
Author(s):  
C.W. Eskelund ◽  
A. Kolstad ◽  
I. Glimelius ◽  
R. Räty ◽  
L.R. Gjerdrum ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Poor Response ◽  
High Risk Disease ◽  
Mantle Cell ◽  
Early Progression

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.

scholarly journals Phase II trial of R-CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601

2015 ◽  
Vol 172 (2) ◽  
pp. 208-218 ◽  
Author(s):  
Brian G. Till ◽  
Hongli Li ◽  
Steven H. Bernstein ◽  
Richard I. Fisher ◽  
W. Richard Burack ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Induction Therapy ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
Newly Diagnosed ◽  
Mantle Cell

Association of complex karyotype with inferior progression-free and overall survival in mantle cell lymphoma.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 7565-7565 ◽  
Author(s):  
I Brian Greenwell ◽  
Ashley Darnell Staton ◽  
Michael J Lee ◽  
Jeffrey M. Switchenko ◽  
Joseph J. Maly ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Complex Karyotype ◽  
Mantle Cell

R-CHOP Versus R-FC Followed by Maintenance with Rituximab Versus Interferon-Alfa: Outcome of the First Randomized Trial for Elderly Patients with Mantle Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 439-439 ◽  
Author(s):  
J.C. Kluin-Nelemans ◽  
E. Hoster ◽  
J. Walewski ◽  
S. Stilgenbauer ◽  
C. H. Geisler ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Interferon Alfa ◽  
Rituximab Maintenance ◽  
Remission Duration ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 439 Introduction. The prognosis of elderly patients with mantle cell lymphoma (MCL) is poor. Despite R-CHOP, only low rates of complete remissions (CR) are obtained and almost all patients relapse. Median overall survival (OS) used to be far below 5 years. Within the European MCL Network we performed a randomized intergroup trial to investigate both whether a fludarabine-containing induction regimen could improve the CR-rate, and whether maintenance with rituximab could prolong remission duration. Methods. Patients with stage II-IV MCL >60 yrs not eligible for high-dose therapy were randomized between either 8 × R-CHOP-21 (day 1: rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, max 2 mg and day 1–5 prednisone 100 mg) or 6 × R-FC-28 (rituximab 375 mg/m2 day 1, fludarabine 30 mg/m2 + cyclophosphamide 250 mg/m2, both iv day 1–3). Responding (CR, CRu, PR) patients underwent a second randomization between maintenance with rituximab one dose every 2 months or interferon-alfa (IFN; regular IFN weekly 3×3 MIU or pegylated IFN 1×1 μg/kg), both given until progression. First randomisation for induction therapy - R-CHOP vs R-FC: Between Jan 2004 and Oct 2010, 560 patients were entered; 457 were evaluable for response to induction. Median age was 70 yrs, 70% male, 83% stage IV, 41% intermediate and 50% high-risk MIPI. Whereas CR rates after R-FC and R-CHOP were similar (38 vs 34% CR, 52 vs 50% CR/CRu, respectively), the overall response rate was lower after R-FC (78% vs 87%; p=0.0508). Progressive disease was more frequent during R-FC (15% vs 5%). Of note, median OS was significantly inferior after R-FC (40 vs 64 months; p=0.0072). More patients died after initial progression (14% vs 4%) or in first remission (11% vs 3%) in the R-FC arm compared to R-CHOP. Hematologic grade 3–4 toxicities were more frequent during R-FC, especially thrombocytopenia (40% vs 17%). Non-hematologic grade 3–4 toxicity was rare (below 7% each), except neutropenic fever (12% R-FC; 18% R-CHOP) and infections (16% R-FC; 14% R-CHOP). Second randomisation for maintenance therapy - Interferon-alpha vs Rituximab: From the responding patients, 310 underwent the second randomization. Sixty-one percent of patients had a CR/CRu upon induction therapy. Fifty-eight percent had received R-CHOP induction. Rituximab maintenance almost doubled the remission duration compared with IFN (at 4-yrs 57% vs 26% in remission; HR 0.54, 0.35–0.87; p=0.0109). Overall survival did not differ between both maintenance arms (p=0.17). However, the subcohort of R-CHOP-treated patients showed a significant advantage after rituximab maintenance (4-yr OS 87% vs 57% after IFN; p=0.0061). Hematologic grade 3–4 toxicity was higher in the IFN arm (leukocytopenia 33% vs 16%; thrombocytopenia 15% vs 6%); non-hematologic grade 3–4 toxicity was rare, except for infections (8% IFN; 7% rituximab). R-FC followed by rituximab resulted in the highest infection rate (CTC grades 1–4: 50%), whereas all other combinations (R-CHOP followed by rituximab or IFN, and R-FC followed by IFN) ranged between 25–35%. Patients in CR/CRu or PR after induction who did not receive any maintenance for various reasons, mainly based upon patient's decisions or ongoing cytopenia after induction (n = 104), had a poor outcome (median remission duration 18 months). Conclusions. Induction therapy with R-FC is discouraged for elderly patients with MCL, whereas R-CHOP induction followed by rituximab maintenance should be considered the new standard for elderly MCL patients, to which new regimens need to be compared. Disclosures: Off Label Use: rituximab maintenance for mantle cell lymphoma. Geisler:Roche: Consultancy, Research Funding; Celgene: Consultancy; GSK: Consultancy. Tilly:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hiddemann:Roche Pharma: Honoraria, Research Funding. Dreyling:Roche: Research Funding, Scientific advisory board, Speakers Bureau.

Mature Results From ECOG Study E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for Previously Untreated Mantle Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 153-153 ◽  
Author(s):  
Brad S. Kahl ◽  
Hailun Li ◽  
Mitchell R Smith ◽  
Randy D. Gascoyne ◽  
David T. Yang ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Treatment Plan ◽  
Induction Treatment ◽  
High Dose ◽  
Group Setting ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 153 Introduction Modified R-hyperCVAD is a well-tolerated induction regimen with a high response rate in MCL. We hypothesized that the incorporation of bortezomib (Velcadea) into this regimen would enhance the complete response rates. We further hypothesized that the addition of maintenance rituximab (MR) would improve remission duration. The new regimen, VcR-CVAD with MR, was tested for safety and efficacy in the Eastern Cooperative Oncology Group. Methods Eligible patients had histologically confirmed, previously untreated MCL, PS 0–2, and adequate end organ function. The treatment plan included: bortezomib 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs × 6 doses days 1–3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1–2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1–4. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF support. Patients achieving SD, PR, or CR received MR administered as 4 weekly treatments every 6 months for 2 years (protocol therapy). Patients could elect to receive high dose chemotherapy and autologous stem cell transplantation (SCT) off protocol rather than MR. The primary endpoint of the trial was the CR rate, defined as PET-negative, marrow-negative, to VcR-CVAD induction therapy. Results Seventy-five eligible patients were enrolled between 5/07 and 10/08. Baseline characteristics include median age 62 (40–76), 58M:17F, 92% stage III/IV, and 40% with elevated LDH. MIPI risk distribution included 37% low, 36% intermediate, 19% high, 8% unknown. Sixty-eight patients (91%) completed VcR-CVAD induction therapy. Reasons for treatment discontinuation included PD (1), toxicity (4), and patient preference (2). The ORR was 97% (73/75), CR rate 68% (51/75) and PR rate 29% (22/75). Of the 22 PR patients, 11 were so coded due to no bone marrow evaluation and/or PET imaging post therapy. The CR rate in the 64 completely restaged patients was 80%. Forty-four patients proceeded to protocol planned MR while 22 patients received SCT consolidation off protocol. With a median follow up of 3.6 years, the 3-yr PFS for the MR cohort (n = 44) and entire cohort (n = 75) are 73% and 74%, respectively. OS at 3-yrs is 88%, with no difference between MR and SCT patients. The major toxicity of the induction treatment regimen was expected myelosuppression. Grade 3–4 non-hematologic toxicities were rare. No patients developed grade 3–4 neuropathy. There were no serious toxicities during MR. There were no treatment related deaths. Conclusion The VcR-CVAD induction produced high overall OR (97%) and CR rates (68%) in a representative MCL patient population treated in a cooperative group setting. The 3-yr PFS (74%) and OS (88%) are highly encouraging. Remissions in patients receiving MR were as durable as patients receiving SCT consolidation. The value of bortezomib, when added to conventional chemotherapy, is currently being tested in a randomized intergroup trial (E1411). Disclosures: Kahl: Genentech: Consultancy, Research Funding; Roche: Consultancy; Millennium: Consultancy, Research Funding. Off Label Use: Bortezomib as frontline treatment of mantle cell lymphoma. Smith:Millennium: Research Funding. Advani:Genentech: Research Funding. Horning:Genentech: Employment; Roche: Equity Ownership.

Complex Karyotype Is Associated With Aggressive Disease and Shortened Progression-Free Survival in Patients With Newly Diagnosed Mantle Cell Lymphoma

2015 ◽  
Vol 15 (5) ◽  
pp. 278-285.e1 ◽  
Author(s):  
Jonathon B. Cohen ◽  
Amy S. Ruppert ◽  
Nyla A. Heerema ◽  
Leslie A. Andritsos ◽  
Jeffrey A. Jones ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Complex Karyotype ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Aggressive Disease ◽  
Mantle Cell

TP53 Mutation and Complex Karyotype Portends a Dismal Prognosis in Patients With Mantle Cell Lymphoma

2018 ◽  
Vol 18 (11) ◽  
pp. 762-768 ◽  
Author(s):  
Aleš Obr ◽  
Vít Procházka ◽  
Andrea Jirkuvová ◽  
Helena Urbánková ◽  
Eva Kriegova ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Tp53 Mutation ◽  
Cell Lymphoma ◽  
Complex Karyotype ◽  
Dismal Prognosis ◽  
Mantle Cell
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